MR Probes I
Exhibit Hall 2-3                    Monday 14:00-16:00          Computer 1

14:00         3114.     A CLT1 Peptide Targeted Nanoglobular Contrast Agent for Cancer Molecular Imaging with MRI

Mingqian Tan1, Xueming Wu1, Furong Ye1, Eun-Kee Jeong2, Zheng-Rong Lu1

1Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA; 2Department of Radiology, University of Utah, Salt Lake City, UT, USA

A CLT1 peptide-targeted nanoglobular MRI contrast agent with a compact and precisely defined molecular architecture was designed and prepared via click chemistry to molecular imaging of fibrin-fibronectin complexes in tumor tissue. The peptide-targeted contrast agent was characterized by HPLC, MALDI-TOF mass spectrometry, amino acid analysis, and ICP-OES. The targeted contrast agent resulted in more significant tumor enhancement than the non-targeted agent, which shows a potential for specific cancer molecular imaging with MRI.

14:30         3115.     In Vivo Targeting of α ν β 3-Specific Dual-Modality Micellar Nanoprobes

Chase W. Kessinger1, Osamu Togao1, Chalermchai Khemtong1, Masaya Takahashi1, Jinming Gao1

1UT Southwestern Medical Center, Dallas, TX, USA

Here we report an α vb3-specific dual-imaging magnetofluorescent nanoprobes that allowed detection of angiogenic tumor vessels by both fluorescent and magnetic resonance imaging. The α vb 3-targeting specificity and temporal tumor accumulation profiles were demonstrated in a human lung tumor xenograft model in nude mice in vivo.

15:00         3116.     A Boron/Gd/LDL Adduct for Imaging-Guided Neutron Capture Therapy

Simonetta Geninatti1, Diego Alberti, Antonio Coppino2, Ibolya Szabo2, Annamaria Deagostino3, Paolo Venturello2, Silvio Aime2

1University of Torino, Torino, Italy; 2University of Torino, Italy; 3University of torino, Italy

LDLs act as efficient carriers for the delivery of a new imaging probe containing Gd and Boron. It follows that imaging guided Boron Neutron Capture Therapy appears possible as, from the signal enhancement generated by the paramagnetic Gd(III) complexes, we access to the key information that the 10B concentration threshold has been reached.

15:30         3117.     Gd(III)-Based Probes for MR Imaging of Exofacial Protein Thiols

Giuseppe Digilio1, Valeria Menchise2, Valeria Catanzaro3, Franco Fedeli3, Roberta Napolitano3, Concetta Gringeri1, Eliana Gianolio3, Silvio Aime3

1DISAV, University of Eastern Piedmont, Alessandria, AL, Italy; 2IBB, CNR, Italy; 3Chemistry IFM, University of Torino, Italy

A new Gd(III)-based contrast agent (CA) targeting the exofacial protein thiols is presented. Uptake experiments with cultured K562 cells show that the CA is efficiently bound to surface protein thiols and at least partially internalized. The amount of uptaken Gd(III) per cell is well above the threshold for visualization by MRI.

 
Exhibit Hall 2-3                    Tuesday 13:30-15:30          Computer 1

13:30         3118.     In Vivo MR Imaging of Renal Ischemia Reperfusion Injury in Mice Using Microparticles of Iron Oxide Targeting VCAM-1

Jurgen E. Schneider1, Asim M. Akhtar1, Hannah Barnes1, Stephanie Baker2, Janet E. Digby1, Martina A. McAteer1, Kathryn Wood2, Robin P. Choudhury1

1Cardiovascular Medicine, University of Oxford, Oxford, Oxon, UK; 2Nuffield Department of Surgery, University of Oxford, Oxford, Oxon, UK

Ischemia/reperfusion injury (IRI) is an important cause of tissue damage in vascular syndromes of the heart, brain and kidney, but sensitive tools to image ischemic injury in vivo are lacking. Our study demonstrated that (a) antibody-conjugated microparticles of iron oxide (MPIO) targeting VCAM-1 enabled molecular magnetic resonance imaging of endothelial activation in mouse renal IRI; (b) the retained MPIO were readily quantifiable from the MR images. Our approach provides a platform for non-invasive detection of IRI in the kidney and potentially other organs.

14:00         3119.     Imaging of Neuroinflammation with an ICAM-1 Specific Paramagnetic and Fluorescent Nanoparticle

Lisette H. Deddens1, Matti M. Van Schooneveld2, Susanne M A Van der Pol3, Rolf Koole2, Helga E. De Vries3, Willem J M Mulder4, Rick M. Dijkhuizen1

1Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands; 2Condensed Matter and Interfaces, Utrecht University, Utrecht, Netherlands; 3Molecular Cell Biology and Immunology, VU Medical Center, Amsterdam, Netherlands; 4Translational and Molecular Imaging Institute and Imaging Science Laboratories, Mount Sinai School of Medicine, New York, USA

Neuroinflammation plays a critical role in various brain disorders. Specific multimodal imaging probes may shed new light on the explicit involvement of distinct neuroinflammatory events, which could make way for new or improved anti-inflammatory treatment strategies. This study reports on the assembly and application of a probe consisting of fluorescent quantum dots in silica with a paramagnetic lipid coating targeted to ICAM-1. The probe is biocompatible, specifically taken up by inflamed mouse cerebrovascular endothelial cells and detectable with MRI. It may provide a useful tool for in vivo molecular MR and optical imaging of upregulated cell adhesion molecules after neuroinflammation.

14:30         3120.     In Vivo Visualization of Cells Marked with Ultra-Small Gd2O3 Nanoparticles, Using a 1.5 T Clinical System and the Chick Embryo Model

Marc-Andre Fortin1, Luc Faucher1, Andrée-Anne Guay-Bégin2, Eric Petitclerc3, Yves Gossuin4, Annelie Lindström5

1Materials Engineering, Laval University and Centre hospitalier universitaire de Quebec (CHUQ), Quebec City, Quebec, Canada; 2Materials Engineering, Laval University and Centre hospitalier universitaire de Quebec (CHUQ), Quebec City, Quebec , Canada; 3Centre hospitalier universitaire de Québec (CHUQ), Laval University, Quebec City, Quebec, Canada; 4University of Mons-Hainaut, Belgium; 5Linköping University, Sweden

Ultra-small gadolinium oxide nanoparticles (US-Gd2O3) have recently emerged as a promising alternative to iron oxide nanoparticles for cell staining. Used with common T1-weighted imaging procedures, they provide positive contrast and high signal. In this work we present the first cell marking and visualisation study performed in-vivo with this new type of contrast agent. Glioma cancer cells were incubated with US-Gd2O3 and then implanted at the surface of chick chorioallantoic membrane (CAM). Clusters of marked cells implanted in this vascularized model system, were clearly visible days after the implantation. T1-weighted images are free of T2/T2* image artefacts characteristic of iron oxide staining.

15:00         3121.     MR Molecular Imaging of Cerebrovascular Amyloid Deposits

Kristi Lynn Hultman1, Jessica L. Lack1, Thomas M. Wengenack2, Geoffry L. Curran2, Gregory M. Preboske3, Ramakrishnan Muthu2, Michael Garwood4, Clifford R. Jack Jr3, Joseph F. Poduslo2

1Molecular Neurobiology, Mayo Clinic College of Medicine, Rochester , MN, USA; 2Molecular Neurobiology, Mayo Clinic College of Medicine, Rochester, MN, USA; 3Radiology, Mayo Clinic College of Medicine, Rochester, MN, USA; 4Center for Magnetic Resonance Research, University of Minnesota Medical School, Minneapolis, MN, USA

Cerebral amyloid angiopathy(CAA) and Alzheimer’s disease(AD) are characterized by accumulation of amyloid-β peptides in the brain. The development of targeted nanoparticle(MION) contrast agents to distinguish these diseases using MR imaging would aid in their diagnosis and treatment. Here we report the development of pF(ab)´ 24.1 MIONs for use as an MRI probe to identify cerebrovascular amyloid in ex-vivo mouse brains with MRI. We were able to demonstrate that the pF(ab)´ 24.1-MION conjugate bound to cerebrovascular amyloid in isolated blood vessels from APP/PS1 mouse brain. In T1-weighted images of ex-vivo APP/PS1 mouse brain, dark contrast spots suggest pF(ab)´ 24.1-MIONs binding to cerebrovascular amyloid.

 
Exhibit Hall 2-3                    Wednesday 13:30-15:30          Computer 1

13:30         3122.     MRI-Contrast Agents for Detection of Bacterial Infection

Ania Warczyk1,2, Anatoliy Popov2, Stephen Pickup2, Ari Goldberg2, E. James Delikatny2

1Pharmacology, University of Pennsylvania, Philadelphia, PA, USA; 2Radiology, University of Pennsylvania, Philadelphia, PA, USA

We report two MRI-compatible gadolinium contrast agents that selectively bind bacterial cell membranes allowing for the detection of bacteria with high sensitivity and specificity. The compounds combine a macrocyclic DOTA chelator linked to a moiety that binds bacterial surface lipids with high affinity. Incubation with the targeted contrast agents is shown to significantly increase R1 relaxation rates in cultures of E. coli, in contrast to conventional gadolinium contrast agents that can easily be washed out. The ability to noninvasively identify pathogenic bacterial sources would potentially aid in the diagnosis and treatment of systemic bacteremia.

14:00         3123.     Efficient Intracellular Delivery of an MR Imaging Probe by a Novel Cell Penetrating Peptide

Joern Engelmann1, Deepti Jha1, Ritu Mishra1, Karl-Heinz Wiesmueller2, Kamil Ugurbil1,3

1High Field MR Center, Max-Planck-Institute for Biological Cybernetics, Tuebingen, Germany; 2EMC microcollections GmbH, Tuebingen, Germany; 3Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, MN, USA

A novel cell penetrating peptide (CyLoP-1) was obtained by structure activity relationship studies. It exhibited efficient transport across the cell membrane and distribution in the entire cytosol as well. These distinctive properties were only slightly influenced by the coupling of Gd-DOTA. This conjugate was slightly less internalized into 3T3 fibroblasts, but the cellular distribution was retained. MR studies on labeled cells revealed an exceptional high contrast enhancement in T1-weighted images. These results demonstrate its potential to be used for efficient transmembrane delivery of imaging agents and as vector for probes specifically targeted to cytosolic constituent.

14:30         3124.     Multimodality Investigation of High Density Lipoprotein Action in Atherosclerosis

Torjus Skajaa1,2, David P. Cormode1, Peter Jarzyna1, Alessandra Barazza3, Edward A. Fisher3, Ronald E. Gordon4, Zahi A. Fayad1, Willem J.M. Mulder1

1Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, NY, USA; 2Faculty of Health Sciences, Aarhus, Denmark; 3School of Medicine, New York University, New York, NY, USA; 4Department of Pathology, Mount Sinai School of Medicine, New York, NY, USA

We here report a multimodal investigation of the action of high density lipoprotein (HDL) in atherosclerosis using a HDL mimicking iron oxide nanoparticle. These particles are detectable by MRI, optical techniques and transmission electron microscopy, allowing their visualization at the anatomical, cellular and sub-cellular level. The HDL nanoparticles were applied in vitro and on atherosclerotic and wild type mice in vivo and successfully enabled us to study lipoprotein function.

15:00         3125.     In Vivo Monitoring of Liposomal Encapsulated SiRNA Delivery to Tumours

Gavin Kenny1, Nazila Kamaly1,2, Tammy Kalber1, Andrew D. Miller3, Jimmy Bell1

1Metabolic and Molecular Imaging Group, Imaging Sciences Department, MRC Clinical Sciences Centre, Hammersmith Hospital, Imperial College, London, UK; 2Imperial College Genetic Therapies Centre, Department of Chemistry, Imperial College , London, UK; 3Imperial College Genetic Therapies Centre, Department of Chemistry, Imperial College, London, UK

The aim of this study was to monitor liposomal encapsulated siRNA delivery to tumours in vivo using MR and optical imaging techniques. The liposomes were formulated to include lipids containing MR and optical labels. The siRNA was labelled with FITC to confirm delivery by the liposome to the tumour. The siRNA-liposome was found to reduce T1 significantly at 16 hours post dose and liposome accumulation in the tumour was confirmed by histology. These results suggest that liposomal encapsulated siRNA can be used as a therapeutic delivery method with MR and optical techniques to monitor delivery and efficacy.

 
Exhibit Hall 2-3                    Thursday 13:30-15:30          Computer 1

13:30         3126.     Development of Novel Intravascular MRI Contrast Agents Using Gadolinium Chelates

Chang-Tong Yang1, Krisada Kittigowittana2, Bingwen Zheng1, Kai-Hsiang Chuang1, Roderick W. Bates2, Xavier Golay1

1Laboratory of Molecular Imaging, Singapore Bio-Imaging Consortium, Agency for Science, Technology and Research, Singapore, Singapore; 2Division of Chemistry and Biological Chemistry, School of Ohysical and Mathematical Sciences, Nanyang Technological University, Singapore

We developed a new class of oligomer-based MRI contrast agents (CAs) by incorporating multi-gadolinium complexes into peptides of controlled length and structure in order to overcome the limitations of both low molecular weight and polymeric macromolecular Gd complexes. Two CAs of GdDO3A conjugated amino acids building blocks derived from glutamic acid and lysine have been synthesized. The T1 relaxivities of two CAs measured at 9.4T are higher than that of clinically used Gd-DTPA and Gd-DOTA. In vivo imaging in rat demonstrated considerable signal enhancement and long blood half-life using GdDO3A-lysine.

14:00         3127.     High T1-Relaxivity Nanoparticles for Target Labeling of Ovarian Cancer

Sergey Magnitsky1, Anatoliy V. Popov1, Chunsheng Li2, Jennifer Swails2, Stephen Pickup1, George Coukos2, Jerry D. Glickson1

1Radiology, The University of Pennsylvania, Philadelphia, PA, USA; 2Department of Obstetrics and Gynecology, The University of Pennsylvania, Philadelphia, PA, USA

We developed a method for synthesizing targeted nanoparticles with high longitudinal relaxivity for MRI detection of ovarian cancer. We have incorporated Gd-DTPA-DSA and scFv-fragments of tumor specific antibodies into lipid shells of 200 nm diameter perfluorocarbon nanoparticles. The particles exhibit a longitudinal relaxivity of 28.2 mmol-1sec-1 at 18°C, 9.4 T per Gd and a high affinity for human ovarian cancer cells. These studies demonstrate the potential application of these contrast agents for in vivo application.

14:30         3128.     Development of Spontaneously Disassembling Dendrimers as a Platform Technology for PARACEST MRI Contrast Agents

Yuguo Li1, Mark D. Pagel1

1Arizona Cancer Center, University of Arizona, Tucson, AZ, USA

Spontaneously disassembling dendrimers are nanocarriers can carry high payloads of chemotherapies to pathological tissues, and then rapidly release the chemotherapies during enzyme-triggered spontaneous disassembly of the dendrimers. To investigate whether a spontaneously disassembling systems can generate a PARACEST effect, a non-dendritic model system was shown to generate a PARACEST effect after enzyme-triggered spontaneous disassembly. To investigate the translation of this approach to a dendritic system, the G0 core of a spontaneously disassembling dendrimer was designed and synthesized. This platform technology is being refined for PARACEST MRI.

15:00         3129.     Reconstituted High Density Lipoprotein Nanoparticles for Multimodality Molecular Imaging of Tumors

Wei Chen1, Peter Jarzyna1, Geralda A.F. von Tilborg2, Van anh Nguyen3, Gwendalyn J. Randolph3, Edward A. Fisher4, Willem J.M. Mulder1, Zahi A. Fayad1

1Translational and Molecular Imaging Institute, Imaging Science Laboratories, Mt. Sinai School of Medicine, New York, NY, USA; 2Technische Universiteit Eindhoven, Netherlands; 3Department of Gene and Cell Medicine, Mt. Sinai School of Medicine, New York, NY, USA; 4Marc and Ruti Bell Vascular Biology and Disease Program, NYU School of Medicine, New York, NY, USA

The uptake of reconstituted high density lipoprotein (rHDL) and rHDL functionalized with α;vb3-specific RGD peptides (rHDL-RGD) were examined in vitro using cultured macrophages and endothelial cells. It was observed that rHDL was phagocytosed by macrophages, while α;vb3-specific rHDL-RGD nanoparticles were preferentially taken up by endothelial cells. The uptake of both particles in mouse tumors was evaluated in vivo using NIR and MR imaging. Both rHDL and rHDL-RGD accumulated in tumors, be it with different accumulation kinetics. In conclusion we have shown the versatility of the rHDL nanoparticle platform and its potential for multimodality imaging of tumor associated processes.

 


 
MR Probes II
Exhibit Hall 2-3                    Monday 14:00-16:00          Computer 2

14:00         3130.     In Vivo Evaluation of a New Extracellular Gd(III) Complex Endowed with High Relaxivity for Tumor Detection in Mice

Alessandro Maiocchi1, Fulvio Uggeri1, Alessandro Barge2, Silvio Aime2, Lorenzo Tei3

1Bracco Imaging s.p.a., Colleretto Giacosa, Torino, Italy; 2Università degli Studi di Torino, Torino, Italy; 3Università degli Studi del Piemonte Orientale, Alessandria, Italy

A new extracellular, high relaxivity Gd(III) complex based on a DTPA-like structure was synthesized. It displays a remarkable relaxivity (r1=19 mM-1s-1) that is the result of the occurrence of a large second coordination sphere contribution arising from the extended network of water molecules, hydroxyl containing substituents and the phosponate moiety at the ligand surface. The high hydrophilicity endows this complex with the biodistribution and excretion pathways of the commonly used extracellular Gd(III) agents. The “in vivo” imaging properties of the new agent was assessed by comparing the contrast enhancement induced in tumor lesions of Her-2/neu transgenic mice in respect to ProHance®

14:30         3131.     The Gadonanotubes: A New Paradigm in Low-Field MR Imaging

Jeyarama Subramanian Ananta Naryanan1, Shingo Matsumoto2, James B. Mitchell2, Murali C. Krishna2, Lon J. Wilson1

1Chemistry, Rice University, Houston, TX, USA; 2Radiation Biology, National Institutes of Health, Bethesda, MD, USA

Here, we present a new paradigm called Gadonanotubes (Carbon nanotubes filled internally with gadolinium ions) for low-field contrast-enhanced MR imaging and potential cell-trafficking studies. The Gadonanotubes have shown very high T1 relaxation efficiency (~160 mM-1 s-1) at very low field strength of 15 mT. Even higher efficiency is possible with improvised pulse sequences. In addition, the gadonanotubes have also shown to be very efficient in labeling cells, which could open new pathways for in vivo imaging and cell trafficking studies which are currently restricted at low-fields due to lack of contrast enhancement.

15:00         3132.     Swollen Micelles; a Nanoparticulate Platform for the Delivery of Hydrophobic Agents

Peter Adalbert Jarzyna1, Torjus Skajaa1, David P. Cormode1, Daniel Samber1, Arjan W. Griffioen2, Zahi A. Fayad1, Willem J M Mulder1

1Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York City, NY, USA; 2Research Institute for Growth and Development (GROW), University Hospital Maastricht, Maastricht, Netherlands

We developed a new nanoparticle platform for the delivery of hydrophobic material to tumors that have properties included to enable their visualization with both MRI and optical techniques. The nanoparticle consists of a nanoemulsion preparation with hydrophobically coated iron oxide particles in the oil phase and the NIR fluorescent dye Cy5.5 coupled to the lipid surface. Three formulations with distinct particle sizes of 30, 60 and 94 nm were successfully synthesized and two were applied to a subcutaneous tumor mouse model. Multimodality imaging was performed to demonstrate tumor specificity, to visualize distribution and to determine pharmacokinetics.

15:30         3133.     New Vanadium-Based Magnetic Resonance Imaging Probes Target Glycolytic Tumors

Devkumar Mustafi1, Elizabeth Peng1, Sean Foxley2, Gregory S. Karczmar2, Marta Zamora2, John W. Ejnik3, Heather Martin3

1Biochemistry & Molecular Biology, The University of Chicago, Chicago, IL, USA; 2Radiology, The University of Chicago, Chicago, IL, USA; 3Chemistry, Northern Michigan University, Marquette, MI, USA

Current gadolinium-based MRI contrast agents are non-specific for cancer and quickly wash out of the blood. Non-toxic vanadyl chelates (VCs) interact with intracellular glycolytic enzymes and, therefore, selectively accumulate in highly glycolytic cancer cells. They bind to serum proteins; this increases their blood half-life and results in selective leakage from hyperpermeable tumor vasculature. We have characterized the binding interactions between a VC and albumin. In vitro measurements of VC uptake by tumor and muscle tissues, and in vivo MRI studies, demonstrate that VC is a blood-pool agent that accumulates within cancer cells, thereby preferentially enhancing MR images of rodent tumors.

 
Exhibit Hall 2-3                    Tuesday 13:30-15:30          Computer 2

13:30         3134.     Novel Perfluorocarbon Nanoemulsion for 19F MRI Cell Tracking of Two Cell Populations in Vivo

Jelena M. Janjic1, Deepak K. Kadayakkara1, Lisa K. Pusateri1, Eric T. Ahrens1,2

1Carnegie Mellon University, Pittsburgh, PA, USA; 2Pittsburgh NMR Center for Biomedical Research, Pittsburgh, PA, USA

A novel, non-toxic 19F tracer reagent, perfluorotertbutylether (PFTE) nanoemulsion, suitable for ex vivo cell labeling and in vivo imaging is described. The feasibility of multi-spectral 19F MRI using PFTE and perfluoro-15-crown-5 ether (PCE) to visualize two cell populations in vivo is demonstrated. The development of the new PFTE nanoemulsion opens up the possibility to study immune cell-cell interactions in vivo using MRI.

14:00         3135.     Ferritin Overexpression as a Tool for Detection of Live Cells Transplanted Into Infarcted Heart

Anna Naumova1, Hans Reinecke2, Kelly Stevens3, Jennifer Deem4, Vasily Yarnykh1, Chun Yuan1, Charles Murry2

1Radiology, University of Washington, Seattle, WA, USA; 2Pathology, University of Washington, Seattle, WA, USA; 3Bioengineering, University of Washington, Seattle, WA, USA; 4Center for Cardiovascular Biology, Seattle, WA, USA

We compared efficacy of MRI detection of live cells engrafted to the infarcted mouse heart after labeling by iron oxide particles or after ferritin overexpression. Presence of cellular grafts appeared as dark areas caused by iron oxide particles and by iron accumulation in ferritin. Dead cells labeled with particles showed similar signal voids as live labeled cells; no signal was detected in dead transgenic cells. Ferritin overexpression can be a valuable tool for noninvasive detection of live cells transplanted into the heart. This is the first use of MR imaging for the detection of gene expression in cardiac grafts.

14:30         3136.     Genetic Manipulation of Ferritin for Enhanced MRI Contrast

Tatjana Holand1, Panagiotis G. Kyrtatos2, Andrew Lowe2, Anthony N. Price2, Waseem Qasim1, Mark F. Lythgoe2

1Molecular Immunology, Institute of Child Health, University College London, London, UK; 2Centre for Advanced Biomedical Imaging, Institute of Child Health and Department of Medicine, University College London, London, UK

Iron oxide agents have been widely used to track cells in vivo. However, dilution of MRI contrast agent as cells multiply limits the applicability of this method for long-term monitoring of dividing cell populations. We are developing gene delivery strategies that result in the sustained production of endogenous contrast. We have adopted an approach using lentiviral delivery systems, comparing ferritin heavy and light chain, and an enhanced mutant of the ferritin light chain. These vectors are designed for durable gene expression in haematopoietic cell lineages and would be ideal for tumour modelling studies or tracking of cellular therapies in vivo.

15:00         3137.     19F MRI of Fibroblasts and Neuroblastoma Cells Labeled with Emulsified Perfluoro-15-Crown-5 Ether

Samir Mulla-Osman1, Ute Bommerich2, Johannes Bernarding3

1IBMI, University of Magdeburg, Magdeburg, Sachsen-Anhalt, Germany; 2Leibniz-Institute for Neurobiology, Germany; 3IBMI, University of Magdeburg, Sachsen-Anhalt, Germany

19F-labelled cells provide an important new technique to evaluate in vivo the migration of implanted cells such as in stem cell therapy. 19F-marker substances such as perfluorocarbons (PFC ) have been used for cell tracking based on 19F spectroscopy as well as 19F magnetic resonance imaging (MRI). We present first results of 19F MRI of fibroblasts and neuroblastoma cells labeled with PFCE emulsion. The results of the present study show that the labelling procedure allows a hight transfection of the cells. The concentration of the PFCE emulsion reached high levels and cells can be successfully monitored using 19F-MR Imaging.

 
Exhibit Hall 2-3                    Wednesday 13:30-15:30          Computer 2

13:30         3138.     Development of New, More Sensitive MR-Reporter Genes for Stem Cell Tracking and Gene Therapy Imaging

Letterio Salvatore Politi1, Sara Pizzi1, Anna Cozzi2, Mario Amendola3, Andrea Falini1, Luigi Naldini3, Sonia Levi2, Alessandra Biffi3, Giuseppe Scotti1

1Neuroradiology, San Raffaele Scientific Institute, Milan, Italy; 2Iron Metabolism Unit, San Raffaele Scientific Institute, Milan, Italy; 3HSR-TIGET, San Raffaele Scientific Institute, Milan, Italy

MR-reporter genes might allow sustained and stable intracellular contrast accumulation for long-term stem cell (SC) tracking studies and gene therapy applications. Since sensitivity of previously described MR-reporter genes, such as intracellular ferritin, is low, we are exploiting potentially stronger reporters in combination with late generation lentivirial vectors. A new mutated form of human ferritin L-chain (mhL-Fer) that aggregates and stores great iron quantities was tested and compared to wild type H and L human ferritin chains and human tyrosinase. The mhL-Fer turned out to be the strongest reporter gene and allowed sustained and sensitive detection of SC also at 3T.

14:00         3139.     Potential Application of Hyaluronic Acid in MR Imaging

Wenlian Zhu1, Dmitri Artemov1

1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA

CD44 is a recognized target in caner therapy. Here we attempted to use hyaluronic acid (hyaluronan or HA), a major CD44 ligand as a probe to access the CD44 status of breast cancer cells. We also investigated the possibility of using HA gadolinium conjugate as a blood pool MR contrast agent. Preliminary results demonstrated the potential of HA as a CD44 targeting moiety as well as a macromolecular contrast agent carrier.

14:30         3140.     Protein Cages Filled with Gadolium Containing Branched Polymers

Lars Liepold1, Joseph Frank2, Mark Young3, Trevor Douglas1

1Chemistry and Biochemistry, Montana State University, Bozeman, MT, USA; 2Diagnostic Radiology Research, National Institutes of Health, Bethesda, MD, USA; 3Plant Sciences, Montana State University, Bozeman, MT, USA

Here we present a strategy to make highly efficient contrast agents by use of a branched polymer grown in the interior cavity of a protein cage. Gadolinium chelates are covalently linked to the monomers of the branched polymer resulting in 192 Gd3+ ions per cage. Here we report ionic relaxivity values of 20 sec-1 mM-1 and particle relaxivities of 3,821 sec-1 mM-1.

15:00         3141.     Microfabricated Magnetic Microparticles Enable High Contrast MRI Agents

Gary Zabow1,2, Stephen Dodd1, John Moreland2, Alan Koretsky1

1NINDS, NIH, Bethesda, MD, USA; 2Electromagnetics Division, NIST, Boulder, CO, USA

We demonstrate how top-down microfabrication can be used to micromachine magnetic resonance imaging contrast agents with more consistent, and higher, magnetic moments than commonly available chemical synthesized alternatives. Specifically, we describe the microfabrication of gold-coated nickel and iron micro-discs as T2* contrast agents and compare the contrast generated against traditional chemically synthesized MPIO's.

 
Exhibit Hall 2-3                    Thursday 13:30-15:30          Computer 2

13:30         3142.     In Vitro Molecular MRI to Determine Contrast Sensitivity of Gd DTPA Slex Binding to P Selectin

Jessica Hung King  Sang1, Ursula Tuor2,3, Robert Muller4, Tad Foniok2, Philip Barber5

1Department of Health Sciences, University of Calgary, Calgary, Alberta, Canada; 2National Research Council of Canada, Calgary, Alberta, Canada; 3Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada; 4Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, Université de Mons-Hainaut, Mons, Belgium; 5Clinical Neuroscience, University of Calgary, Calgary, Alberta, Canada

Previous magnetic resonance (MR) imaging studies of endothelial activation in the mouse brain post-ischemia have demonstrated rather low contrast sensitivity using a novel contrast probe, Gd-DTPA-B(sLex)A, designed to bind to selectin molecules. Thus, prior knowledge of whether a contrast agent binds with sufficient affinity to its intended molecular target could be a valuable tool. The aim of our study was to develop an assay that would allow us to evaluate the MRI contrast sensitivity and the binding affinity of Gd-DTPA B(sLeX)A for P-selectin in vitro.

14:00         3143.     SPIO-Labeled Cells as an Ffective Vehicle for Tracking GFP Gene Marker with MRI

Zhuoli Zhang1,2, Nicole Mascheri1, Rohan Dharmakumar1, Zhaoyang Fan1, Shengyong Wu2, Debiao Li1, Mark Tengowski2

1Northwestern University, Chicago, IL, USA; 2VirtualScopics Inc., Rochester, NY, USA

Detection of a gene using MRI is hindered by the MR targeting gene technique. Therefore it may be advantageous to image labeled gene expressed cells with SPIO by MRI. The GFP-R3230Ac cell line was incubated using SPIO with at a concentration of 20 µg Fe/mL. SPIO was used to effectively label GFP-cell with no effects on cell function and GFP expression. Labeled GFP-cells were successfully imaged with both fluorescent microscopy and T2*-weighted MRI. Prussian blue staining showed intracellular iron accumulation in the cells. The study demonstrated that the GFP expression and function of cell were not altered by the SPIO labeling process. The technique holds promise for monitoring the temporal and spatial migration of cell with gene marker and likely to enhance the understanding of cell-, gene-based therapeutic strategies.

14:30         3144.     A Novel Iron Oxide Contrast Agent: Nano in Size and Functioning as Micron-Sized Particles

Haosen Zhang1, Chih-Lung Chen2, Wen-Yuan Hsieh2, Hsiu-Hua Huang2, Yi-Shan Lin2, Hsin-Hsin Shen2, Mu-Jen Young2, Wei-Lin Yu2, Ying-Ting Huang2, Qing Ye1, Kevin Hitchens1, Lesley Foley1, Yijen Wu3, Jassy Wang2, Chien Ho1

1Pittsburgh NMR Center for Biomedical Research, Department of Biological Science , Carnegie Mellon University, Pittsburgh, PA, USA; 2Industrial Technology Research Institute, Taiwan; 3Pittsburgh NMR Center for Biomedical Research, Department of Biological Science, Carnegie Mellon University, Pittsburgh, PA, USA

This study was to investigate the labeling efficiency and MRI signal sensitivity of a novel, biodegradable, nano-sized iron oxide particle (ITRI-IOP) with high relaxivity in labeling macrophage, compared with other commercially available iron oxide particles. After being labeled ex vivo with the same amount of iron, Perl¡¦s Pussian Blue staining and MRI show that the nano-sized ITRI-IOP demonstrates comparable labeling efficiency and similar pattern of MRI hypointensity as the commercially available micron-sized particles, and more effective than Feridex. ITRI-IOP could be an effective contrast agent for sensitive cellular MRI.

15:00         3145.     Gold Nanoparticles Coated with Gadolinium Chelates as Multifunctional Contrast Agents

HeeKyung Kim1, JiAe Park1, JooHyun Kim1, TaeJung Kim2, YongMin Chang1,3

1Department of Medical & Biological Engineering, Kyungpook national University, Daegu, Sankyuk-dong/Buk-gu, Korea; 2Department of Applied Chemistry, Kyungpook national University, Daegu, Sankyuk-dong/Buk-gu, Korea; 3Department of Diagnostic Radiology and Molecular Medicine, Kyungpook National University , Daegu, Samdeok-dong 2-ga/Jung-gu, Korea

The work is directed toward the synthesis of gold nanoparticles (Au NPs) coated with paramagnetic Gd complex of DTPA-bis(amide) conjugate of cysteine (GdL) for use as a highly efficient MRI contrast agent. Well-dispersed spherical Au NPs coated with gadolinium complexes, abbreviated as Au@GdL, have been obtained; the mean size of Au@GdL is 12-15 nm, and the numbers of GdL are 2.9×103 per Au NP. Au@GdL exhibits high longitudinal (R1) and transverse (R2) relaxivities of 17.9±1.1 mM-1s-1 and 28.2±1.0 mM-1s-1, respectively. This is the demonstration of possible application of Gd-coated Au NPs as a bimodal contrast agent for clinical uses.

 


 
Molecules & Cells:  Novel Imaging Methods
Exhibit Hall 2-3                    Monday 14:00-16:00          Computer 3 

14:00         3146.     Towards the Development of a Single PARACEST MRI Contrast Agent for Tumor PH Measurements

Vipul Ravindra Sheth1,2, Guanshu Liu3, Yuguo Li1, Mark D. Pagel1

1Biomedical Engineering, University of Arizona, Tucson, AZ, USA; 2Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA; 3Radiology, Johns Hopkins University, Baltimore, MD, USA

We have developed a single MRI contrast, Yb-DO3AoAA, which generate two PARAmagnetic Chemical Exchange Saturation Transfer (PARACEST) effects from an amide and amine on the agent. Because the exchange rate of protons between these two group and water have different dependencies on pH, we have shown that the ratio of these PARACEST effects is correlated with pH independent of concentration of the agent. By applying an acid-base catalyzed exchange model to the analysis of the exchange rates of these groups we have established the link between the PARACEST effects of the agent and the pH measurement.

14:30         3147.     Mapping Tissue Oxygen Tension Using 1H MR Based Nanoemulsion

Praveen Gulaka1, Tina Darjazanie2, Ralph P. Mason2, Vikram D. Kodibagkar2

1Biomedical Engineering, UT Southwestern Medical Center at Dallas, Dallas, TX, USA; 2Radiology, UT Southwestern Medical Center at Dallas, Dallas, TX, USA

The ability to quantitatively measure tissue oxygen tension (pO2) non-invasively may have a significant impact on understanding mechanisms of tissue function and in clinical prognosis of disease. The linear dependence of R1 of fluorocarbon 19F NMR resonances on pO2 has been studied extensively. Hexamethyldisiloxane (HMDSO) has been previously identified as an analogous 1H based pO2 reporter molecule by in vivo spectroscopy and imaging (PISTOL technique). We now present data demonstrating the calibration of HMDSO based nanoemulsions and mapping tissue oxygenation in response to oxygen challenge following intra tissue injection of these emulsions.

15:00         3148.     A Linear Phase Volume Excitation Coil

Donghyun Kim1,2, J. Rock Hadley1, Glen Morrell1,3

1Utah Center for Advanced Imaging Research, University of Utah, Salt Lake City, UT, USA; 2Physics Department, University of Utah, Salt Lake City, UT, USA; 3Department of Radiology, University of Utah, Salt Lake City, UT, USA

An RF excitation coil with uniform transverse magnetic field amplitude but linearly varying phase has been shown to be optimal for fidelity of excitation with parallel transmission, and is also useful for reduced SAR excitation and for gradient-less imaging (TRASE). Such field profiles have been previously obtained with twisted birdcage coil designs. We present simulation results for a new coil design based on non-resonant microstrips which achieves excellent homogeneity of the transverse magnetic field with linear phase variation along the long axis of the coil.

15:30         3149.     Dynamic MRI Assays of Endothelial Permeability for the Non-Invasive Differentiation of Tumors with High from Tumors with Low VEGF-Activity

Clemens C. Cyran1, Barbara Sennino2, Yanjun Fu3, Victor Rogut3, Bundit Chaopathomkul3, David M. Shames3, Michael F. Wendland3, Donald M. McDonald2, Robert C. Brasch3

1Department of Clinical Radiology, University Hospitals Munich - Grosshadern, Munich, Germany; 2Comprehensive Cancer Center, Cardiovascular Research Institute, and Department of Anatomy, University of California San Francisco, San Francisco, CA, USA; 3Radiology, University of California San Francisco, San Francisco, CA, USA

Dynamic MRI assays of endothelial permeability were evaluated for their potential to differentiate tumors with high intrinsic vascular endothelial growth factor (VEGF) activity from tumors with low VEGF-activity by correlating dynamic MRI assays of endothelial permeability with immunohistochemical measurements of VEGF on a tumor-by-tumor basis. Subcutaneous breast cancer xenografts with different levels of intrinsic VEGF-activity were grown in rats and imaged by MRI using the macromolecular contrast agent albumin-(Gd-DTPA) 27. Non-invasive MRI results correlated significantly with invasive immunohistochemical results. Dynamic MRI assays of endothelial permeability could be clinically applicable to define the suitability of patients for VEGF-inhibiting anti-angiogenic drug therapy.

 
Exhibit Hall 2-3                    Tuesday 13:30-15:30          Computer 3

13:30         3150.     Equilibrium Transcytolemmal Water Exchange Kinetics Depend on Yeast Cell ATP Level: Potentially High Spatiotemporal Resolution in Vivo MR Access to Cellular Energetics

Yajie Zhang1, Marie Poirier-Quinot2, Charles S. Springer3, James A. Balschi1

1NMR Laboratory for Physiological Chemistry, Brigham and Women's Hospital, Boston, MA, USA; 2Unite de Recherche en Resonance Magnetique Medicale, University of Paris Sud, Orsay, France; 3Advanced Imaging Research Center, Oregon Health Science University, Portland, OR, USA

The extracellular relaxation agent, GdDTPA2- was used to distinguish intra- and extracellular 1H2O signals by altering their T1 values. Equilibrium transcytolemmal water exchange kinetics were quantified using two-site-exchange analysis to obtain the mean intracellular water life time (ôi). The hypothesis that ôi correlates with cellular energetics was tested in yeast cells. ôi was inversely linearly correlated with cellular ATP content. Thus, ôi acts as a sensitive biomarker for the cellular energetics. ôi can be determined from pharmacokinetic analyses of in vivo 1H2O DCE-MRI studies. This could allow much higher resolution cellular energetics mapping than with in vivo 31P MRI.

14:00         3151.     Ferromagnetic Hybrid Nanoparticles for Guided Magnetic Hyperthermia

Vít Herynek1,2, Emil Pollert3, Pavla Jendelová2,4, Ondøej Kaman3,5, Miroslav Veverka3, Pavel Veverka3, Eva Syková2,4, Milan Hájek2,6

1Department of Radiodiagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; 2Center for Cell Therapy and Tissue Repair, Second Medical Faculty, Charles University, Prague, Czech Republic; 3Institute of Physics, ASCR, Prague, Czech Republic; 4Institute of Experimental Medicine, ASCR, Prague, Czech Republic; 5Faculty of Science, Charles University, Prague, Czech Republic; 6Department of Radiodiagnostic and Interventional Radiology,, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

We have synthesized, physically characterized and tested coated ferromagnetic manganese perovskite particles. SiO2 coating minimizes toxicity in cell cultures and the particles can be used as cellular labels for guided termoablation. Ferromagnetic particles can be heated by external high frequency electromagnetic field. Thermoablation is self-controlled due to low Curie temperature, the material cannot be heated to temperature over Tc.

14:30         3152.     Quantitative Molecular Imaging with a Dual Modality MR and Fluorescence Diffuse Optical Imaging System: Phantom Study

Yuting Lin1, Han Yan1, Orhan Nalcioglu1, Gultekin Gulsen1

1Center for functional onco imaging, University of California, Irvine, CA, USA

Quantitative molecular imaging is essential in many applications. An ideal molecular imaging technique should have both high sensitivity for molecular probes and also provide high-resolution images. Our solution to this demanding requirement is to employ a multimodality imaging strategy. In this study, a CCD based non contact fluorescence tomography system was built. We constructed multi-modality phantoms with MRI contrast agent, Gd-DTPA, and optical contrast agent, ICG. Our result shows that the true fluorophore concentration can only be recovered when both modalities are employed. In the future, this combined system has a great potential for quantitative molecular imaging.

15:00         3153.     Direct Imaging of Ferumoxides Using Magnetic Particle Imaging: Sensitivity, and Instrument Construction

Patrick Goodwill1, Gary Lee1, Greig Scott2, Pascal Stang2, Steve Conolly3

1Joint Graduate Group in Bioengineering, UC Berkeley / UCSF, Berkeley, CA, USA; 2Electrical Engineering, Stanford University, Stanford, CA, USA; 3Bioengineering, UC Berkeley, Berkeley, CA, USA

Magnetic Particle Imaging (MPI) is a new imaging modality that promises long-term detection and tracking of nano-mol/L concentrations of super-paramagnetic iron oxide (SPIO) commonly used as MRI contrast agents. We measured the sensitivity of a small bore (3.8cm free bore, 1.5cm usable bore) prototype MPI system. The prototype we have developed uses narrowband MPI, allowing small receive bandwidths at high frequencies with a clear path towards body noise dominance. With the significant SNR improvement over MRI, we see great potential for MPI to directly detect SPIOs enabling rapid angiography, inflammation tracking and stem cell tracking.

 
Exhibit Hall 2-3                    Wednesday 13:30-15:30          Computer 3

13:30         3154.     Improved Sensitivity in 19F Cellular Imaging Using Nonconvex Compressed Sensing

Andre Fischer1,2, Thomas Christian Basse-Lüsebrink2,3, Thomas Kampf2,4, Gesa Ladewig3, Martin Blaimer1, Felix Breuer1, Guido Stoll3, Wolfgang Rudolf Bauer4, Peter Jakob1,2

1Research Center Magnetic Resonance Bavaria e.V., Würzburg, Germany; 2Department for Experimental Physics 5, University of Würzburg, Würzburg, Germany; 3Neurology, University of Würzburg, Würzburg, Germany; 4Medical Clinic and Polyclinic I, University of Würzburg, Würzburg, Germany

19F imaging suffers from low signal intensities and long data acquisition times due to averaging. Since the distribution of the 19F signal is sparse in the image domain, we propose a Compressed Sensing (CS) reconstruction schema. CS allows the reconstruction of sparse undersampled datasets. Classical Chemical Shift Imaging (CSI) is a purely phase encoded technique; therefore, random sampling can be applied which is optimal for the CS reconstruction due to the incoherent undersampling artifacts. In this work we demonstrate the potential of Nonconvex CS [4] in cellular imaging using 19F CSI. This study is the first one where CS exploits solely the sparsity in image space and not in the spectral dimension. Initial results from retrospectively undersampled phantom and in-vivo experiments are presented. These experiments demonstrate that it is possible to obtain almost the same information content by collecting only a significantly reduced fraction of all phase encoding steps in 19F CSI.

14:00         3155.     Diffusion Enhanced Sensitivity of BSSFP Quantification of Micron-Sized Superparamgnetic Iron Oxide

Ahmed Magdy Elkady1,2, Chris Van Bowen1,2

1Biomedical Engineering, Dalhousie University, Halifax, NS, Canada; 2National Research Council of Canada, Institute for Biodiagnostics (Atlantic), Halifax, NS, Canada

The current work presents the first report of the use of balanced steady state free precession (bSSFP) for quantitative imaging of micron-sized superparamagnetic iron oxide particles (MPIO). Segmented inversion recovery (IR) bSSFP and variable echo time (VT) bSSFP are shown to be 2-3 times more sensitive than conventional spin echo (SE) quantitative imaging of MPIO. The enhanced MPIO quantification sensitivity of bSSFP compared to SE is demonstrated to be due to diffusion effects caused by field micro-gradients created by MPIO.

14:30         3156.     Theoretical Considerations on the Quantification of Iron Oxide Labeled Cells in Vivo

Thomas Kampf1, Christian Herbert Ziener1, Peter Michael Jakob1, Wolfgang Rudolf Bauer2

1Experimental Physics 5, University of Wuerzburg, Wuerzburg, Germany; 2Medizinische Klinik und Poliklinik I, University of Wuerzburg, Wuerzburg, Germany

Iron oxide contrast-enhanced MRI has become a commonly used tool in molecular and cellular imaging. Cell labeling with iron oxide nanoparticles leads to signal attenuations in T2 and T2* weighted MR images on the site of the cell. Until now the problem of quantifying these labeled cells in vivo is not completely solved. The major problem is the unknown uptake of the iron oxide by the cells in vivo. This work investigates a possible solution by evaluating the transverse relaxation times and their diffusion dependence theoretically on the typical parameter range of in vivo situations.

15:00         3157.     Differentiation of Intracellular and Extracellular SPIO Nanoparticles with R2 and R2* Mapping

Wei Liu1,2, Julien Senegas3, Melissa Smith2, Joseph A. Frank2

1Clinical Sites Research Program, Philips Research North America, Briarcliff Manor, NY, USA; 2Clinical Center, National Institutes of Health, Bethesda, MD, USA; 3Phlips Research Europe, Hamburg, Germany

The quantitation of SPIO labeled cells by MRI is often confounded by the need to account for the possible existence of extracellular SPIOs that are present as a result of cell labeling with incomplete washing of cells or cell death following direct injection of labeled cells into tissues. This study investigated quantitative approaches for differentiation of intracellular and extracellular SPIOs using both R2 and R2* mapping. Experiment with phantoms containing mixtures of free SPIOs and SPIO labeled cells demonstrated a very good linear correlation between the estimated ratios of intracellular and extracellular SPIOs and the theoretical values.

 
Exhibit Hall 2-3                    Thursday 13:30-15:30          Computer 3

13:30         3158.     Contrast Quantification of MPIO Labeled Cell Migration in the OB of Mice as a Read Out for the Efficiency of in Situ Labeling Strategies

Ruth Vreys1, Marleen Verhoye1,2, Annemie Van der Linden1

1Bio-Imaging Lab, University of Antwerp, Antwerp, Belgium; 2Vision Lab, University of Antwerp, Antwerp, Belgium

We describe a method for contrast quantification based on threshold segmentation of hypointense voxels. The method uses four VOIs to be able to correct for signal bias between the OB ipsilateral and OB contralateral to the injection and to correct for false positive hypointense voxels originating from other sources than MPIOs. The results revealed contrast accumulation for two out of four strategies to label eNPC in mice by intraventricular MPIO injections. This method could be useful for quantification of neurogenesis capacity.

14:00         3159.     Characterization of MR Contrast Enhancement in Murine Advanced Atherosclerotic Plaque After Administration of 24p3 (NGAL)-Targeted Micelles.

Bernard C. te Boekhorst1, Sandra M. Bovens1, Krista den Ouden1, Marcel G. Nederhoff1, Kees W. van de Kolk1, Maarten J. Cramer1, Michiel ten Hove1, Pieter Doevendans1, Robert E. Poelmann2, Gerard Pasterkamp1, Cornelis J. van Echteld1

1Dept. of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands; 2Anatomy and Embryology, Leiden Universitair Medisch Centrum, Leiden, Netherlands

Human neutrophil gelatinase associated lipocalin (NGAL) has been shown to be upregulated in carotid atherosclerotic plaques and stabilizes matrix metalloproteinases, which are an important hallmark of advanced atherosclerosis. MRI of atherosclerotic vessels before and after administration of gadolinium-containing NGAL-targeted contrast agents could help distinguish stable from unstable plaque phenotypes. We report the characterization of plaque dynamics of 24p3 (mouse homologue of NGAL)-targeted micelles. 24p3-targeted micelles led to the highest normalized enhancement ratio (NER) (2.65) at 72 hours after administration, while the non-conjugated and isotype-conjugated micelles showed the highest NER at 24 hours after administration (respectively 2.22 and 1.37).

14:30         3160.     Low Threshold Detection of USPIO Concentrations in Different Environments Simulating Tissue Diversity

Sherif R. Fahmy1, Todd Parrish1

1Northwestern University, Chicago, IL, USA

Different diffusion environments are simulated using solutions of varying PEG 400 volume fraction. A double-band pulse is used for off-resonance pre-saturation, and pulse parameters are tuned to obtain the best detection of USPIO agent. The threshold of lowest detectable concentration of USPIO in the different diffusion environments is noted. The significance of the work is that it verifies the ability of the off-resonance saturation technique to detect low concentrations of USPIO in environments that simulate real biological or clinical applications.

15:00         3161.     Separation of SPIO and Air Bubbles for Molecular Imaging

Tian Liu1,2, Richard Wong1,2, Pascal Spincemaille2, Yi Wang1,2

1Biomedical Engineering, Cornell University, Ithaca, NY, USA; 2Radiology, Weill Cornell Medical College, New York, NY, USA

Dark T2* contrast of SPIO has been widely used in cell tracking in molecular MRI, but this negative contrast may be indistinguishable from the one generated by air bubbles that are commonly observed in gel phantoms due to their porous nature. In this study, we propose to distinguish air bubble from SPIO labeled cells by quantifying the magnetization at two different field strengths, 1.5T and 3T, using the fact that SPIO magnetization is typically saturated at field > 1T while the magnetization of air increases linearly with field strength.

 


 
Molecules & Cells:  Novel Applications
Exhibit Hall 2-3                    Monday 14:00-16:00          Computer 4

14:00         3162.     Endosomal Escape of Gd-Agents Activated by External Photochemical Stimulus

Eliana Gianolio1, Francesca Arena1, Anders Hogset2, Silvio Aime1

1Chemistry IFM, University of Torino, Torino, Italy; 2PCI Biotech AS, Oslo, Norway

The novel Photochemical internalisation (PCI) technology, that promotes the release of endocytosed molecules into cells cytosol, has been succesfully adapted to MRI applications in order to improve the efficiency of Gd-containing probes internalized by cells through pinocytotic mechanism. The release of endocytosed paramagnetic probes into the cytosol removes the relaxivity quenching produced by the entrapment of high concentrations of Gd-complexes into endosomes thus traducing in a great enhancement in signal intensity if compared with the case of endosomes compartimentalized agents.

14:30         3163.     Harnessing Competing Endocytic Pathways for Overcoming the Tumor-Blood Barrier: MRI and NIR Imaging of Bifunctional Contrast Media

Helena Migalovich-Sheikhet1, Vyacheslav Kalchenko2, Nava Nevo2, Fortune Kohen1, Michal Neeman1

1Biological Regulation, Weizmann Institute of Science, Rehovot, Israel; 2Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel

The uptake of targeted bifunctional daidzein-BSA MRI/NIR contrast media to human ovarian carcinoma cells was achieved by two competing endocytic pathways. One is BSA mediated-caveolae dependent and could be modulated by nystatin or BSA saturation, and the second is daidzein mediated and caveolae independent. The ability to manipulate caveolae-mediated sequestration of albumin by perivascular tumor myofibroblasts allowed to effectively overcome the tumor-blood barrier, increasing delivery of daidzein-BSA-GdDTPA/CyTE777 to the tumor cells. In view of the cardinal role of albumin in affecting the bioavailability of drugs, this approach could potentially facilitate the delivery of therapeutics and contrast media to the tumor.

15:00         3164.     Electroporation Facilitated Intracellular Delivery of Contrast Agent to Probe Sub-Cellular Metabolite Compartmentalization in Vivo

David Alberg Holm1,2, Ian John Rowland3

1Danish Research Centre for Magnetic Resonance, Hvidovre Hospital, Hvidovre, Denmark; 2Informatics and Mathematical Modeling, Technical University of Denmark, Lyngby, Denmark; 3Department of Radiology, University of Wisconsin, Madison, WI, USA

Using electroporation, contrast agents have been delivered into the cytoplasm of rat muscle cells in vivo in order to probe the sub-cellular compartmentalization of MR visible metabolites. Following electroporation, both Magnevist and Gadovist provided water relaxation enhancement in hind limb muscle for periods up to 2 months. During this time, creatine and choline relaxation times were significantly reduced suggesting that a significant component of the metabolites also reside within the cytoplasm.

15:30         3165.     Micro-MR Angiography Using Gd-Loaded Micelles as Intravascular Contrast Agents in Mouse Models Amyloid Angiopathy

Lindsay K. Hill1, Karen C. Briley-Saebo2, Moustafa Douadi1, Asad Baig1, Susan Pun1, Brian J. Nieman3, Daniel H. Turnbull1,3, Zahi A. Fayad2, Thomas Wisniewski4, Youssef Z. Wadghiri1

1Radiology, NYU School of Medicine, New York, NY, USA; 2Radiology, Mount Sinai School of Medicine, New York, NY, USA; 3Skirball Institute of Biomolecular Medicine, NYU School of Medicine, New York, NY, USA; 4Pathology&Neurology&Psychiatry, NYU School of Medicine, New York, NY, USA

Susceptibility-based MRI probes targeting Amyloid β deposits in vessels wall can be difficult to distinguish from normal and abnormal physiological events leading to dark enhancement. In this study, we proposeSlinium-loaded micelles as long living intravascular agents to achieve in vivo 3D micro-angiograms in mice. The steady state positive enhancement obtained from the construct and restricted to the vascular network is maintained long enough to achieve highly resolved vascular data sets with 150-um and 100-um isotropic spatial resolution within 30-minutes and 100-minutes acquisition time, respectively.

 
Exhibit Hall 2-3                    Tuesday 13:30-15:30          Computer 4

13:30         3166.     Nanoparticle Detection of Vascular Inflammation in Mouse Carotid Artery at 7T

Hisanori Kosuge1, Masahiro Terashima1, Masaki Uchida2, Sarah Sherlock3, Philip S. Tsao1, Mark J. Young2, Trevor Douglas2, Hongjie Dai3, Michael V. McConnell1

1Cardiovascular Medicine, Stanford University, Stanford, CA, USA; 2Chemistry and Biochemistry, Montana State University, Bozeman, MT, USA; 3Chemistry, Stanford University, Stanford, CA, USA

Inflammation plays a critical role in the progression of atherosclerosis. Magnetite incorporated human ferritin protein cages and graphite/FeCo core-shell nanocrystals may allow noninvasive high-field MRI detection of vascular macrophages in mouse arteries. We demonstrate that MRI at 7T can detect vascular macrophages with magnetite protein cage nanoparticles and graphite/FeCo core-shell nanocrystals in mouse atherosclerotic lesions.

14:00         3167.     Quantitative Molecular Imaging of Thrombi with Fibrin-Targeted PARACEST Perfluorocarbon Nanoparticles

Kejia Cai1, Garry Kiefer2, Shelton Caruthers1,3, Samuel Wickline1, Gregory Lanza1, Patrick Winter1,4

1Washington University, St. Louis, MO, USA; 2Macrocyclics, Dallas, TX, USA; 3Philips Healthcare, Andover, MA, USA; 4Kereos, Inc., St. Louis, MO, USA

Molecular imaging of fibrin could help detect ruptured plaques, the cause of heart attacks and strokes. Fibrin-targeted PARACEST (PARAmagnetic Chemical Exchange Saturation Transfer) nanoparticles were formulated to demonstrate molecular imaging of clots with dual PARACEST and 19F MRI at 11.7T. PARACEST nanoparticles in suspension had a much shorter bound water lifetime than the parent water soluble chelate, leading to lower contrast. When targeted to clots, however, PARACEST nanoparticles showed an improved detection limit of 2.3 nM, possibly due to a reduction in the bound water lifetime, making the PARACEST exchange kinetics more optimal.

14:30         3168.     MRI Detection of Progenitor Cell Migrations During Postnatal Rat Brain Development by in Situ MPIO Labeling

Jian Yang1,2, Jianxin Liu3, Gang Niu1, Rong Wang1, Yong Liu4, BoLang Yu1, Ed Xuekui Wu2

1Medical Imaging Center of The First Hospital, The School of Medicine,Xi'an Jiaotong University, Xi'an, China; 2Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, China; 3Institute of neurobiology, The School of Medicine, Xi'an Jiaotong University, Xi'an, China; 4Institute of neurobiology, The School of Medicine, Xi'an Jiaotong University,, Xi'an, China

In this study, micron-sized iron oxide particles (MPIOs) were injected into the left anterior lateral ventricle of 10-day-old normal rats. T2- and T2*-weighted images were acquired using a 7T scanner at day 1, 3, 7 and 14 after the MPIO injection. Histological analyses were then performed to identify MPIOs in different migrating cells, namely, neural progenitor and astrocytes-like progenitor cells. The migrating pathways of the MPIO-labeled endogenous progenitors exhibited a predominantly bidirectional, rostrocaudal pattern in tangential orientation. Such in situ MPIO labeling approach opens the possibility of using MRI to study the mechanism of cell migration in developing brain.

15:00         3169.     Identification of Advanced Atherosclerotic Plaque in Abdominal Aorta in a Murine Atherosclerotic Model with 24p3 (Mouse Homologue of Neutrophil Gelatinase-Associated Lipocalin)-Targeted Micelles and MRI.

Bernard C. te Boekhorst1, Sandra M. Bovens1,2, Krista den Ouden1, Marcel G. Nederhoff1,2, Kees W. van de Kolk1, Maarten J. Cramer1, Michiel ten Hove1, Pieter Doevendans1, Robert E. Poelmann3, Gerard Pasterkamp1, Cornelis J. van Echteld1

1Dept. of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands; 2InterUniversity Cardiology Institute of the Netherlands, Utrecht, Netherlands; 3Anatomy and Embryology, Leiden Universitair Medisch Centrum, Leiden, Netherlands

Neutrophil gelatinase-associated lipocalin (NGAL) in human carotid artery plaque has been reported to correlate with the occurrence of acute cerebrovascular events. We calculated the normalized enhancement ratio (NER) of enhanced regions on T1 weighted MR images 72 hours after administration of both 24p3 (mouse homologue of NGAL) targeted and isotype-conjugated micelles (labeled with fluorophore and gadolinium). Maximal NER was respectively 2.25 and null. Fluorescence microscopy (FM) showed colocalization of abundantly present 24p3-targeted micelles and especially 24p3, and, only to a minor extent, macrophages. Isotype-conjugated micelles were only to a minor extent present in the plaque and colocalized only with macrophages.

 
Exhibit Hall 2-3                    Wednesday 13:30-15:30          Computer 4

13:30         3170.     Molecular Imaging Using Targeted Nanoparticles for Non-Invasive Detection of Renal Inflammation

Natalie J. Serkova1, Brian A. Larsen2, Brandon Renner3, Kendra M. Hasebroock1, Erica L. Bradshaw-Pierce1, Michael Holers3, Conrad Stoldt4, Joshua M. Thurman3

1Anesthesiology, University of Colorado Health Sci, Aurora, CO, USA; 2Mechanical Engineering, University of Colorado Boulder, Boulder, CO, USA; 3Medicine, University of Colorado Health Sci, Aurora, CO, USA; 4Mechanical Engineering, University of Colorado Boulder, Aurora, CO, USA

CR2 (CD21) is a transmembrane protein expressed on immunocompetent cells, which binds the cleavage fragments of C3. In the MRL/lpr model of lupus nephritis, injection with the CR2-conjugated SPIO caused a significant reduction in T2-relaxation times in nephritic kidneys; healthy control mice had no changes in T2 values. Furthermore, the injection of untargeted SPIO particles did not affect the T2-values of the kidneys in MRL/lpr mice. Thus, by conjugating the SPIO nanoparticles with recombinant CR2 protein we have developed a contrast agent that specifically targets the site of complement activation. This method can non-invasively detect active inflammation in immune-complex glomerulonephritis.

14:00         3171.     Detection of Macrophage Accumulation After Heart Transplantation in a Rat Using a Novel Nano-Sized Iron Oxide Particle with High Relaxivity

Haosen Zhang1, Chih-Lung Chen2, Qing Ye1, Kevin Hitchens1, Wen-Yuan Hsieh2, Hsiu-Hua Huang2, Yi-Shan Lin2, HsinHsin Shen2, Mu-Jen Young2, Wei-Lin Yu2, Ying-Ting Huang2, Lesley Foley1, Yijen Wu1, Jassy Wang2, Chien Ho1

1Pittsburgh NMR Center for Biomedical Research, Department of Biological Science , Carnegie Mellon University, Pittsburgh, PA, USA; 2Industrial Technology Research Institute, Taiwan

The aim of this study was to detect the macrophage accumulation by in vivo MRI in a rat heterotopic heart transplantation model of acute rejection using a biodegradable, nano-sized iron oxide particle with high relaxivity. After being labeled ex vivo with ITRI-IOP, punctuate spots of hypointensity were observed on the mid-wall of the transplant heart 24 hrs post injection. Ex vivo imaging of the fixed heart demonstrated abundance of punctuated spots of hypointensity that might be caused by the iron-loaded macrophages. Histological analysis and iron staining confirmed the presence of iron and macrophages in the corresponding tissue section as MRI.

14:30         3172.     1H/19F Molecular MR-Imaging in Mouse Models of Acute and Chronic Inflammation

Gert Klug1, Thomas Basse-Lüsebrink2, Christian Schnell1, Thomas Kampf2, Elisabeth Bauer1, Volker Herold2, Marco Parczyk2, Eberhard Rommel2, Guido Stoll3, Peter Michael Jakob2, Wolfgang Rudolf Bauer1

1Medizinische Klinik und Poliklinik I, Universitätsklinikum Würzburg, Würzburg, Germany; 2Experimentelle Physik 5, Universität Würzburg, Würzburg, Germany; 3Abteilung für Neurologie, Universitätsklinikum Würzburg, Würzburg, Germany

This study evaluates the capability of 19F-containing liposomes (VS1000H) for imaging and quantifying inflammatory processes. As a model for non-ischemic, sterile inflammation mice were investigated after subcutaneous TNF-alpha injection. Furthermore the uptake into activated atherosclerotic plaque macrophages of apoE-/- mice is investigated. We observed a significant uptake of VS1000H into models of inflammation. By excluding excessive tissue damage and bleeding as confounding factor this data suggests molecular MRI using liposomes containing 19F is a valuable tool for the detection of inflammatory processes. The results in apoE-/- mice indicate an uptake of VS1000H by atherosclerotic plaque macrophages.

15:00         3173.     Gd-Containing Dendrimer as a Novel T1-Weighted Lung MRI Contrast Agent

Wen-Yuan Hsieh1, Dhakshanamurthy Thirumalai2, Chien-Yuan Lin3, Sui-Shan Lin3, chen Chang3, Shin-Shin Shen4, Jassy Wang2

1Material and Chemical Research Laboratories, Industrial Technology Research Institute , Hsinchu, taiwan, Taiwan; 2Material and Chemical Research Laboratories, HsinJu, Taiwan; 3Academia Sinica, Taipei, Taiwan; 4Biomedical Lab, HsinJu, Taiwan

Synthesis of a novel and hitherto unknown ¡§starburst¡¨ Gd-containing dendritic contrast agent from pentamethylcyclopentasiloxane and polyethylene glycol (PEG) and its contrast enhancement on the lung tissue of mice during MR imaging were described. This study present great enhancement of lung imaging using MRI with novel T1 contrast agent.

 
Exhibit Hall 2-3                    Thursday 13:30-15:30          Computer 4

13:30         3174.     Macromolecular Versus Small Molecular MRI Contrast Media for Monitoring Anti-Angiogenic Drug Effect of Bevacizumab on Experimental Human Breast Cancer Xenografts

Clemens C. Cyran1,2, Yanjun Fu2, Victor Rogut2, Bundit Chaopathomkul2, David M. Shames2, Michael F. Wendland2, Robert C. Brasch2

1Department of Clinical Radiology, University Hospitals Munich - Grosshadern, Munich, Germany; 2Radiology, University of California San Francisco, San Francisco, CA, USA

The macromolecular contrast media (MMCM) albumin-(Gd-DTPA) 27 was compared to the small molecular contrast media (SMCM) Gd-DTPA for their suitability to monitor early anti-angiogenic effect of bevacizumab on human breast cancer xenografts in dynamic MRI assays of endothelial permeability in a tandem experiment. Rats were imaged at baseline and 24h after intraperitoneal bevacizumab application. MRI assays of tumor endothelial permeability revealed a significant decrease of endothelial permeability using albumin-(Gd-DTPA) 27 whereas no significant effect was detected using Gd-DTPA. The MMCM albumin-(Gd-DTPA) 27 proved to be superior to the SMCM Gd-DTPA for the detection of early anti-angiogenic effect of bevacizumab.

14:00         3175.     Intra-Individual In-Vivo Comparison of Gd-Contrast Agents for Quantitative Pharmacokinetic Analysis Using Dynamic Contrast Enhanced MR Imaging

Jiachao Liang1, Steffen Sammet1, Xiangyu Yang1, Guang Jia1, Yukihisa Takayama2, Michael V. Knopp1

1Department of Radiology, The Ohio State University, Columbus, OH, USA; 2Department of Clinical Radiology, Kyushu University, Fukuoka, Japan

The usefulness of magnetic resonance (MR) imaging contrast agents to improve visualization of brain imaging is firmly established. Gadolinium–based MR contrast agents have been approved by the US FDA for MR imaging procedures. Numerous intraindividual comparative studies within different Gd agents at equivalent dose and equivalent magnetic field strength, from 1.5T to 3T, have been investigated. This study evaluates the signal intensity characteristics of dynamic contrast enhanced MR imaging (DCE-MRI) at ultra-high field (7T) in a preclinical beagle brain study with different contrast agents, different injection rates and different injection dosages.

14:30         3176.     Evaluation of an Iron Oxide Contrast Agent in the Visualization of Aortic Valve Sclerosis - A Preliminary Study

Amanda M. Hamilton1,2, Andre JL Belisle1,2, Brian K. Rutt2,3, Ralph Weissleder4, Derek R. Boughner2,5, Kem A. Rogers1

1Anatomy & Cell Biology, University of Western Ontario, London, Ontario, Canada; 2Imaging, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada; 3Radiology, University of Western Ontario, London, Ontario, Canada; 4Massachusetts General Hospital, Boston, MA, USA; 5Medicine, University of Western Ontario, London, Ontario, Canada

Aortic valve sclerosis (AVS) is a prevalent vascular disease with macrophage invasion as a critical pathological feature. This study tested the efficacy of identifying AVS in cholesterol-fed rabbits using passive targeting of macrophages with iron oxide-enhanced MRI. In vivo and ex vivo imaging exhibited evidence of iron oxide uptake in both control and cholesterol-fed rabbit valves. Histopathological analysis revealed iron staining in myofibroblasts in both control and cholesterol-fed rabbit valves as well as in macrophages in cholesterol-fed rabbits only. Our findings suggest that passive targeting of macrophages is insufficient for early AVS identification and macrophage-targeted contrast agents should be investigated.

15:00         3177.     A Novel Macrophage Imaging Strategy Using Apoptotic Liposomes Incorporating Phosphatidylserine and AZ-Cholesterol

Andrei Maiseyeu1, Sashwati Roy2, Georgeta Mihai1, Nisharahmed Kherada1, Orlando P. Simonetti1, Chandan K. Sen2, Sampath Parthasarathy2, Sanjay Rajagopalan1

1Davis Heart & Lung Research Institute, The Ohio State University, Columbus, OH, USA; 2Department of Surgery, The Ohio State University, Columbus, OH, USA

Phosphatidylserine (PS) residues of cell membranes and oxidized lipids are apoptotic cues to engage macrophage engulfment. In order to express these cues on a liposomal surface to provide a target for macrophage engulfment, we synthesized a novel cholesterol derivative that in combination with PS- and Gd-lipids forms an efficient contrast agent (Az-Chl). In vivo MR performance of Az-Chl was evaluated on WHHL rabbit model using 1.5T Siemens clinical scanner while pharmacokinetics were estimated by mass spectrometry. Az-Chl liposomes to mimic apoptotic particles allow for in-vivo imaging of macrophages in atherosclerosis. Our findings have important implications for identification of unstable plaque

 


 
Advanced Spine Imaging
Exhibit Hall 2-3                    Monday 14:00-16:00          Computer 5

14:00         3178.     Distortion Correction in Spinal Cord DTI: What’s the Best Approach?

Julien Cohen-Adad1,2, Henrik Lundell3,4, Serge Rossignol2

1INSERM, Univ Paris 6, Pitie Salpetriere Hospital, Paris, France; 2GRSNC, Physiology department, Univ Montreal, Montreal, QC, Canada; 3Danish Research Center for MR, Copenhagen University Hospital, Hvidovre, Denmark; 4Inst. Neurosci & Pharmacol, Univ Copenhagen, Copenhagen N, Denmark

Susceptibility artifacts induced by B0-field inhomogeneities are particularly problematic in spinal cord EPI, inducing large geometric and intensity distortions. There exists a variety of approaches to correct for distortions a posteriori. In this study, we compare some of them, including the phase field map, the reversed gradient, the point spread function (PSF) and the co-registration methods. We show that the reverse gradient and PSF approaches yield best results towards large (lower cervical cord) and small (inter-vertebral disks) distortion patterns. This study also investigates the impact of distortion correction on diffusion tensor imaging of the human spinal cord.

14:30         3179.     Parallel RF Transmission for Clinical MR Imaging of the Human Spinal Cord at 3.0 Tesla: Preliminary Results

Michael Nelles1, Roy König1, Jürgen Gieseke1,2, Marjolijn Guerand-van Battum2, Marco Nijenhuis2, Guido Kukuk1, Daniel Thomas1, Magnus Andersson1, Beate Koberstein1, Hans Heinz Schild1, Winfried A. Willinek1

1Dept. of Radiology / Neuroradiology, University of Bonn Hospital and Medical School, Bonn, NRW, Germany; 2Philips Healthcare, Best, Netherlands

Parallel RF transmission holds the promise of reducing dielectric resonance effects at high field strengths and enables control of RF distribution to optimize RF deposition. Up to now, parallel RF transmission has not been used or fully tested on routine clinical high-field MR systems. Our study demonstrates that parallel RF transmission in MR imaging of the spinal cord yields a diagnostic image quality readily comparable to that of standard single transmission sequences, while at the same time saving a significant amount of examination time.

15:00         3180.     Clinical Evaluation of Reduced Field-Of-View Diffusion Imaging of the Human Spinal Cord

Greg Zaharchuk1, Emine Ulku Saritas2, Ajit Shankaranarayan3, Dwight Nishimura2, Nancy Jane Fischbein1

1Department of Radiology, Stanford University, Stanford, CA, USA; 2Department of Electrical Engineering, Stanford University, Stanford, CA, USA; 3Appled Sciences Laboratory - West, GE Healthcare, Menlo Park, CA, USA

The combination of higher spatial resolution and decreased imaging artifacts associated with reduced FOV spinal cord DWI improves clinical evaluation of both normal and pathological conditions. We will review the basics of the technique and present multiple cases in which rFOV DWI was helpful for clinical diagnosis.

15:30         3181.     Slice-By-Slice Motion Correction in Spinal Cord FMRI: SliceCorr

Julien Cohen-Adad1,2, Serge Rossignol3, Richard D. Hoge4

1INSERM, Univ Paris 6, Pitie Salpetriere Hospital, Paris, France; 2GRSNC, Physiology department, Univ Montreal, Montreal, QC, Canada; 3GRSNC, Physiology department , Univ Montreal, Montreal, QC, Canada; 4UNF, Univ Montreal, Montreal, QC, Canada

To date, spinal cord BOLD-fMRI has generated considerable efforts to obtain robust activation maps. One possible cause of the low sensitivity of this technique in the spinal cord are the relatively narrow activation blobs, making activation maps extremely sensitive to subject motion. This study demonstrates the benefits of 2D versus 3D methods to correct subject motion in axial fMRI time series of the spinal cord. SliceCorr, a spinal cord-dedicated method has been developed and compared with 3D-based methods, using human dataset of the whole cervical spinal cord. Results showed the least residual motion for the SliceCorr-corrected datasets in all subjects.

 
Exhibit Hall 2-3                    Tuesday 13:30-15:30          Computer 5

13:30         3182.     Measurement of the Spinal Stenosis at and in the Presence of a Degenerated Cervical C5-C6 Segment as a Function of Head-Neck Posture

Mahmoud Abdulhusain1

1Kuwait University, Jabria, Kuwait

Spinal degenerative changes at the lower cervical levels especially C5-C6 is an increasingly common condition in which the spinal canal and cord tend to be compressed by budging discs. In people suffering from this condition an essential question is how the daily repetitive postures of the head-neck relate to a C5-C6 spinal stenosis. This research reports the Spinal Canal Area (SCA) changes at C5-C6 across an array of head-neck postures in a 40 year old volunteer diagnosed with diffuse disc bulge resulting in moderate cord compression at C5-C6. It shows the head-neck posture to play a part in this condition.

14:00         3183.     3T MR Neurography in Lumbosacral Nerves: An Anatomical Study

Yan Ping CHEN1, Lin Yang2

1Imaging diagnostic center, Southern medical University, Guangzhou, Guangdong, China; 2Radiology, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China

 

 

14:30         3184.     Susceptibility Weighted Imaging of the Spinal Veins

kinya ishizaka1, kohsuke kudoh2, noriyuki fujima1, yuri zaitsu1, satoshi terae1, makoto sasaki2, hiroki shirato1

1Hokkaido University Hospital, Sapporo, Hokkaido, Japan; 2Advanced Medical Research Center, Iwate Medical Univeristy

The purpose of this study is to evaluate visualization of normal spinal veins.Twenty healthy volunteers were scaned, the anterior median vein , posterior median vein , right and left anterior radiculomedullary veins , and right and left posterior radiculomedullary veins and Sulcal vein were identified in 20, 13, 9, 3, 2, 6 and 0 subjects, respectively. SWI of the spine is feasible, and can offer us an useful informations of spinal veins, not only for the anatomical information, but also for the oxygen metabolism.

15:00         3185.     Investigation of Venous Effects in Spinal Cord FMRI Using Hypercapnia

Claudine Gauthier1,2, Julien Cohen-Adad1,3, Jonathan Brooks4, Serge Rossignol1, Richard D. Hoge1,2

1Department of Physiology, Université de Montréal, Montreal, Quebec, Canada; 2Unité de Neuroimagerie Fonctionnelle, Institut universitaire de gériatrie de Montréal, Montreal, Quebec, Canada; 3INSERM U678, Univ Paris 6, Pitié-Salpêtrière Hospital, Paris, France; 4PaIN Group, FMRIB Centre, University of Oxford, UK

Hypercapnia can be used as a control stimulus to study the sensitivity of BOLD responses in the spinal cord as it is is known to cause large increases in perfusion and subsequently in BOLD signal. In this study we built further on previous investigation by comparing responses to hypercapnia and a motor task in the spinal cord and the brain. SWI was also used to investigate the spatial concordance of the most significant responses with large veins.Lar gest activations were found in large veins, both in the brain and the spine, with spatial concordance of hypercapnia and motor task.

 
Exhibit Hall 2-3                    Wednesday 13:30-15:30          Computer 5

13:30         3186.     Assessment of Cervical Spinal Disorders: Comparison of T2-Weighted IDEAL Water-Only Imaging and Fat-Saturated T2-Weighted FSE Imaging

Kimihiko Sato1, Takayuki Masui1, Motoyuki Katayama1, Hiroki Ikuma1, Hidekazu Seo1, Akihiko Kutsuna1, Masayoshi Sugimura2, Kenji Asano3

1Radiology, Seirei Hamamatsu General Hospital, Hamamatsu, Shizuoka, Japan; 2Radiology Center, Seirei Hamamatsu General Hospital, Hamamatsu, Shizuoka, Japan; 3MR Engineering, GE Yokogawa Medical Systems Ltd., Hino, Tokyo, Japan

T2-weighted IDEAL water-only imaging for cervical spinal disorders including posterior neck Lesions

14:00         3187.     Acquisition of 7T Human Spine Imaging

Bing Wu1, Chunsheng Wang1, Roland Krug1, Douglas Kelley2, Yong Pang1, Sharmila Majumder1,3, Xiaoliang Zhang1,3

1Radiology&Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA; 2GE Healthcare, San Francisco, CA, USA; 3UCSF/UC Berkeley Joint Group Program in Bioengineering, SanFrancisco&Berkeley, CA, USA

Ultra-high magnetic field spine image may provide high signal to noise ratio for both human disc imaging and spectroscopy, thus better quantitative assessment of disc health can be achieved. In this work, initial images for human spine were acquired at 7t. Some points for 7T human spine acquisition are discussed.

14:30         3188.     Distribution of MR Signal Intensity Within the Intervertebral Disc: Modifications Occurring with Adolescent Spondylolisthesis and Idiopathic Scoliosis

Delphine Périé1,2, Marjorie Riopel-Methot1,2, Ariane Courville-LeBouyonnec1,2, Daniel Curnier3

1Mechanical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada; 2Research Center, CHU Sainte Justine, Montreal, Quebec, Canada; 3Kinesiology, Université de Montréal, Montreal, Quebec, Canada

A retrospective study had been performed on T2-weighted MR images of twenty nine patients with spondylolisthesis and/or scoliosis. New parameters characterising the distribution of the MR signal intensity within the nucleus zone of the lumbar intervertebral disc were proposed and their quantification revealed modifications attributed to the disease and its level. Future developments will consist in a 3D analysis that will be applied to quantitative MR mapping of relaxation times, magnetization transfer or diffusion parameters within the intervertebral discs of patients suffering from a specific disease.

15:00         3189.     DTI Abnormalities in Sheep Spinal Decompression Sickness: Anisotropy Differences and Histological Comparison

Elizabeth B. Hutchinson1, Ian Rowland2, Aleksey Sobakin3, Neil Kleman4, Dandan Sun4, Peter Ferrazzano5, Marlowe Eldridge5, Mary Elizabeth Meyerand6

1Neuroscience Training Program, University of Wisconsin, Madison, WI, USA; 2Radiology, University of Wisconsin, Madison, WI, USA; 3Veteranary Medicine, University of Wisconsin; 4Neurosurgery, University of Wisconsin, Madison, WI, USA; 5Pediatrics, University of Wisconsin, Madison, WI, USA; 6Medical Physics, University of Wisconsin, Madison, WI, USA

Spinal cord injury due to decompression sickness (DCS) in sheep was investigated using DTI and histology. An injury profile of decreased white matter FA was identified in cases of acute and chronic injury. Histology using FluoroJade, a marker of apoptotic cells, was then performed and there was positive staining in the white matter of acutely injured spinal cord, but not control samples. This study identifies DTI biomarkers of two types of spinal cord damage within spinal DCS and correlates DTI changes with histological information.

 
Exhibit Hall 2-3                    Thursday 13:30-15:30          Computer 5

13:30         3190.     Diffusion Tensor MRI of the Lumbar Spinal Cord in G93A-SOD1 Mice

Clare K. Underwood1, Nyoman Dana Kurniawan2, Tim Dana Butler1, Robyn H. Wallace1

1Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia; 2Centre for Magnetic Resonance, University of Queensland, Brisbane, QLD, Australia

In this paper, we present the use of DTI to measure degeneration in the lumbar spinal cord of the G93A-SOD1 transgenic mouse model of amyotrophic lateral sclerosis (ALS).

14:00         3191.     Preliminary Investigation of Position Dependency of Radial Diffusivity in the Cervical Spinal Cord

Torben Schneider1, Daniel C. Alexander2, Claudia A.M. Wheeler-Kingshott1

1Department of Neuroinflammation, UCL Institute of Neurology, London, UK; 2Computer Science, University College London, London, UK

The feasibility to relate parameters derived from axial Diffusion Imaging of the cervical spinal cord to the vertebral level of the acquisition was investigated. Two slices were acquired at different levels of C3. The first slice was positioned where fibres of the ventral root were identified in the T1 weighted image, the second were no sprouting fibres were observed. Results suggest that the estimated diffusion parameters are sensitive to the position of the slice. A second scan of the same subject at a different time was able to reproduce the results of the first scan.

14:30         3192.     Acute in Vivo DTI Predicts Chronic Neurological Disability in Rats Suffering Traumatic Spinal Cord Injury

Joong H. Kim1, David K. S. Magnuson2, Sheng-Kwei Song1

1Radiology, Washington University, St. Louis, MO, USA; 2Neurological Surgery and Anatomical Sciences & Neurobiology, University of Louisville, Louisville, KY, USA

Acute in vivo DTI was performed on rats suffering contusive injury at thoracic cord with a 4.7 T magnet. The high resolution DTI maps sensitively reflected injury severity of white matter accurately correlating with neurological functions assessed chronically. These preliminary results suggested that in vivo DTI derived parameters effectively reflecting spinal cord white matter injury and predicting long term neurological outcome.

15:00         3193.     Vascular Modulation of SCI: A Longitudinal MRI Study

Laura Sundberg1, Juan Herrera1, Ponnada Narayana1

1Diagnostic and Interventional Imaging, The University of Texas Medical School, Houston, TX, USA

Angiogenesis, an essential component of wound repair, is known to occur in response to spinal cord injury (SCI), yet its role in neurological recovery is controversial. The purpose of these studies was to modulate angiogenic activity, via direct epicenter administration of VEGF, a potent pro-angiogenic factor, or anti-VEGF to suppress angiogenic activity, and investigate the outcome in experimental SCI using in vivo longitudinal MRI. Lesion volume was determined by high resolution anatomical MRI to evaluate the evolution of the lesion over a period of 56 days and the data was correlated with a variety of neurobehavioral and neurosensory assays.

 


 
Multiple Sclerosis & White Matter Imaging
Exhibit Hall 2-3                    Monday 14:00-16:00          Computer 6

14:00         3194.     High Resolution White Matter T1 Mapping in Multiple Sclerosis at 7T

Ali Mohammad Al-Radaideh1, Matthew J. Brookes1, Olivier Mougin1, Emma C. Tallantyre2, Nikos Evangelou2, Su-Yin Lim2, Alain Pitiot3, Cris Constantinescu2, Paul S. Morgan4, Peter G. Morris1, Penny A. Gowland1

1Sir Peter Mansfield Magnetic Resonance Centre, The University Of Nottingham, Nottingham, UK; 2Clinical Neurology, The University Of Nottingham, Nottingham, UK; 3Brain and Body Centre, The University Of Nottingham, Nottingham, UK; 4Medical University Of South Carolina, USA

Previous literature has shown that the T1 distribution of healthy appearing white matter (WM) in the brains of MS patients is shifted relative to that of healthy control subjects. In this study, we measure the distribution of T1 values at 7T. Our results suggest that there is a difference in T1 histograms between WM in MS patients and WM in normal volunteers. Further, the areas of highest T1 appear close to the site of MS lesions. Future study of this effect may result in T1, and spatial distribution of high T1 values, becoming a marker of disease progression in MS.

14:30         3195.     NAWM Changes as Assessed by Q-Space Analysis Correlate Inversely with T1- And T2-Lesion Volumes in MS Patients

Katrin Weier1, Eli Renate Gruener2, Jochen G. Hirsch3, Matthias Guenther4, Michael Amann3, Ludwig Kappos1, Ernst-Wilhelm Radue, Achim Gass3

1Neurology, University Hospital Basel, Basel, Switzerland; 2Radiology, Haukeland University Hospital, Bergen, Norway; 3Neurology/Neuroradiology, University Hospital Basel, Basel, Switzerland; 4MR Research Neurology, University Hospital Mannheim, Mannheim, Germany

The detection of abnormality in the NAWM of MS patients is challenging.

15:00         3196.     Diffusion Tensor Tractogrpahy Quantification of Wallerian Degeneration of the Uncinate Fasciculus in Multiple Sclerosis

Khader M. Hasan1, Arash Kamali2, Amal Iftikhar1, Sushmita Datta1, Flavia Nelson3, Jerry S. Wolinsky1, Ponnada A. Narayana1

1Diagnostic and Interventional Imaging, University of Texas Health Science Center at Houston, Houston, TX, USA; 2Diagnostic and Interventional Imaging, University of Texas Health Science Center at Hosuton, Houston, TX, USA; 3Neurology, University of Texas Health Science Center at Houston, Houston, TX, USA

Previous multiple sclerosis studies have not considered association pathways such as the uncinate fasciculus (UF) which is the largest white matter pathway that directly connects temporal and frontal lobe. The UF has been implicated in several clinical DTI studies using two-dimensional regions-of-interest which could not reliably assess the entire 3D tract. In this report, we demonstrate using diffusion tensor tractography (DTT) of the normal-appearing uncinate fasciculus (UF) combined with whole brain lesion load measurements, the utility of DTI tractography in quantifying hallmarks of Wallerian degeneration in relapsing-remitting MS (RRMS).

15:30         3197.     Proton Magnetic Resonance Spectroscopy for Monitoring Disease Progression and Response to Treatment in Multiple Sclerosis

Sanjeev Chawla1, Sumei Wang1, Ragini Verma1, Elias R. Melhem1, Clyde Markowitz2, Harish Poptani1

1Radiology, University of Pennsylvania, Philadelphia, PA, USA; 2Neurology, University of Pennsylvania, Philadelphia, PA, USA

Multivoxel proton magnetic resonance spectroscopic imaging was performed on ten patients with multiple sclerosis (MS) and ten controls in a longitudinal study. Normal appearing white matter (NAWM) from controls and thirty-four MS plaques along with one-voxel thick NAWM regions surrounding plaques at each time point were analyzed. Significant reduction in NAA along with elevations in Cho and mI were observed in patients (at baseline) compared to controls. Within MS patients, NAA reduced initially followed by a slow recovery both within plaques and in NAWM. Significant elevation in Cr and mI were observed in subsequent months both within plaques and NAWM.

 
Exhibit Hall 2-3                    Tuesday 13:30-15:30          Computer 6

13:30         3198.     MRI Metrics of Nonlinear Atrophy in MS Disease Progression

Dominik S. Meier1, Charles R.G. Guttmann1

1Radiology, Brigham & Women's Hospital - Harvard Medical School, Boston, MA, USA

Global brain parenchymal atrophy, assessed from structural brain MRI, has become established as reliable metric of progression in many neurodegenerative diseases. Uncertainty remains to what extent this measure expresses nonlinearity over time and to what extent current methods are sensitive to capture nonlinear behavior. We tested nonlinearities in BPF change in multiple sclerosis (MS) over time and the impact on predicting disease progression. Linear models tended to overestimate atrophy at 3-5 year follow-up. Nonlinear models achieved significantly better fits. A greater atrophy rate in the first year was associated with a higher number of attacks.

14:00         3199.     In Vivo GABA Measurement in MS Sensorimotr Cortex -- A Marker for Disease Progression?

Pallab K. Bhattacharyya1, Robert Bermel2, Micheal Phillips1, Lael Stone2, Mark Lowe1

1Imaging Institute, Cleveland Clinic, Cleveland, OH, USA; 2Neurological Institute, Cleveland Clinic, Cleveland, OH, USA

Recent histopathological data have demonstrated that GABA levels are markedly reduced in MS patients in comparison to healthy controls. We have performed in vivo GABA measurement of sensorimotor cortex for both healthy controls and MS patients at 3 tesla. We found a drop in the cortical GABA level in MS patients. In addition, our preliminary data suggest an inverse correlation between manual task performance and GABA level in MS patients. Our preliminary observation indicates that reduced cortical GABA concentration reflects disease burden.

14:30         3200.     Tactile-Associated Recruitment of Cervical Cord Is Altered in MS Patients with Fatigue

Martina Absinta1,2, Maria Assunta Rocca1,2, Giulia Longoni1,2, Paola Valsasina1, Federica Agosta1, Domenico Caputo3, Massimo Filippi1,2

1Neuroimaging Research Unit, Scientific Institute Hospital San Raffaele, Milan, Italy; 2Department of Neurology, Scientific Institute Hospital San Raffaele, Milan, Italy; 3Department of Neurology, Scientific Institute Fondazione Don Gnocchi, Milan, Italy

Cervical cord activations in relapsing-remitting (RR) multiple sclerosis (MS) patients with fatigue were compared with RRMS without fatigue and healthy controls. Subjects were scanned when performing a sensory task (tactile stimulation of right hand). Statistical activity maps were generated and the presence of activity in each cord region was assessed. RRMS without fatigue showed higher fMRI cord activity compared with controls, while RRMS with fatigue did not. RRMS with fatigue had a more widespread pattern of regional activity both than controls and RRMS without fatigue. In MS, fatigue is associated with reduction of cord recruitment and loss of its lateralization.

15:00         3201.     Identification of Benign Multiple Sclerosis Using Whole Brain N-Acetylaspartate

Daniel Rigotti1, Robert I. Grossman1, Beatrice Benedetti2, Andrea Falini3, Massimo Filippi2, Oded Gonen1

1Radiology, NYU School of Medicine, New York, NY, USA; 2Neurology, San Raffaele Scientific Institute and University, Milan, Italy; 3Neuroradiology, San Raffaele Scientific Institute and University, Milan, Italy

WBNAA concentration was measured in 44 patients with benign multiple sclerosis (B-MS) using an unlocalized 1H-MRS sequence. Conventional dual echo T1-weighted scans were obtained to measure normalized brain volume. The annual rate of decline of WBNAA in B-MS patients is similar to that of moderately declining relapsing-remitting MS (RR-MS) patients. This suggests that there is a) no predictable method for prognosis triaging between moderate and benign patients and b) neuronal loss is globally similar in the two groups, but the preservation of more eloquent areas in b-MS patients may be more prevalent.

 
Exhibit Hall 2-3                    Wednesday 13:30-15:30          Computer 6

13:30         3202.     Brain Dynamic Susceptibility Contrast Perfusion Imaging Histograms in Primary Progressive Multiple Sclerosis

Behrang Amini1, Glyn Johnson2, James S. Babb2, Joseph Herbert3, Robert I. Grossman4, Matilde Inglese5

1Radiology, Tufts Medical Center, Boston, MA, USA; 2Radiology, New York University, New York, NY, USA; 3Neurology, New York University, New York, NY, USA; 4Dean's Office, New York University, New York, NY, USA; 5Radiology and Neurology, New York University, New York, NY, USA

Perfusion MRI studies in MS have identified regional areas of decreased perfusion in grey matter (GM) and white matter (WM), but the pattern in clinical subgroups is unclear. Our study investigated global GM and WM perfusion changes in patients with primary-progressing MS (PP-MS) using dynamic susceptibility contrast perfusion MRI and the histogram approach. The results from eight PP-MS patients and eight healthy controls are presented. Although the difference did not reach statistical significance, both global GM and WM perfusion were lower in patients compared to controls. The study is ongoing and data from a larger sample size will be presented.

14:00         3203.     Influence of Hypointense White Matter Lesions in Segmentation Based Assessment of Brain Volume. Implications for Clinical MS Studies.

Marco Battaglini1, Antonio Giorgio2, Maria Laura Stromillo2, Nicola De Stefano2

1Department of Neurological and Behavioral Sciences , University of Siena, Siena, Toscany, Italy; 2Department of Neurological and Behavioral Sciences, University of Siena, Siena, Toscany, Italy

Brain atrophy is an important marker for disease progression in multiple sclerosis (MS). The influence of T1 hypointense lesions on compartimental brain volumes was tested on 5 patients. Percent volume differences of normalised cortical grey matter (NC-PVDs) and white matter (NW-PVDs) between T1-W images with very low lesion volume (LV) and T1-W images with increasing LV and different lesion intensity (LI) were computed. With increasing LV, NCV was underestimated for LI between GM and WM LI. LV and LI of T1 hypointense lesions should be considered when using segmentation-based algorithms for brain volumes’ quantification.

 

14:30       3204.       WITHDRAWN

 

15:00         3205.     Semi-Automated Segmentation of Microhemorrhages Revealed by SWI

Randall R. Benson1, Ramtilak Gattu2, Balaji Myrtheunjayan3, Zhifeng Kou4, Ewart M. Haacke4

1Neurology, Wayne State University, Detroit, MI, USA; 2Radiology, Wayne State University/MR Research Facility, Detroit, MI , USA; 3Biomedical Engineering, Wayne State University, Detroit, MI, USA; 4MR Research Facility, Wayne State University, Detroit, MI, USA

Until now neuropsychological and cognitive deficits in treated PKU patients could not be correlated to their known brain lesions found in conventional MRI. In this work, in addition to the findings that the brain lesions are not corresponding to the therapeutic compliance of the patients, microstructural changes in normal appearing brain tissue in treated PKU patients are disclosed by using quantitative proton/T2-mapping and DTI, which may indicate a global neurotoxic effect of the elevated phenylalanine levels, and contributes to the understanding of the pathomechanisms in PKU patients. Conventional MRI is insensitive to milder traumatic brain injury. Susceptibility-weighted imaging (SWI) has demonstrated superior sensitivity to microhemorrhages in TBI. Manual lesion counting is labor intensive and operator dependent. Automated methods offer many advantages. The current study summarizes our recent efforts to develop an automated method of lesion segmentation and quantification. The method relies on intensity based probability mapping along with masking the major sources of false positive artifact. Results from 16 TBI patients demonstrate the feasibility, accuracy and clinical correlation of the method.

 
Exhibit Hall 2-3                    Thursday 13:30-15:30          Computer 6

13:30         3206.     Application of the Diffusion Standard Deviation Map for Detection of White Matter Reorganization After Stroke

Siamak Pourabdollah-Nejad1,2, David Hearshen3, Quan Jiang1,4, Douglas Noll2, Panayiotis Mitsias1, Brian Silver1, Michael Chopp1

1Department of Neurology, Henry Ford Hospital, Detroit, MI, USA; 2Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; 3Department of Radiology, Henry Ford Hospital, Detroit, MI, USA; 4Department of Physics, Oakland University, Rochester, MI, USA

We demonstrate the application of a novel anisotropy map for monitoring white matter recovery in stroke patients. The new map termed Standard Deviation (SD) map is based on calculating the standard deviation of diffusion using diffusion q-ball MRI. SD map for a stroke patient has been created and validated using the q-ball orientation distribution function map. The results show that this map is able to identify white matter reorganization in recovering brain regions predominated with crossing fibers. This makes this map more reliable than the standard Fractional Anisotropy map for identifying these brain regions.

14:00         3207.     Design of a SAR Compatible, 3T QMTI Protocol

Claudiu Schirda1,2, Alexey Samsonov3, Jennifer L. Cox1,2, Robert Zivadinov1,2

1Buffalo Neuroimaging Analysis Center, Buffalo, NY, USA; 2Department of Neurology, The Jacobs Neurological Institute, SUNY Buffalo, Buffalo, NY, USA; 3Department of Radiology, University of Wisconsin-Madison, Madison, WI, USA

Typical magnetization transfer (MT) techniques use a pair of sequences, with and without the MT pulse, and an MT Ratio (MTR) is calculated. This ratio is sensitive to the macromolecular content but it also depends on the T1 relaxation properties of the tissue. Quantitative Magnetization Transfer Imaging (qMTI) removes this drawback, by measuring and accounting for the T1 relaxation effect. However, at higher magnetic fields, due to the quadratic increase with B0 in RF power deposited by the MT pulse, SAR becomes an important limitation. We demonstrate the design of a 3T qMTI protocol compatible with the First Level SAR limit.

14:30         3208.     Proton Metabolite Changes in the Corpus Callosum, Thalamus and Brainstem Following Traumatic Brain Injury

Varan Govind1, Krithica Kaliannan1, Gaurav Saigal1, Stuart Gold2, Jonathan Jagid3, Leo Harris1, Andrew A. Maudsley1

1Radiology, University of Miami, Miami, FL, USA; 2Jackson Memorial Hospital, Miami, FL, USA; 3Neurosurgery, University of Miami, Miami, FL, USA

Regions-of-interest analyzes of whole-brain MRSI data from the corpus callosum, thalamus and midbrain indicate significant changes of proton metabolite values or their ratios following traumatic brain injury. Relationships between the metabolite changes and neuropsychological test scores were tested for their associations and found no significant correlations between them, suggesting that the underlying metabolite alterations in these structures cannot be specifically associated with cognitive deficits as determined from the neuropsychological testing.

15:00         3209.     Multimodality Imaging of Cerebral Schistosomiasis

Albert J.S. Idema1, Joyce Wilbers2, P. Krooshof3, A. C. Koetsveld1, P. Wesseling4, W. van der Graaf5, A. Gijtenbeek2, W. Oyen6, A. Heerschap7

1Neurosurgery, UMC St Radboud, Nijmegen, Gelderland, Netherlands; 2Neurology, UMC St Radboud, Netherlands; 3Analytical Chemistry, Institute for Molecules and Materials, Nijmegen, Netherlands; 4Pathology, UMC St Radboud, CWZ, Netherlands; 5Medical Oncology, UMC St Radboud, Netherlands; 6Nuclear Medicine, UMC St Radboud, Netherlands; 7Radiology, UMC St Radboud, Netherlands

In this case report we describe multimodality imaging of neuroschistosomiasis. Besides conventional MRI, this patient was examined with perfusion imaging, short-echo time 3D MR Spectroscopy and 18F-Fluorothymidine PET imaging. The histopathological findings in a biopsy were used to explain the imaging results. An increased FLT activity and lactate, next to a strong NAA decrease may point to a malignant process, however, the minimal increased Choline and perfusion indicate otherwise. Increased levels of glutathione and aspartate may be typical for this lesion. FLT-PET seems not be able to discriminate between active proliferating inflammatory cells and proliferating tumor cells in the brain.

 


 
Advanced Imaging in MS
Exhibit Hall 2-3                    Monday 14:00-16:00          Computer 7

14:00         3210.     In Vivo Multislice Mapping of Myelin Water Content of the Brain with T2* Signal Decay

Dosik Hwang1, Yiping P. Du2

1Electrical and Electronic Engineering, Yonsei University, Seoul, Korea; 2Psychiatry, University of Colorado Denver, Denver, CO, USA

In vivo myelin water content was successfully estimated using T2* relaxation with multislice acquisitions. The advantages of using T2* are (1) low specific absorption rate, (2) short first echo time (~2ms) and short echo spacing (~1ms), (3) fast multislice acquisitions up to 8 slices in high resolution (256 x 256) (24 slices could be possible). An adequate temporal SNR for the exponential fitting was achieved with use of an 8-channel phased-array coil. The optimal T2* range for the myelin water signal was found from 3 to 23 ms. Multislice high-resolution myelin maps were obtained in 8.5 minutes.

14:30         3211.     Comparison of Myelin Water Fraction in Cross-Regularized T1-Relaxograms of Normal White Matter at 3T and 7T and of Normal-Appearing White Matter at 3T

Christian Labadie1,2, Derek V. Ott1, Thies H. Jochimsen1, Jing-Huei Lee3, Harald E. Möller1,2

1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; 2Faculty of Physics and Earth Science, University of Leipzig, Germany; 3Biomedical Engineering, University of Cincinnati, OH, USA

The myelin water fraction (MWF) measured by cross-regularized T1-relaxography exhibits an increase between 3T and 7T in the white matter of a healthy volunteer. The field dependency of MWF and T1 allowed an estimation of the exchange of water between myelin and the axonal space with a mean resident time of water in myelin of 666.4 ± 369.5 ms. A preliminary study of lesions and normal-appearing white matter in an MS-patient suggests a slight change in the bimodal distribution of MWF.

15:00         3212.     T2 Distribution Reflects Multiple Sclerosis Pathologies: Histology Driven Regions of Interest

Thorarin A. Bjarnason1, Cornelia Laule2, Esther Leung2, J Ross Mitchell1, Piotr Kozlowski2, Alex L. MacKay2, G. R. Wayne Moore2

1University of Calgary, Calgary, AB, Canada; 2University of British Columbia, Vancouver, BC, Canada

T2 distributions created from multi-echo T2 acquisitions are sensitive to changes in various water environments. Understanding how the T2 distribution changes in the presence of specific MS pathologies may help identify those pathologies in-vivo. We used histological stains for myelin and axons to drive region of interest placement on fixed brain multi-echo T2 MR images. In addition to changes in the myelin water fraction, we observed a lengthening of the intra/extracellular water geometric mean T2 times from regions found in the histology stains having normal appearing white matter, reduced Luxol Fast Blue and reduced Bielschowsky stain intensities, to lesions.

15:30         3213.     Myelin Sensitive Multi-Component DESPOT Imaging in Multiple Sclerosis

Hagen H. Kitzler1, Sean C. Deoni2,3, Cyndi Harper-Little1, Andrew Leung4, Marcelo Kremenchutzky5, Brian K. Rutt1

1Robarts Research Institute, University of Western Ontario, London, Ontario, Canada; 2Centre for Neuroimaging Research, Institute of Psychiatry, King's College London, London, UK; 3Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, Oxford, UK; 4Department of Diagnostic Radiology and Nuclear Medicine, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada; 5Department of Clinical Neurological Sciences, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada

This study used a novel quantitative myelin-sensitive MR imaging method known as multi-component Driven Equilibrium Single Pulse Observation (mcDESPOT) to explore changes in Normal Appearing White Matter (NAWM) in early and late stages of MS development. The exploration of comparative histogram and ROI analyses of the myelin volume fraction (VFM) a parameter derived by mcDESPOT data processing revealed a promising trend towards a correlation of the measured VFM with the stage of disease development and clinical disability in a spectrum of different types of MS.

 
Exhibit Hall 2-3                    Tuesday 13:30-15:30          Computer 7

13:30         3214.     Increased Anisotropy in Subcortical Gray Matter Structures: A Neurodegeneration Marker in Multiple Sclerosis.

Salem Hannoun1,2, Francoise Durand-Dubief1,3, Danielle Ibarrola2, Jean Christophe Comte2, Christian Confavreux3, Dominique Sappey-Marinier1,2

1CREATIS-LRMN, UMR5220 CNRS & U630 INSERM & Université de Lyon, Bron, France; 2CERMEP-Imagerie du vivant, Bron, France; 3Hopital Neurologique, Groupement Hospitalier Est, Bron, France

The aim of this work is to provide new markers of neurodegenerative processes in Multiple Sclerosis (MS) using DTI. Axial (ëa) and radial (ër) diffusivities as well as FA and ADC have been extracted from subcortical gray matter (SGM) structures (thalamus, caudate and lenticular nuclei). Our results, obtained in 62 patients with different clinical forms, showed significant increase of FA and ëa values in SGM structures. This alteration is particularly significant in patients with primary progressive form of MS which may suggest a loss of dendritic branching resulting from early neurodegenerative processes.

14:00         3215.     Diffuse Subclinical Disease Activity in Normal-Appearing White Matter During Remission in Multiple Sclerosis: A Proton MR Spectroscopy Study

Ivan I. Kirov1, Vishal Patil1, James Babb1, Henry Rusinek1, Joseph Herbert2, Oded Gonen1

1Radiology, NYU SOM, New York, NY, USA; 2Neurology, NYU SOM, New York, NY, USA

To test the hypothesis that widespread chronic pathogenesis precedes axonal damage in MRI normal-appearing tissue in relapsing-remitting MS, we used 3D proton MR spectroscopy at 3 T to quantify the concentrations of NAA, Cr, Cho and mI in a 360 cm3 volume of interest (VOI) about the corpus callosum (mostly white matter). Twenty-one “recently diagnosed” mildly disabled patients and 15 matched controls were enrolled. The results reveal that patients’ VOI tissue volume fraction and NAA concentration were not different from controls’. In contrast, the patients’ Cr, Cho and mI levels were 9%, 14% and 20%, higher than the controls’.

14:30         3216.     Diffusion Tensor MRI Study of the Spinal Cord in Patients with Multiple Sclerosis

Jan von Meyenburg1, bertram Wilm2, anja Weck3, evelyn Gallus1, Elisabeth Schätzle1, Peter Boesiger2, Norbert Goebels3, Spyros S. Kollias1

1Institute of Neuroradiology, University Hospital Zürich, Zürich, Switzerland; 2Institute for Biomedical Engineering, University & ETH Zürich, Zürich, Switzerland; 3Department of Neurology, University Hospital Zürich, Zürich, Switzerland

Diffusion tensor imaging of 18 volunteers and 41 patients with relapsing remitting Multiple sclerosis (MS), secondary progressive MS or primary progressive MS was acquired at three levels (cervical, thoracic, lumbar enlargement) of the spinal cord. Diffusivity values were evaluated in normal appearing posterior white matter (PWM). Fractional anisotropy in cervical PWM was highest in healthy volunteers and lowest in PPMS patients. Mean apparent diffusion coefficient was lowest in volunteers and highest in RRMS patients. Neuropathological changes might be responsible for the difference of diffusivity values between MS-types. Furthermore the anisotropy values suggest that axonal loss decreases in a cranio-caudal sense.

15:00         3217.     Accurate Estimation of Tissue Volumes by Means of Quantitative MR on Patients with Multiple Sclerosis

Janne West1,2, Jan B. Warntjes2,3, Peter Lundberg1,2, Anne Marie Landtblom4

1Department of Medicine and Health, Division of Radiation Physics, Linköping, Sweden; 2Center for Medical Imaging Science and Visualization, Linköping, Sweden; 3Department of Medicine and Health, Division of Clinical Physiology, Linköping, Sweden; 4Department of Clinical and Experimental Medicine, Division of Neurology, Linköping, Sweden

Using quantitative MRI the tissue specific parameters R1, R2 and PD (R1=1/T1, R2=1/T2) are quantified. It is shown that volume fraction of tissues in a voxel can be related to R1, R2 and PD measurements. Using this method it is possible to accurately calculate tissue volumes on a sub-voxel scale. This method were used in a group of patients with Clinically Definite Multiple Sclerosis (CDMS) to asses tissue volumes of white matter (WM), gray matter (GM), cerebrospinal fluid (CSF) and MS plaque for whole brain coverage.

 
Exhibit Hall 2-3                    Wednesday 13:30-15:30          Computer 7

13:30         3218.     Hydration Status Does Not Affect Brain Water Content or Myelin Water Fraction in Healthy Volunteers

Irene Margaret Vavasour1, Cornelia Laule1, Shannon H. Kolind2, Roger Tam1, Jimmy Lee3, Burkhard Maedler4, Anthony L. Traboulsee3, David K. Li1, Alex L. MacKay1,2

1Radiology, University of British Columbia, Vancouver, British Columbia, Canada; 2Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, Canada; 3Medicine, University of British Columbia, Vancouver, British Columbia, Canada; 4Phillips Healthcare, Vancouver, British Columbia, Canada

As the magnetic resonance signal is primarily from water, a person’s hydration status could potentially influence the values of MR parameters from brain. In this study, histograms of water content, myelin water fraction, T1 and T2 were obtained from brain in 20 healthy volunteers in four acquisitions: before and after drinking 3 litres of water and two scans after fasting for 9 hours. No significant differences were found between the MR parameter histograms from the four sessions, indicating that brain hydration was affected minimally by the protocol.

14:00         3219.     Histograms of Multi-Component T2 Relaxation Imaging in Multiple Sclerosis: Characterization and Comparison with Histograms from Diffusion Tensor Imaging.

Shannon Heather Kolind1, Cornelia Laule, Irene Vavasour, Burkhard Mädler2, Alexander Rauscher, Virginia Devonshire, John Hooge, Joel Oger, Penelope Smyth, Anthony Traboulsee, Wayne Moore, David Li, Alexander MacKay

1Physics, University of British Columbia, Vancouver, BC, Canada; 2Philips Medical Systems, Vancouver, BC, Canada

Using a recently developed 3D multi-echo T2 relaxation sequence for increased brain coverage, we conducted histogram analysis for a more thorough characterization of myelin water fraction (MWF, the short T2 component of water in brain associated with myelin) in multiple sclerosis (MS) brain than has previously been possible. We also investigated the relationship between MWF and diffusion tensor imaging (DTI) measures. Thirteen MS patients and 11 controls underwent T2 relaxation and DTI examinations to create histograms for white matter and lesion. MS MWF histograms differed considerably from those of controls, however, differences did not mirror those observed in DTI histograms.

14:30         3220.     MRI Evidence That Gadolinium-Enhancing Lesions Seen Twelve Weeks After Commencing Rituximab Treatment Are Associated with Lower Blood-Brain-Barrier Disruption Than Those Seen Prior to Treatment in Patients with Relapsing-Remitting Multiple Sclerosis

Zografos Caramanos1,2, Ilana Leppert1, Sridar Narayanan1,2, G Bruce Pike1, Douglas Lorne Arnold1,2

1McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; 2NeuroRx Research, Montreal, Quebec, Canada

Building on previous findings that treatment with rituximab results in decreased gadolinium-enhancing (<B>Gd+</B>) lesion counts and volumes in patients with relapsing-remitting multiple sclerosis (<B>MS</B>), we found evidence that Gd+ lesions seen twelve weeks post-rituximab exhibit significantly lower blood-brain barrier (<B>BBB</B>) disruption than those seen pre-treatment. This suggests that a continuous classification of BBB disruption in patients with MS may reveal treatment-related changes that are not detected by the conventional, binary classification of lesions as being Gd+ or not. Furthermore, our results suggest that the practical measure of BBB disruption that we used can provide additional information that is independent of that provided by Gd+ lesion volume.

15:00         3221.     Serial Susceptibility Weighted (Phase) Imaging in Multiple Sclerosis

Alexander Rauscher1,2, Irene Vavasour3, Cornelia Laule3, Shanon Kolind4, Talia Vertinsky3, Wayne Moore5, Burkhard Mädler6, Joel Oger7, Anthony Traboulsee7, Davi Li3, Alex MacKay1

1UBC MRI Research Centre, University of British Columbia, Vancouver, British Columbia, Canada; 2Radiology, University of British Columbia; 3Radiology, University of British Columbia, Vancouver, British Columbia, Canada; 4Physics, University of British Columbia, Vancouver, British Columbia, Canada; 5Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada; 6Philips Healthcare, Vancouver, British Columbia, Canada; 7Neurology, University of British Columbia, Vancouver, British Columbia, Canada

Multiple sclerosis is a recurrent and chronic inflammatory disease of

 
Exhibit Hall 2-3                    Thursday 13:30-15:30          Computer 7

13:30         3222.     Comparing SWI and R2’ for the Detection of Iron Deposition in MS

Kecheng Liu1, Michael Phillips2, Jian Lin2, Lael Stone2, Robert Bermel2, Erik Beall2, Mark J. Lowe2

1MR, Siemens Medical Solutions, USA Inc, Malvern, PA, USA; 2Cleveland Clinic, Cleveland, OH, USA

It has been shown that iron content measuring and SWI are sensitive to the characteristics of multiple sclerosis (MS) lesions, in particular iron content. Based on the observation that SWI can detect lesions not apparent on conventional MS lesion screening protocols, it has been suggested that there may be additional clinical utility in characterizing lesions by their iron content. In addition, it has been shown that SWI is sensitive to increased iron in the basal ganglia and other subcortical regions in MS. We propose to study the clinical utility of SWI and other iron-content sensitive methods, such as R2' and T2 mapping, in MS. In this work, we show that, although both have a high sensitivity to iron content, R2’ imaging provides more specificity to iron content in MS patients than SWI.

14:00         3223.     Multiple Sclerosis Lesions at 3T. Scalars and Fibers.

Mustafa Okan Irfanoglu1, Steffen Sammet1, Raghu Machiraju1, Michael` V. Knopp1

1Department of Radiology, The Ohio State University, Columbus, OH, USA

Diffusion Tensor Imaging has proved to be very useful in early diagnosis of Multiple Sclerosis. In this work, we analyze the properties of fractional anisotropy, trace and fiber lengths on lesion locations, normal appearing white matter and healthy brain regions. By using this knowledge, we employ a statistical inference scheme to help detection of candidate lesion locations.

14:30         3224.     Directional Diffusivities in Human Spinal Cord Correlate with Functional Outcome

Junqian Xu1, Eric C. Klawiter1, Tammie L.S. Benzinger2, Robert T. Naismith1, Sheng-Kwei Song2, Anne H. Cross1

1Neurology, Washington University in St. Louis, St. Louis, MO, USA; 2Radiology, Washington University in St. Louis, St. Louis, MO, USA

Axial and radial diffusivities were quantified in the spinal cord white matter tracts of six stable multiple sclerosis (MS) patients with good recovery and two stable neuromyelitis optica patients with poor recover. Results were compared with that from seventeen healthy volunteers. Between the good recovery MS group and the normal control group, no significant differences in axial diffusivity were observed, suggesting little permanent axonal damage in these MS patients; while radial diffusivity increased moderately in the MS group compared to control, suggesting incomplete remyelination. In the two NMO patients with poor recovery, dramatically increased radial diffusivity in the center of the lesion (both located in posterior column) indicates severe tissue demyelination correlating with loss of vibration perception; while decreased axial diffusivity and increased radial diffusivity in the normal appearing cortical spinal tracts correlated with motor function measures, such as, muscle test, 9-hole peg test, and 25-foot timed walk.

15:00         3225.     Depiction of Cortical Lesions in Multiple Sclerosis at 7T: Comparison with Immunohistochemistry

Petra Schmalbrock1, Francisco Aguila1, David Pitt2, Aaron Boster2, Michael Racke2, Kottil Rammohan2, Wei Pei2, Steffen Sammet1, Michael Vincent Knopp1

1Radiology, The Ohio State University, Columbus, OH, USA; 2Neurology, The Ohio State University, Columbus, OH, USA

Depiction of cortical lesions in Multiple Sclerosis is of significant interest. With its increased SNR and spatial resolution, 7T MRI is uniquely suited for this task. The objective of our study was to test and validate with pathology different sequences with spatial resolution ranging from those feasible in vivo to ultra-high resolution scans over several hours. Lesion contrast was best with a white matter attenuated turbo-field echo sequence which, at high spatial resolution, yielded the highest lesion count, even though SNR was lower compared to susceptibility-weighted MRI. SWI performed well for depiction of mixed lesions, but not intracortical lesions.

 


 
Advanced Imaging in Normal Aging
Exhibit Hall 2-3                    Monday 14:00-16:00          Computer 8

14:00         3226.     Calibrated FMRI Reveals Altered Neurovascular Coupling with Age During a Cognitive Stroop Task

Laura M. Parkes1, Guy Lumley2, Rafat S. Mohtasib2, Hedley Emsley3, Jonathan A. Goodwin2

1Imaging Sciences and Biomedical Engineering, University of Manchester, Manchester, UK; 2Magnetic Resonance and Image Analysis Research Centre, University of Liverpool, UK; 3Department of Neurology, Royal Preston Hospital, UK

Calibrated fMRI allows quantitative estimates of the relative changes in cerebral metabolic rate of oxygen (ÄCMRO2) and cerebral blood flow that accompany neural activation. In this study we consider differences in these measures between a young and a healthy old group during a cognitive Stroop task using hyperoxia calibration. The BOLD response to hyperoxia was reduced in the older group, leading to a reduction in calibration constant ‘A’ in all regions which we believe relates to a reduction in blood volume. ÄCMRO2 was also lower in all regions in the older group, despite increased BOLD response in frontal regions.

14:30         3227.     Age-Related Increases in Spatial Variability of FMRI-BOLD Activation Is Neural or Vascular in Origin

Sridhar S. Kannurpatti1, Michael A. Motes2, Bart Rypma2, Bharat B. Biswal1

1Radiology, UMDNJ-New Jersey Medical School, Newark, NJ, USA; 2School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA

As a person ages, dramatic neural plasticity occurs leading to differences in the amplitude and spatial extent of task-induced functional Magnetic Resonance Imaging (fMRI) responses and presents challenges of estimating altered activation due to disease. fMRI-BOLD studies were conducted in older and younger subject groups using a motor, cognitive and a breath hold task. We observed a decrease in average area of activation during the motor, cognitive or the BH task in the elderly, which was mainly due to a relatively larger spatial variability in activation. Based on our results on the larger spatial variability in activation in the elderly over the motor, cognitive and BH tasks, we propose the hypothesis that normal aging may spatially rearrange brain function in a subtle manner depending on existing areas of efficient cerebrovascular function.

15:00         3228.     Age Effects on Low Frequency Physiological Fluctuations in Resting BOLD FMRI

Lirong Yan1, Yan Zhuo1, Bo Wang1, Rong Xue1, Geoffrey Aguirre2, Jiongjiong Wang3

1State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, CAS, Beijing, China; 2Neurology, University of Pennsylvania, Philadelphia, PA, USA; 3Radiology, University of Pennsylvania, Philadelphia, PA, USA

The purpose of this study was to test the hypothesis whether the magnitude of low frequency fluctuations (<0.1Hz) in resting BOLD fMRI can be used to study aging effects. Multi-echo BOLD fMRI data were acquired both during resting state and visual stimulation in young and elderly healthy subjects. There were linear correlations between BOLD signal changes during activation and low frequency physiological fluctuations at rest in both age groups. And the association between BOLD activation and low frequency fluctuation was stronger in the young group than in the elderly group both across subjects and across activated pixels in visual cortex.

15:30         3229.     Lateralization of Language Pathways During Adolescence and Early Adulthood

Luca Pugliese1,2, Flavio Dell'Acqua1,2, Michel Thiebaut de Schotten2, Sanja Budisavljevic2, Steve Williams3, Declan Murphy1, Marco Catani1,2

1Psychological Medicine, Section of Brain Maturation, Institute of Psychiatry, London, UK; 2Natbrainlab, section of Brain Maturation, Institute of Psychiatry, London, UK; 3Center of Neuroimaging Science, Institute of Psychiatry, London, England, UK

During adolescence a number of genetic, hormonal, and environmental factors contribute to significant modifications of the human brain anatomy. Modifications in white matter tracts are of particular importance as these may underlie the acquisition of specific cognitive functions. Here we used diffusion tensor imaging tractography to study the lateralization of the perisylvian pathways from late childhood to early adulthood. Results suggest that lateralization of the most posterior part of the arcuate fasciculus occurs during adolescence, probably due to reorganization of white matter connections in the right hemisphere. Other tracts are already lateralized before adolescence suggesting an early development in life.

 
Exhibit Hall 2-3                    Tuesday 13:30-15:30          Computer 8

13:30         3230.     Age and Gender Related Changes of Human Brains Using Magnetic Resonance Hybrid Diffusion Imaging

Yu-Chien Wu1,2, Frances B. Haeberli2, Aaron S. Field1,3, Andrew L. Alexander2,4

1Radiology, University of Wisconsin-Madison, Madison, WI, USA; 2Waisman Laboratory for Brain Imaging & Behavior, University of Wisconsin-Madison, Madison, WI, USA; 3Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA; 4Medical Physics, University of Wisconsin-Madison, Madison, WI, USA

Diffusion spectrum imaging is a model-free and more generalized approach to describe water diffusion function, PDF, in complex brain tissues. In this study, hybrid diffusion imaging (HYDI) was used to estimate PDF and DTI measures across 52 human brains with an age span of 18-72 years-old. Age and gender effects were investigated on both the PDF and DTI measures, including Po, MSD, FA, MD, Da, Dr. The investigation was done in native space where white and gray matters were segmented. Little, but significant age and gender related changes were found. Furthermore, WM volume-ratio increases while GM decreases as age increases.

14:00         3231.     A Computational DTI Template for Aging Studies

Hui Zhang1, Paul Yushkevich1, Daniel Rueckert2, James Gee1

1University of Pennsylvania, Philadelphia, PA, USA; 2Imperial College London, London, UK

We report the development of a population-specific DTI template for study aging. Our template is constructed using the freely available imaging data from the IXI brain database, with the software package DTI-TK. The template has been developed to support the recently proposed tracted-specific white matter analysis by Yushkevich et al.

14:30         3232.     Template Selection for FMRI Studies of Elderly Subjects

Minjie Wu1,2, Lei K. Sheu1, Carmen Andreescu1, James T. Becker1, Costin Tanase3, Howard J. Aizenstein1,2

1Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA; 2Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; 3Magnetic Resonance Research Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

In this study we have compared performance of 3 templates (Colin27, ICBM152, and an elderly template) in terms of co-localization of fMRI signal in elderly individuals on a finger-tapping task. The maximum t-values, location, and size of the regions were similar for all 3 templates. When we looked specifically at elderly subjects with the most prominent ventricles, we found there was a greater peak and smaller extent for the most medial motor cortex regions, but not in the most lateral motor cortex, which suggests the elderly template may be most beneficial for co-localization in medial structures due to their proximity to the ventricles.

15:00         3233.     Radial Diffusivity Template of Corpus Callosum. Correlation with Normal Aging.

Fabrizio Fasano1,2, Mara Cercignani1, Barbara Basile1, Carlo Caltagirone3,4, Marco Bozzali1

1Neuroimaging Laboratory, Fondazione Santa Lucia, Roma, Italy; 2Siemens Medical , Milano, Italy; 3Clinical and Behavioural Neurology Laboratory, Fondazione Santa Lucia, Roma, Italy; 4Department of Neurological Sciences, University of Rome Tor Vergata, Roma, Italy

We computed the radial diffusivity map on the corpus callosum of 35 healthy subjects ranging 20-80 years. A mid-sagittal template of corpus callosum was obtained by co-registeri all mid-sagittal slices in a semi automated non linear fashion. Statistical analysis was performed on the data to asses for correlation between radial diffusivity values and the normal aging process in a voxel based approach.

 
Exhibit Hall 2-3                    Wednesday 13:30-15:30          Computer 8

13:30         3234.     Interrelationships of Brain Microstructural and Macrostructural Abnormalities in the Oldest Old.

Vijay K Venkatraman1,2, Howard Jay Aizenstein1,3, Anne Barbara Newman2,4, Caterina Rosano2,4

1Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; 2Center for Aging and Population Health, University of Pittsburgh, Pittsburgh, PA, USA; 3Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA; 4Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA

Diffusion Tensor Imaging and Magnetization Transfer imaging have been recently used in geriatric neuroepidemiology to uncover the presence of microstructural brain abnormalities that would otherwise remain hidden with conventional MRI sequences and markers. However, the relationships between micro- and macro- structural abnormalities have not been examined in the oldest old. Understanding these relationships is useful to improve measurements of subtle brain changes with aging and to understand the mechanisms underlying responses to treatment and brain plasticity in older adults.

14:00         3235.     Tract Based Spatial Statistics Reveals Longitudinal White Matter Changes in Normal Ageing

Thomas Richard Barrick1, Rebecca Anne Charlton1, Christopher Alan Clark2, Hugh Stephen Markus1

1Centre for Clinical Neuroscience, Saint George's, University of London, London, UK; 2Institute of Child Health, University College London, London, UK

Recently there has been increased interest in the role of white matter in normal aging, but little research has investigated age-related change in DTI parameters. Using tract based spatial statistics (TBSS) we assessed white matter structural integrity change in a group of 74 healthy middle aged and elderly adults over two-years. Results showed significant increases in MD throughout the whole brain. Significant decreases in FA were less widespread but still present throughout the brain. In particular, we found no evidence that there was a greater rate of change in the anterior frontal regions contrary to the frontal ageing hypothesis.

14:30         3236.     Tract-Specific White Matter Integrity and Cognitive Ability in Youth and Old Age

Susana Muñoz Maniega1, Lars Penke1, Jonathan D. Clayden2, Catherine Murray1, Mark E. Bastin1, Alan J. Gow1, Joanna M. Wardlaw1, Ian J. Deary1

1University of Edinburgh, Edinburgh, UK; 2Institute of Child Health, University College London, London, UK

The aim of this work is to understand how brain white matter integrity contributes to age-related cognitive decline in humans. Tractography was performed in a group of healthy older people who undertook full cognitive testing at age 70. Results from IQ testing at age 11 of the same individual was also available. Tract-averaged FA and MD were calculated and related with these cognitive measures. Uncinate fasciculus showed correlations with IQ at both age 11 and 70 and arcuate fasciculus measures correlated with mental speed at age 70. These findings support recent hypotheses for the neural basis for intelligence.

15:00         3237.     Gender and Age Dependence of Cingulum and Corpus Callosum in Healthy Volunteers Assessed by Diffusion Tensor Imaging: A Virtual Dissection Study

Hanna Järnum1, A.- M. Stausholm1, Elena G. Steffensen2, Carsten Wiberg Simonsen1, Søren Lundbye-Christensen3, Tina Obel3, Ernst Torben Fründ1,4, E-M. Larsson1

1Department of Radiology, Aalborg Hospital/Århus University Hospital, Aalborg, Denmark; 2Department of Radiology, Aalborg Hospital/Århus University Hospital, Aalborg , Denmark; 3Center for Cardiovascular Research, Aalborg Hospital/Århus University Hospital, Aalborg, Denmark; 4GE Healthcare - Applied Science Laboratoy Europe

Purpose: To perform virtual dissections of the limbic tract cingulum comparing with corpus callosum in healthy volunteers.

 
Exhibit Hall 2-3                    Thursday 13:30-15:30          Computer 8

13:30         3238.     13C MRS During [3-13C]lactate Infusion Under Hyperinsulinemic-Hypoglycemic Conditions Reveals Compartmentalized Lactate Metabolism in Human Brain

Henk De Feyter1, Kitt Falk Petersen2, Graeme F. Mason3, Gerard Sanacora4, John Krystal4, Barbara Gulanski5, Robert S. Sherwin5, Kevin L. Behar4, Robin A. de Graaf1, Fawzi Boumezbeur6, Gerald I. Shulman2, Douglas L. Rothman1

1Diagnostic Radiology, Yale University, New Haven, CT, USA; 2Internal Medicine, Yale University, New Haven, CT, USA; 3Psychiatry, Yale University, New Haven, CT, USA; 4Department of Psychiatry, Yale University, New Haven, CT, USA; 5Department of Internal Medicine and Endocrinology, Yale University, New Haven, CT, USA; 6Neurospin, Gif-sur-Yvette, France

The brain relies on glucose as its primary energy substrate but is also able to use alternative substrates to fuel its metabolism. We present preliminary results from 13C MRS studies during [3-13C]lactate, [1-13C]glucose and [2-13C]acetate infusion to determine relative neuronal and glial consumption of blood lactate versus blood glucose. Infusion of [3-13C]lactate during hyperinsulinemic hypoglycemia to inhibit liver gluconeogenesis resulted in significant labeling of brain metabolites. In addition, simplified two-compartment metabolic modeling and comparison of the labeling patterns of brain metabolites during [1-13C]glucose and [2- 13C]acetate infusion indicate that lactate is metabolized primarily in the neuronal compartment with a similar ratio of neuronal to glial consumption as glucose.

14:00         3239.     Regional Age-Related Changes in the Monkey Brain Measured with Proton Magnetic Resonance Spectroscopy

Xiaoying Fan1, Stephen Schettler1, Sahil Jain1, Donna Murray1, Dae-Shik Kim1, Douglas Rosene1, Ron Killiany1, Itamar Ronen1

1Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, USA

Proton MRS together with tissue volumetric information from high resolution MRI images were employed to carefully assess regional concentrations of brain metabolites in a tightly controlled population of rhesus monkeys

14:30         3240.     Quantitative Relaxographic Assessment of Age Related Changes in Non-Human Primate Brain

Jeffrey Moses Njus1, James R. Pollaro1, Mathew T. Snodgrass1, Vincent B. Warren2, Ethan Muldoon1, John Cunneen1, Steven G. Kohama2, William D. Rooney1

1Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, USA; 2Oregon National Primate Research Center, Beaverton, OR, USA

MRI T1 mapping offers a precise way to characterize brain tissue in vivo and has potential for fast objective evaluation of physical and morphological properties. The purpose of this study was to evaluate age-related changes in the non-human primate (NHP) brain from infant to middle age. To accomplish this goal, full brain 1H2O T1 relaxographic data sets were collected from 53 healthy Japanese macaques (21M, 31F, 1H) at 3 T. T1 histograms were constructed and analyzed to determine the normalized volume fractions of white matter (WM), gray matter (GM), CSF tissue water, and average T1 values for WM and GM. WM and GM T1 values decreased significantly with age in the developing NHP brain.

15:00         3241.     T2 Relaxation Time Is Decreased in Hippocampus of Aged Rats: Analysis of the Effect of the Peroxisome Proliferator-Activated Receptor γ Agonist Rosiglitazone

Christoph Blau1, Ranya Bechara1, Christian Matthias Kerskens1, Marina Anne Lynch1

1Trinity College Institute of Neuroscience, Dublin, Ireland

We show an age-dependent decrease in T2 relaxation times in the cortex and hippocampus of the rat brain as measured by fast imaging with steady-state precession (FISP) and echo-train multi-slice multi-echo (MSME) at 7 Tesla, which is absent in mixed- and white matter areas. We show an increase in T2 relaxation time in the hippocampus of aged rats chronically treated with the selective ligand of peroxisome proliferator-activated receptor γ Rosiglitazone compared to age-matched controls. The change in T2 is hypothesised to be due to age-related neuroinflammation that is being partially inhibited by the drug.

 


 
Multiple Sclerosis
Exhibit Hall 2-3                    Monday 14:00-16:00          Computer 9

14:00         3242.     Optimisation of T2* Imaging for the Investigation of White-Matter MS Lesion Heterogeneity

Jennifer Elizabeth Dixon1, Matthew J. Brookes1, Paul S. Morgan2,3, Ali M. Al-Radaideh1, Emma C. Tallantyre4, Nikos Evangelou4, Peter G. Morris1

1Sir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, Nottingham, Nottinghamshire, UK; 2Radiology & Radiological Science, Medical University of South Carolina, Charleston, SC, USA; 3Academic Radiology, University of Nottingham, Nottingham, Nottinghamshire, UK; 4Department of Clinical Neurology, University of Nottingham, Nottingham, Nottinghamshire, UK

T2*-weighted imaging at 7T has been suggested as a technique for the in vivo study of the spatial relationship between MS lesions and parenchymal blood vessels. In order to obtain an accurate picture of this relationship it is essential to determine and implement optimum scanning parameters for the detection of these vessels, as well as to ascertain the minimum size of a vessel that can be detected. We simulate the susceptibility effect around a vessel and predict optimum echo times for magnitude T2*-weighted and susceptibility-weighted images at both 3 and 7T, and show the increase in sensitivity available at 7T.

14:30         3243.     Regional Assessment of WM and GM Damage in Patients with Early MS: A VBM and TBSS Investigation

Eytan Raz1, Mara Cercignani2, Emilia Sbardella1, Porzia Totaro1,3, Carlo Pozzilli1, Marco Bozzali2, Patrizia Pantano1

1Department of Neurological Sciences, Sapienza University, Rome, Italy; 2Neuroimaging Laboratory, Fondazione Santa Lucia - IRCCS, Rome, Italy; 3Istituto di Neuroscienze - NCL, Rome, Italy

Diffuse MRI abnormalities have been largely described in multiple sclerosis (MS) at the earliest stages, involving both white (WM) and grey matter (GM). However, the relationship between WM and GM damage is not fully understood. We recruited 34 patients presenting with symptoms suggestive of a first episode of MS. SPM5 and FSL were respectively used for VBM (GM) and TBSS (WM) analyses. We found a diffuse WM damage in early MS and CIS, which involves most of the WM tracts. No significant changes were observable when considering regional GM volumes. This suggests that WM damage is most relevant in determining the early steps of brain damage in MS.

15:00         3244.     Relating Thalamic Atrophy and White Matter Lesions at the Earliest Stages of Multiple Sclerosis

Bagrat Amirbekian1, Mason Shieh1, SungWon Chung1, Darin T. Okuda2, Daniel Pelletier2, Roland G. Henry1,3

1Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA; 2Neurology, University of California, San Francisco, CA, USA; 3Graduate Group in Bioengineering, University of California, Berkeley & San Francisco, CA, USA

A previous VBM study has shown thalamic atrophy significantly correlated with white matter lesion volume in CIS patients at presentation. One possibility is that WM lesions and thalamic atrophy are both due to a common disease mechanism and therefore do not have a causative relation. Alternatively, the white matter lesions may cause the thalamic atrophy and/or thalamic degeneration may be in part responsible for pathology arising in connected axonal bundles. In order to shed further light on these possibilities, we have investigated this relationship using diffusion tensor MRI fiber tractography to delineate the white matter pathways connected to the thalamus.

15:30         3245.     Impairment of Emotional Processing in Multiple Sclerosis: An Event-Related FMRI Study

Barbara Basile1, Ugo Nocentini2, Giovanna Comanducci2, Rosalba Mannu2, Carlo Caltagirone3,4, Marco Bozzali3

1Neuroimaging Laboratory , Santa Lucia Foundation, Rome, Italy; 2Department of Clinical and Behavioural Neurology, Santa Lucia Foundation, Rome, Italy; 3Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy; 4Department of Neuroscience, University Tor Vergata, Rome, Italy

Patients with multiple sclerosis (MS) exhibit significantly higher rates of anger, depression and pathological laughing and crying. The aim of this study was to investigate, through a functional MRI, emotional processing in MS patients. Results demonstrate how MS patients show significantly abnormal brain activation, compared to controls in both negative emotional states and joy. Higher brain activation was observed in anger and sadness conditions in MS patients, compared to controls, while the opposite effect was observed in joy condition. These abnormalities might reflect the underlying brain tissue damage.

 
Exhibit Hall 2-3                    Tuesday 13:30-15:30          Computer 9

13:30         3246.     Serial MRI in Epidemiology: Seasonal Occurrence of New MS Lesions

Dominik S. Meier1, Charles R.G. Guttmann1

1Radiology, Brigham & Women's Hospital - Harvard Medical School, Boston, MA, USA

The use of serial MRI for studies of epidemiological scope is explored on the example of measuring seasonal variation of multiple sclerosis (MS) disease activity. A seasonality of MS disease activity is suggested from clinical and immunological variables, but MRI findings thus far remain controversial. New T2 lesion occurrence and contrast-enhancing lesions (CEL) were measured over a one-year period. We observed greater activity/likelihood in spring and summer for new T2 lesions but not CEL. CEL have a brief window of visibility and thus are sensitive to observation bias. The use of new T2 lesions in lieu of CEL holds considerable advantages and should be seriously considered in its application to clinical trials.

14:00         3247.     Morphogenesis of Cerebral Cortex in Healthy Aging and Multiple Sclerosis: Potential Marker of Early White Matter Injury.

Martin Kavec1, Mathieu Vokaer2, Danielle Balériaux1

1Neuroradiology, Erasme Hospital, Brussels, Belgium; 2Neurology, Erasme Hospital, Brussels, Belgium

The present data suggest that along the healthy aging, large areas of associative cortices may lose shape and compactness. These changes take place predominately in the left hemisphere. In the MS subjects on the other hand, the local gyrification index increased with disability in a several areas of associative cortices. These areas were larger and distinct from those suffering from MS related cortical atrophy. Therefore, local gyrification index may possibly probe for processes of an early irreversible axonal damage, and thus bring more insight into pathology of MS.

14:30         3248.     Normal-Appearing White Matter Quantitative Magnetization Transfer Imaging Correlates with Disability  in Multiple Sclerosis

Barbara Basile1,2, Mara Cercignani3, Fabrizio Fasano3, Ugo Nocentini4, Carlo Caltagirone4,5, Marco Bozzali3

1Neuroimaging Laboratory , Santa Lucia Foundation, Rome, Italy, Italy; 2School of Cognitive Psychotherapy, Rome, Italy, Italy; 3Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy, Italy; 4Department of Clinical and Behavioural Neurology, Santa Lucia Foundation, Rome, Italy, Italy; 5Department of Neuroscience, University Tor Vergata, Rome, Italy, Italy

Quantitative magnetization transfer (qMT) probes the MR properties of protons in macromolecules such as myelin. A clinically feasible whole-brain qMT protocol was implemented in order to investigate the different pathological substrates of normal appearing white matter (NAWM) and lesions in Multiple Sclerosis (MS), and to assess whether qMT parameters may explain MS patients clinical disability. Results showed significant differences across healthy and damaged tissues in qMT values. Consistently with our predictions, clinical disability was explained by specific qMTIparameters in both NAWM and lesions.

15:00         3249.     Preservation of Brain Adaptive Properties Contributes to the Clinical Picture of Benign Multiple Sclerosis

Maria Assunta Rocca1,2, Antonia Ceccarelli1, Sebastiano Galantucci1,2, Angelo Ghezzi3, Elisabetta Pagani1, Andrea Falini4,5, Giancarlo Comi2, Massimo Filippi1,2

1Neuroimaging Research Unit, Scientific Institute Hospital San Raffaele, Milan, Italy; 2Department of Neurology, Scientific Institute Hospital San Raffaele, Milan, Italy; 3MS center, Ospedale di Gallarate, Gallarate, Italy; 4CERMAC, Scientific Institute Hospital San Raffaele, Milan, Italy; 5Department of Neuroradiology, Scientific Institute Hospital San Raffaele, Milan, Italy

To investigate the mechanisms responsible for the favorable clinical course of benign multiple sclerosis (BMS), we acquired functional magnetic resonance imaging (fMRI) during right hand movement in 17 BMS, 15 secondary progressive (SP) MS patients and 10 healthy volunteers. While, compared to controls, BMS patients had exclusively an increased activation of the left primary sensorimotor cortex, SPMS patients had, compared to the other two groups, increased activations of several areas in the fronto-parietal lobes, and reduced activations of the supplementary motor area, basal ganglia, and cerebellum, suggesting a relative preservation of brain adaptive properties in BMS.

 
Exhibit Hall 2-3                    Wednesday 13:30-15:30          Computer 9

13:30         3250.     Fiber-Tracking Through Multiple Sclerosis Lesions Using Probabilistic Tracking

Alexander B. Pine1, Stephen Jones2, Mark Lowe2, Ken Sakaie3, Micheal Philips2

1Cleveland Clinic Lerner College of Medicine, Cleveland , OH, USA; 2Radiology, Cleveland Clinic Foundation, Cleveland, OH, USA; 3Department of Radiology, Cleveland Clinic Foundation, Cleveland, OH, USA

Deterministic fiber-tracking methods are poorly suited to track through regions of low anisotropy such as MS lesions. In contrast, probabilistic tracking, when combined with non-tensor fiber orientation distribution estimation methods, can avoid such pitfalls. It is hypothesized that methods utilizing probabilistic tracking are capable of propagating tracks through such isotropic anomalies as MS lesions. This study specifically aimed to validate probabilistic tracking as a reliable tool that allows fiber tracing to propagate through MS lesions. Additionally, driven by the overall goal to characterize white matter integrity in MS patients, this work has begun applying this method to quantitatively evaluate diffusion parameters of fiber tracks that traverse MS lesions.

14:00         3251.     Contrast Simulation and Measurement in the Optic Nerve at 3T

Lauren Wallis1, LiSze Chow1, Martyn NJ Paley1, Hardeep Singh Mudhar2, Simon Hickman3, Nigel Hoggard1

1Academic Radiology, University of Sheffield, Sheffield, Yorkshire, UK; 2Histopathology, STH NHS Trust, Sheffield, Yorkshire, UK; 3Neurology, University of Sheffield, Sheffield, Yorkshire, UK

It is often assumed by radiologists in MR studies that the optic nerve is surrounded by a 2mm cylinder of CSF. Investigation of anatomy and contrast studies using a range of inversion times suggest the optic nerve has 3 main compartments with shorter T1 than CSF. CSF is only a small faction of the overall nerve bundle. Simulations using a three compartment model agree with in vivo measurements at 3T.

14:30         3252.     Structural Differences in OCB-/+ Patients with Clinically Isolated Syndrome Suggestive of MS

Yasheng Chen1, Valerie Jewells1, Danielle Speer2, Taylor Stone1, Silva Markovic-Plese2, Hongyu An1, Hongtu Zhu3, Dinggang Shen1, Weili Lin1

1Radiology, UNC-CH, Chapel Hill, NC, USA; 2Neurology, UNC-CH, Chapel Hill, NC, USA; 3Biostatistics, UNC-CH, Chapel Hill, NC, USA

This work is aimed to detect brain structural differences between patients of clinically isolated syndrome (CIS) suggestive of multiple sclerosis with and without the presentation of Oligoclonal bands (OCB) in CSF. With both diffusion tensor imaging and T1 based tissue density map, we found that OCB+ patients have significantly abnormal DTI parameters and white matter tissue density loss in both corpus callosum and frontal white matter. Our findings suggest that OCB+ may have a worse brain abnormality than OCB- patients at their initial clinical presentation.

15:00         3253.     MRI Features of the Inflamed Spine: A Comprehensive Comparison of Spinal Lesions in Acute Transverse Myelitis and Multiple Sclerosis in Children

Helen Branson1,2, Monica Makhijma2, Manohar Shroff2,3, Sandra Magalhaes2, Leonard H. Verhey4, Brenda Banwell2

1The University of Toronto, Toronto, Ontario, Canada; 2The Hospital for Sick Children, Canada; 3The University of Toronto, Canada; 4Neurosciences & Mental Health, The Hospital for Sick Children, Toronto, ON, Canada

MRI characteristics of spinal cord lesions in children with multiple sclerosis (MS) and how they differ from those of children with acute transverse myelitis (ATM) have not been well-studied. Using a standardized MRI scoring tool, we compared spinal cord lesions in children with clinically-definite MS to children with monophasic ATM. We found that, compared to MS patients, children with ATM have longer lesions and are more likely to be found in anterior and central spinal cord regions. In contrast, children with MS were more likely to have lesions in the posterior aspect of cervical and thoracic regions.

 
Exhibit Hall 2-3                    Thursday 13:30-15:30    &n bsp;  &nbsSyr 9

13:30         3254.     Atrophy and Shape Changes in Deep Gray Matter in Multiple Sclerosis: A Tensor Based Morphometry

Guozhi Tao1, Sushmita Datta1, Renjie He1, Ponnada A. Narayana1

1Department of Diagnostic and Interventional Imaging, University of Texas, Medical School at Houston, Houston, TX, USA

Tensor based morphometry was applied to determine the atrophy and shape changes in deep gray matter (DGM) structures in 88 relapsing remitting multiple sclerosis (RRMS) patients. Statistical analysis demonstrates significant atrophy and shape change in several DGM structures. The atrophy and/or shape change of various DGM structures, particularly thalamus, putamen, and caudate nucleus were found to be significantly correlated with expanded disability status score (EDSS).

14:00         3255.     Apparent Anisotropy in a LES Model of Demyelination Observed by QSI: Effect of Experimental Parameters

Debbie Anaby1, Ian D. Duncan2, Yoram Cohen1

1School of Chemistry, Tel Aviv University, Tel Aviv, Israel; 2Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA

The contribution of myelin to water diffusion anisotropy measurements in neuronal tissue is not yet totally clear. Therefore, both low and high b-value q-space diffusion MRI (QSI) were used to study the diffusion characteristics of long evans shaker (LES) rats spinal cord (demyelination model). QSI was measured both parallel and perpendicular to the long axis of the spinal cord at different diffusion times. We found reduced FA in LES spinal cord as compared to controls for all diffusion times. Clearly, the significant difference between FA values of the two groups increased with the increasing diffusion times and diffusion weighting.

14:30         3256.     Sequential Monitoring of Fractional Anisotropy (FA) and Apparent Diffusion Coefficient (ADC) in an Experimental Model of Demyelination by DTI and DWI

Krithika Balasubramanian1, Uma Sharma1, S Senthil Kumaran1, S Muthuraj2, Dipti N. Prasad2, Naranamangalam R. Jagannathan1

1Department of NMR and MRI Facility, All India Institute of Medcial Sciences, New Delhi, Delhi, India; 2Department of Neurobiology, Defence Institute of Physiology & Allied Sciences, Delhi, India

A sequential study of the changes in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in an LPC induced demyelinating rat model (internal capsule area of rat brain) at various stages of de- and re-myelination was carried out at 4.7 T. Results show that as demyelination progresses, there is an increase in ADC and a decrease in FA indicating damage to the myelin surrounding nerve fibers. Subsequently, these values reach near normal values during remyelination process. The study improved our understanding of the pathophysiology of the de- and re-myelination process.

 


 
MRA & Flow of Neurovascular Disease
Exhibit Hall 2-3                    Monday 14:00-16:00          Computer 10

14:00         3257.     Hybrid HYPR MRA

Yijing Wu1, Steven R. Kecskemeti1, Patrick Turski2, Charles A. Mistretta3

1Medical Physics, University of Wisconsin, Madison, Madison, WI, USA; 2Radiology, University of Wisconsin, Madison, Madison, WI, USA; 3Medical Physics and Radiology, University of Wisconsin, Madison, Madison, WI, USA

HYPR FLOW was able to provide 0.69 mm isotropic (.33mm3) spatial resolution with 0.5s frame rate and a 0.75s temporal window for contrast-enhanced information. Although this approach has good resolution and provides flow information and flow derived quantities, it is difficult to reduce voxel volume below about 0.3 mm3 due to the need to acquire four excitations per projection. We present here early results using an alternate hybrid HYPR MRA technique called HYPR TOF in which a separately acquired TOF examination is used to provide a composite image for processing time resolved CE MRA data. Although initially implemented in a stack of stars geometry, this approach when combined with VIPR acquisition will permit greater spatial resolution than HYPR FLOW at the expense of physiological information. This will be important for some aneurysm cases where higher spatial resolution is desirable.

14:30         3258.     Non-Contrast Enhanced Three-Dimensional MR Digital Subtraction Angiography at a Temporal Resolution of 100 Msec.

Masaaki Hori1,2, Nobuyuki Shiraga2, Yasushi Watanabe3, Shigeki Aoki4, Sachiko Isono5, Masao Yui6, Tsutomu Araki1

1University of Yamanashi, Chuou, Yamanashi, Japan; 2Radiology, Toho University Omori Medical Center, Ota, Tokyo, Japan; 3University of Tokyo, Japan; 4Radiology, School of Medicine, Juntendo University, Japan; 5Toshiba Medical Systems, Japan; 6MRI Development dept, Toshiba Medical Systems, Japan

Purpose of this study is to estimate the value of Time-Spatial Labeling Inversion Pulse (Time-SLIP) magnetic resonance digital subtraction angiography (MRDSA) in evaluation of intracranial arteries at 1.5T for clinical use. As results, time-resolved 3D MRDSA without contrast material were clearly visualized the branches of the cranial arteries (P<0.01), compared with 3D TOF-MRA. Moreover, MRA containing hemodynamic information from only selected internal carotid artery was able to be obtained. Time-SLIP 3D MRDSA provides hemodynamic information of the circle of Willis, and it may play an important role in assessing cranial arteries in clinical use.

15:00         3259.     Non-Contrast-Enhanced 4D Intracranial MR Angiography with 4D NATIVE TrueFISP

Xiaoming Bi1, Peter Weale1, Peter Schmitt2, Sven Zuehlsdorff1, Renate Jerecic1

1Siemens Medical Solutions USA, Inc., Chicago, IL, USA; 2Siemens AG Healthcare Sector, Erlangen, Germany

Contrast-enhanced, time-resolved three-dimensional (4D) MRA has been widely used to exam the anatomical and dynamic flow information of vasculature. Typically temporal and spatial resolutions have to be traded in order to synchronize data acquisition to the short first pass of contrast agent. In this work, a non-contrast-enhanced MRA sequence was implemented. The constraints from contrast kinetics as in conventional approaches were eliminated. Extremely high temporal (51.4 msec) and spatial (1.25x1.25x1.25 mm3) resolutions were simultaneously achieved without trading again each other. The feasibility of using such non-contrast-enhanced 4D technique for intracranial MRA was validated from consecutive volunteer studies.

15:30         3260.     Effects of Translation and Pulsation on 3D Contrast-Enhanced MRA of the Carotid Arteries

Dean Thomas Jeffery1,2, Derek J. Emery3, Alan H. Wilman2

1Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada; 2Biomedical Engineering, University of Alberta, Edmonton, AB, Canada; 3Radiology and Diagnostic Imaging, University of Alberta, Edmonton, AB, Canada

3D Contrast Enhanced Magnetic Resonance Angiography (3D CE-MRA) of the carotid arteries may be limited by vessel movement due to the long acquisition times and lack of cardiac gating. Vessel movement, via pulsation and translation, was quantified from cardiac-gated time-resolved images in seven patients with suspected carotid artery disease and then compared with image sharpness in the concurrent 3D CE MRA exam of each patient. Results from 14 arteries in patients indicate that vessel movement during the cardiac cycle does not play a significant role in 3D CE-MRA image sharpness.

 
Exhibit Hall 2-3                    Tuesday 13:30-15:30          Computer 10

13:30         3261.     4D Radial-Sliding Window MR Angiograpy of Intracranial Arteriovenous Malformations: Correlation with Digital Subtraction Angiography

Christopher Sean Eddleman1, Hyun Jeong2, Michael C. Hurley2, Christopher C. Getch, Guilherme Dabus2, Bernard R. Bendok2, Hunt H. Batjer, Timothy J. Carroll2

1Neurological Surgery, Northwestern University, Chicago, IL, USA; 2Radiology, Northwestern University

While digital subtraction angiography (DSA) of intracranial arteriovenous malformations (iAVMs) allow the capturing of very high temporal resolution hemodynamic images, time-resolved MR angiography is catching up. Using a radial sliding window and mask subtractions, this time-resolved MRA sequence captures iAVMs at 6 frames/sec and at sub-millimeter spatial resolution, approximating DSA. Here we demonstrate the comparison of 4D RS-MRA and DSA images of iAVMs.

14:00         3262.     qCBF: A Comparison of the Accuracy Between the Bookend Technique, Empirical Reference Values and [O15]-H20 PET in Moyamoya Patients

Vishal Parikh1, John Lee2, Wanyong Shin3, Jessy Mouannes1, Avi Snyder2, Colin Derdeyn2,4, Timothy Carroll1,5

1Biomedical Engineering, Northwestern University, Evanston, IL, USA; 2Radiology, Washington University, St. Louis, MO, USA; 3National Institute of Health, Baltimore, MD, USA; 4Neurology, Washington University, St. Louis, MO, USA; 5Radiology, Northwestern University, Chicago, IL, USA

We compared the accuracy of CBF measurements obtained by the “Bookend” Technique and CBF values rescaled to 22mL/100g/min for white matter. The accuracy with respect to [15O]-H2O positron emission tomography (PET) in patients with angiographically confirmed cerebrovascular disease. We found that the bookend approach provided a stronger correlation with the standard of reference PET values.

14:30         3263.     The Potential of MRI and MRA in the Evaluation of Cerebral Vasospasm in a Rat Model of Subarachnoid Hemorrhage

Shashank R. Ramdurg1, Ashish Suri1, Deepak Gupta1, Sujeet Kumar Mewar2, Uma Sharma2, Naranamangalam R. Jagannathan2, Bhavani S. Sharma1

1Department of Neurosurgery, All India Institute of Medcial Sciences, New Delhi, Delhi, India; 2Department of NMR and MRI Facility, All India Institute of Medcial Sciences, New Delhi, Delhi, India

Cerebral vasospasm causes morbidity and mortality following subarachnoid hemorrhage (SAH). It usually occurs 3 to 9 days after SAH. We evaluated the potential of MRI and MRA to study SAH in a rat model. Direct injection of blood in cisterna magna was used as it provides controlled and quantifiable data to study the pathophysiological changes of SAH. Our study showed that the animal model used provides comparison of diameters of the vascular anatomy of normal rats as well as SAH induced rats. In SAH induced rats, there was partial improvement of the diameters of major vessels on second day.

15:00         3264.     Comparision of High Temporal Resolution 2D Time Resolved Blood Bolus Tagging MRA and 3D Time Resolved Contrast Enhanced MRA for the Assessment of Hemodynamics in Patients with Cerebral Arteriovenous Malformations

Marco Essig1, Frederik Giesel2, Julien Dinkel2, Michael Bock3

1Radiologie, DKFZ, Heidelberg, BW, Germany; 2Radiology, DKFZ, Heidelberg, BW, Germany; 3Medical Physics, DKFZ, Heidelberg, BW, Germany

Hemodynamics of cerebral AVMs can be assessed by dynamic non enhanced and enhanced MRA - TWIST with high quality contrast media allows a perfect AVM characterization

 


 
Animal Models of Ischemia: Characterization
Exhibit Hall 2-3                    Wednesday 13:30-15:30          Computer 10 

13:30         3265.     Effects of Administration Routes on Migration and Distribution of Neural Progenitor Cells Transplanted Into Rats with Ischemia

Lian Li1, Quan Jiang1, Gaungliang Ding1, Li Zhang1, Zhenggang Zhang1, Qingjiang Li1, James R. Ewing1, Michael Chopp1,2

1Neurology, Henry Ford Hospital, Detroit, MI, USA; 2Physics, Oakland University, Rochester, MI, USA

The effects of intra-arterial (IA), intracisternal (IC) and intravenous (IV) injection on migration and distribution of transplanted neural progenitor cells into rats with ischemia have been investigated using MRI. IA delivery results in earlier appearance, more uniform distribution and larger numbers of transplanted cells in the target brain than IC or IV delivery. However, high mortality with IA delivery poses a serious issue for protocol optimization. Stroke severity seems to be another important factor that mediates cell migration. Animals with smaller lesions (less than 10% of brain volume) may get fewer transplanted cells into the parenchyma.

14:00         3266.     Neuroprotective Benefit in a Neurorestorative Treatment of Embolic Stroke with EPO in Rats Detected by MRI

Guangliang Ding1, Quan Jiang1, Lian Li1, Li Zhang1, Ying Wang1, Zhenggang Zhang1, Swayamprava Panda1, qingjiang Li1, James R. Ewing1, Michael Chopp1,2

1Neurology, Henry Ford Hospital, Detroit, MI, USA; 2Physics, Oakland University, Rochester, MI, USA

Chronic erythropoietin (EPO) treatment of stroke in rats exhibited both neuroprotective and neurorestorative benefits. Dynamic T2WI images demonstrated that the expansion of ventricle in the ipsilateral hemisphere was restrained in EPO-treated rats. Ventricular volume ratios (ipsilateral vs contralateral) 6 weeks after stroke were 1.99 ± 0.15 for the treated rats and 2.35 ± 0.26 for the controls (p < 0.01). Volume of the cerebral parenchyma decreases when the ventricle expands, which indicates loss of cerebral tissue. Our results demonstrate that chronic EPO treatment of embolic stroke reduced the expansion of ventricular volume that ultimately protects against loss of cerebral tissue.

14:30         3267.     Contrast Agent Leakage to Lateral Ventricle After Transient Cerebral Ischemia

Aysan Durukan1,2, Daniel Strbian1,2, Ivan Marinkovic1,2, Miia Pitkonen2, Eric Pedrono2, Usama Abo-Ramadan1,2, Turgut Tatlisumak1,2

1Neurology, Helsinki University Central Hospital, Helsinki, Finland; 2Biomedicum Helsinki Experimental MRI Laboratory, Helsinki, Finland

Using gadolinium-enhanced MRI, we systematically investigated post-ischemic blood-brain barrier and blood-cerebrospinal fluid barrier integrities, in order to explore whether these two barriers of the rat brain respond similarly to transient ischemic insult. Lateral ventricle on the ischemic hemisphere was enhanced as an early and transient phenomenon occurring most often at 0-12 hours after reperfusion, but never seen after 36 hours. This temporal pattern of lateral ventricle enhancement was clearly different then of parenchymal enhancement, which was continuous up to 5 weeks, suggesting a difference in disruption mechanisms of blood-brain and blood-cerebrospinal fluid barriers of the brain.

15:00         3268.     Alterations of DTI Indices in Bilateral Corticospinal Tract Following Unilateral Stroke in a Rat Model

Deqiang Qiu1, Maurits P.A. van Meer2,3, Pek-Lan Khong1, Rick M. Dijkhuizen2

1Diagnostic Radiology, The University of Hong Kong, Hong Kong, China; 2Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands; 3Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht

A Diffusion Tensor Tractography-based quantification method was used to study changes of DTI indices in the bilateral corticospinal tract (CST) following unilateral stroke in rats. Significant changes in DTI indices were found in ipsi- as well as contralesional CST, which point toward widespread structural alterations. We found that reduced FA and MD were mainly driven by reductions in axial diffusivity (¦Ë//), while radial diffusivity was relatively stable.

 
Exhibit Hall 2-3                    Thursday 13:30-15:30          Computer 10

13:30         3269.     Characterization of Early Hypoxic-Ischemic Injuries to the Neonatal Mouse Cerebral Cortex and Hippocampus Using Diffusion Tensor Imaging

Julie Nogee1, Brian S. Stone2, Devin W. Mack2, Lee J. Martin3, Michael I. Miller4, Susumu Mori5, Frances J. Northington2, Jiangyang Zhang5

1Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Pediatrics, Johns Hopkins University School of Medicine; 3Pathology, Johns Hopkins University School of Medicine; 4Center of Imaging Science, Johns Hopkins University; 5Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

We examined early cortical and hippocampal injury in a neonatal mouse model of hypoxia-ischemia using ex vivo DTI and histology. DTI revealed changes in fractional anisotropy and disruption of the radial structural patterns in the sensory cortex and hippocampal pyramidal cell layer at 24 hours after injury in p8, as well as in p11 and p15 mice. Immunohistochemistry revealed massive neurodegeneration with disruption of the axono-dendritic compartment in the injured cortex and hippocampus at p8, p11 and p15. The results suggest that DTI is useful for detecting specific neuropathology in the gray matter in this model.

14:00         3270.     Simultaneous EEG and MRI in a Rodent Model of Neonatal Hypoxia-Ischemia

Ward Jennekens1,2, Wim M. Otte3, Maurits P.A. van Meer3, Rick M. Dijkhuizen3, Pieter F.F. Wijn1,2

1Medical Physics, Máxima Medical Center, Veldhoven, Netherlands; 2Eindhoven University of Technology, Eindhoven, Netherlands; 3Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands

The aim of this study is to develop protocols for the indication of MRI examinations based on EEG monitoring of neonates at risk of hypoxic-ischemic encephalopathy. A setup has been developed to simultaneously measure MRI and EEG in an experimental neonatal cerebral ischemia model, in order to find a correlation between changes in anatomy (as measured by MRI) and changes in function (as measured by EEG) following a cerebral infarction. With this setup, it was shown possible to follow the anatomical and functional impact of temporary HI-induced damage processes.

14:30         3271.     Characterization of White Matter Reorganization in Neonatal Hypoxic-Ischemic Cerebral Injury Using Diffusion Tensor Imaging

Kevin C. Chan1,2, Pek-Lan Khong3, Ho-fai Lau1,2, Ed X. Wu1,2

1Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong SAR, China; 2Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong SAR, China; 3Department of Diagnostic Radiology, The University of Hong Kong, Hong Kong SAR, China

This study employs in vivo diffusion tensor imaging (DTI) to understand the late changes in white matter (WM) injury and reorganization in the rat brain upon neonatal hypoxic-ischemic cerebral injury. In particular, detailed inspection of the color-encoded fractional anisotropy (FA) map of the principal eigenvector was performed to compare the orientations of the high FA fibers at the perilesional areas with the WM microstructures in the contralateral hemisphere. In addition to the differences in DTI parameters in the microstructures between both hemispheres, results showed that the perilesional areas had similar fiber orientations as the contralateral external capsule in the anterior section of the brain, and as the internal capsule and the fimbria of hippocampus in the posterior section. We demonstrated that DTI can detect the microstructure and orientations of WM fiber changes at the perilesional areas in vivo, and can be used for non-invasive evaluation of HI brain injuries and reorganization.

15:00         3272.     Functional MRI of Visual Responses in the Late Stage of Neonatal Hypoxic-Ischemic Encephalopathy

Kevin C. Chan1,2, Matthew Man Hin Cheung1,2, Ed X. Wu1,2

1Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong SAR, China; 2Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong SAR, China

This study employs blood oxygenation level-dependent functional MRI to evaluate the visual responses in the rat superior colliculi 2 months after neonatal hypoxic-ischemic encephalopathy. Results showed a smaller BOLD signal amplitude increase in the contralateral superior colliculus of the HIE group in the stimulation period than in the normal group upon either side of eye stimulation. Our results constitute the first fMRI report in evaluating the visual responses of the rat superior colliculus upon neonatal HI insults. These can be potentially useful in establishing the links between the changes related to the visual sensory development after neonatal injury.

 


 
Active Stroke Imaging & Followup in Humans & Animal Models
Exhibit Hall 2-3                    Monday 14:00-16:00          Computer 11

14:00         3273.     Relation Between Cerebral Perfusion Territories and Location of Cerebral Infarcts

Jeroen Hendrikse1, Esben Thade Petersen2,3, Amandine Chèze2, Soke Miang Chng2, Narayanaswamy Venketasubramanian2, Xavier Golay2,4

1UMC, Utrecht, Netherlands; 2National Neuroscience Institute, Singapore; 3CFIN, Department of Neuroradiology, Aarhus University Hospital, Denmark; 4Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Singapore

The perfusion territories of the brain feeding arteries are difficult to assess in-vivo and therefore standard cerebral perfusion territory templates are often used to determine the relation between cerebral infarcts and the feeding vasculature. In the present study we compared this infarct classification, using standard templates, with the individualized depiction of cerebral perfusion territories on selective arterial spin labelling MRI. The additional information from the TASL images changed the classification in 11% of the cortical or border zone infarcts (6 out of 56) whereas no territorial changes were observed in lacunar, periventricular, cerebellar and brainstem infarcts.

14:30         3274.     Double Inversion Recovery (DIR) MR Imaging in Detections of Acute Stroke Lesions

Chung-Min Lee1, Geon-Ho Jahng1, Chang Woo Ryu1, Hyun Cheol Kim1, Dal Mo Yang1

1Radiology, East West Neo Medical Center, Kyung Hee University, Seoul, Korea

To evaluate the depiction of brain ischemic stroke by using DIR and to compare the contrast-normal ratio (CNR) of DIR with that of DWI and FLAIR images, fifty-five patients that had symptoms of acute ischemic stroke were enrolled in this study. Regions of interest (ROI) of the infarction area (L) and its contralateral normal (N) brain lesions were drawn and CNR was obtained for DIR, FLAIR, DWI b1000, and DWI b0 images and for ADC map. In result, the CNR value of DIR has the highest. Differences of mean CNR values among imaging protocols except DWI b1000 have statistically significant.

15:00         3275.     Sequential MR Imaging of Early Reperfusion in Acute Ischemic Stroke Patients

Hongyu An1, Andria L. Ford2, Katie Vo3, Jin-Moo Lee2, William J. Powers4, Weili Lin1

1Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 2Neurology, Washington University in St. Louis, St. Louis, MO, USA; 3Radiology, Washington University in St. Louis, St. Louis, MO, USA; 4Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Sequential perfusion imaging was performed to examine the temporal characteristics of early reperfusion in relation to baseline clinical variables. Our results demonstrate the dynamic nature of cerebral perfusion during acute ischemia with the development of reperfusion and new hypoperfusion volumes concurrently. Improvement of NIHSS strongly correlated with net decrease in hypoperfused tissue. No correlation between the volume of reperfused tissue and the onset-to-tPA treatment time if tPA was given within the three-hour therapeutic window. Additionally, large hypoperfused volumes were not accompanied by large volumes of reperfusion, suggesting that large strokes may be less receptive to the benefits of tPA.

15:30         3276.     Acute Normalization of Apparent Diffusion Coefficient Values May Not Reflect Tissue Recovery in Acute Stroke Patients

Hongyu An1, Andria L. Ford2, Katie Vo3, William J. Powers4, Jin-Moo Lee2, Weili Lin1

1Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 2Neurology, Washington University in St. Louis, St. Louis, MO, USA; 3Radiology, Washington University in St. Louis, St. Louis, MO, USA; 4Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Temporal behavior of ADC lesions during hyperacute ischemia and the final fate of these lesions were examined in the presence or absence of reperfusion. ADC increased significantly after reperfusion, while it decreased slightly if reperfusion did not occur. Reversal of ADC abnormality within 3 to 6 hours after stroke does not necessarily reflect a recovery of ischemic tissue. Furthermore, a time lag was observed between the changes of perfusion and the changes of diffusion (both normalization and worsening).

 
Exhibit Hall 2-3                    Tuesday 13:30-15:30          Computer 11

13:30         3277.     More Is Better: Rater Consensus on Lesion Outline in Acute Stroke Improves Predictive Models

Kristjana Yr Jonsdottir1, Leif Østergaard1, Kim Mouridsen1
1Department of Neuroradiology, Aarhus University Hospital, Aarhus, Aarhus C, Denmark

 

Accurate and reliable delineation of the final infarct in acute ischemic stroke is critical as volume or location of the lesion is typically used as surrogate outcome in clinical stroke trials. Here we study the effect of consensus in outlining the final infarct on a FLAIR image among 9 expert neuroradiologists on the performance of models predicting the final infarct using acute MRI. Predictive models are trained and tested using different degrees of consensus. Our results show that the large variability in lesion delineation effects the models substantially. In particular, complete consensus of the 9 raters provides the highest performance and consequently, multiple rating or standardized lesion definitions should be applied.

14:00         3278.     Acute and Follow-Up MCA Infarct Probability Maps in Stroke Patients with MCA Occlusion

Charlotte Rosso1,2, Guillaume Auzias2, Rémi Cuingnet2, Sophie Crozier1, Eric Bardinet2,3, Stéphane Lehéricy2,4, Sylvain Baillet2, Yves Samson1

1Stroke Center, Pitie Salpetriere Hospital, Paris, France; 2Cognitive Neuroscience and Brain Imaging Laboratory, CNRS-UPR 640 LENA, Pitie Salpetrière Hospital, University Pierre and Marie Curie, Paris, France; 3Center for NeuroImaging Research, Pitie Salpetriere Hospital, Paris, France; 4Department of Neuroradiology, Pitié Salpetrière Hospital, University Pierre and Marie Curie, Paris, France

In this work, we used Diffusion-Weighted Images in 53 ischemic stroke patients with occlusion of the middle cerebral artery to generate stereotactic probability maps of infarction at the acute stage and at follow-up. The probability of infarction was higher in the deep MCA territory at follow-up than at the acute stage. Recanalization, which was associated with good outcome in the literature, rescued some parts of the corticospinal tract. The “clinically relevant” penumbra included the deep MCA territory.

14:30         3279.     Evaluation of Three Ischemic Signs and Ischemic Extent by T2*-Weighted 3-Tesla MRI

Masafumi Harada1, Hitoshi Kubo2, Hiromu Nishitani2, Tsuyoshi Matsuda3

1Dept. of Medical Imaging, Univeristy of Tokushima, Tokushima, Japan; 2University of Tokushima, Japan; 3GE Yokogawa Medical Co. Ltd., Tokyo

The observers f consistency for the ischemic signs by increase of deoxyhemoglobin on T2*-WI was evaluated by kappa statistic, and the quantified map of susceptibility effect was compared with T2*-WI and perfusion imaging. The ischemic sings can be used with acceptable consistency as clinical indices of acute ischemia and T2*-WI would be used as a clinical method to evaluate ischemic extent.

15:00         3280.     Assesment of Blood-Brain Barrier Injury Following Acute Intracerebral Hemorrhage by DCE MRI

Didem Bilensoy Aksoy1, Roland Bammer2, Chitra Venkatasubramanian1, Sandeep N. Gupta3, Michael Mlynash1, Christine A. C. Wijman1

1Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA, USA; 2Department of Radiology, Stanford University, Palo Alto, CA, USA; 3Applied Science Laboratory, General Electric Medical Systems, Baltimore, MD, USA

Dynamic contrast-enhanced (DCE) MRI is proposed as a tool to detect blood-brain barrier (BBB) injury in patients with acute intracerebral hemorrhage (ICH). In this study, DCE MRI and a two-compartment pharmacokinetic model are utilized to quantify BBB leakage one week after ICH onset. A significant increase in BBB permeability is observed in the region immediately surrounding the hematoma.

 
Exhibit Hall 2-3                    Wednesday 13:30-15:30          Computer 11

13:30         3281.     Transient Blood-Brain Barrier Disruption and Changes in Brain Electrolytes at the Edge of the Ischemic Core

Victor E. Yushmanov1, Alexander Kharlamov1, Fernando E. Boada2, Stephen C. Jones2,3

1Department of Anesthesiology, Allegheny-Singer Research Institute, Pittsburgh, PA, USA; 2MR Research Center, Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA; 3Departments of Anesthesiology and Neurology, Allegheny-Singer Research Institute, Pittsburgh, PA, USA

In an attempt to pinpoint the earliest blood-brain barrier (BBB) abnormalities associated with vasogenic edema after stroke, Gd-DTPA contrast enhanced MRI and quantitative K+ histochemistry were performed in the rat brain after permanent MCAO. A thin line of Gd-DTPA enhancement occurred in the CSF space at the ventral edge of the ischemic region at 3.6±0.4 h (n=4) and did not occur in the sham craniotomy. These findings represent the earliest indication of BBB breakdown in the pial circulation and ischemic cortex, which correspond to the K+/Na+ imbalances in the ischemic core and might signal the onset of vasogenic edema.

14:00         3282.     The Measurement of Spatially-Dependant Tissue Sodium Concentration Increase in a Rodent MCAO Stroke Model

Friedrich Wetterling1, Sven Junge2, Arno Nauerth2, Oliviero Gobbo3, I. Mhairi Macrai4, Andrew J. Fagan1,5

1School of Physics, Trinity College Dublin, Dublin, Ireland; 2Bruker BioSpin, Ettlingen, Germany; 3Institute of Neuroscience, Trinity College, Dublin, Ireland; 4Glasgow Experimental MRI Centre, University of Glasgow, Glasgow, UK; 5Centre for Advanced Medical Imaging, St. James’s Hospital, Dublin, Ireland

The aim of this study was to accurately quantify changes in the Tissue Sodium Concentration (TSC) in the acute phase of a rodent stroke model with high spatio-temporal resolution (0.38mm3/ 10min) at 7T.

14:30         3283.     MRI of Bilateral Sensorimotor Network Activation by Direct Intracortical Stimulation in Rats After Unilateral Stroke

Maurits Pieter Adriaan van Meer1,2, Kajo van  der Marel1, Willem Maarten Otte1, Jan Willem Berkelbach van der Sprenkel2, Rick Michiel Dijkhuizen1

1Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands; 2Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, Netherlands

Functional MRI is increasingly applied to investigate rearrangement of ipsi- and contralesional functional brain fields during recovery from stroke. However, these studies typically employ a peripheral stimulation paradigm. In this study we applied BOLD and CBV-weighted fMRI during direct intracortical stimulation (DICS) of the contralesional primary motor cortex in rats acutely after stroke in order to assess changes in central functional connectivity. DICS-fMRI enabled detection of activation responses in bilateral functional networks and we found loss of ipsilesional activation and occasional increased excitability in contralesional sensorimotor regions at 24 h after stroke.

15:00         3284.     Infarct Volume Determined by Acute ADC Correlates Neurological Outcome in Stroke Mice

Chia-Wen Chiang1, Tzy-Haw Wu2, Joong H. Kim2, Sheng-Kwei Song2

1Chemistry, Washington University, St. Louis , MO, USA; 2Radiology, Washington University, St. Louis, MO, USA

Apparent diffusion coefficient (ADC) was determined using diffusion tensor imaging on middle cerebral artery occlusion mice. The infarct volume was quantified based on the stroke induced ADC decrease. Both ADC value and ADC-determined infarct volume were evaluated and correlated with the motor function after acute stroke. The results suggested that the ADC determined infarct volume is a better marker of the neurological disability than ADC value of the infarcted cortex.

 


 
Imaging Psychiatric Conditions
Exhibit Hall 2-3                    Thursday 13:30-15:30          Computer 11

13:30         3285.     MRS at 3 Tesla in Brain of Schizophrenic Patients: Elevated Glutamate in Hippocampus Decreases on Therapy

Florian Schubert1, Frank Seifert1, Karolina Leopold2, Michael Krebs2, Ines Haeke2, Juergen Gallinat2, Martin Schaefer2

1Physikalisch-Technische Bundesanstalt, Berlin, Germany; 2Psychiatry, Charite University Medicine

We performed proton MRS in hippocampus (HC) and cingulate of 30 controls and 30 schizophrenics (on neuroleptics), 17 diagnosed as acute and 13 as chronic. Glutamate was quantified with a dedicated method at TE=80ms to test the influence of memantine, an NMDA receptor antagonist, on cortical glutamate. After baseline examination patients received additional therapy with either memantine or placebo in a double blind study design. Follow-up MRS was performed after 6 weeks. Apart from elevated Glu in patients' HC at baseline, HC-Glu significantly dropped in the group of acute schizophrenics during combination therapy, whereas in the chronic group it remained unchanged.

14:00         3286.     Cerebral Perfusion in Patients with Major Depression  - A Pseudo Continuous Arterial Spin Labelling MRI Study

Hanna Järnum1, Elena G. Steffensen2, Linda Knutsson3, Ernst Torben Fründ1,4, Carsten Wiberg Simonsen1, Ib Scheel Thomsen5, Ajit Shankaranarayanan6, David C. Alsop7, Finn Taagehøj Jensen1, Povl Munk Jørgensen5, E-M. Larsson1

1Department of Radiology, Aalborg Hospital/Århus University Hospital, Aalborg, Denmark; 2Department of Radiology, Aalborg Hospital/Århus University Hospital, Aalborg , Denmark; 3Deaprtment of Medical Radiation Physics,, Lund University Hospital, Sweden; 4GE Healthcare - Applied Science Laboratory Europe; 5Aalborg Psychiatric Hospital/Århus University Hospital, Aalborg, Denmark; 6GE Healthcare, USA; 7Beth Israel Deaconess Medical Center and Harvard Medical School, USA

Purpose: To evaluate cerebral perfusion in patients with major depression.

14:30         3287.     Elevated Lactate Levels and Impaired Neural Circuit in Manic Bipolar Disorder I

Wen-Jang Chu1, Matthew M. Norris2, Jing-Huei Lee1,2, Kelly B. Jarvis1, Xin Wang2, Mi-Jung Kim1, Melissa P. DelBello1, Stephen M. Strakowski1,2, Caleb Adler1

1Psychiatry, University of Cincinnati, Cincinnati, OH, USA; 2Biomedical Engineering, University of Cincinnati, Cincinnati, OH, USA

Abnormal lactate (Lac) levels in patients with bipolar disorder have been identified but difficult to identify. The present study investigated the Lac levels and its distribution in bipolar and healthy brains using 2-D 1H MRSI on a 4 Tesla MR system. The results showed Lac/NAA ratios were significantly higher in bipolar patients compared with healthy subjects. Also, Lac signals were mainly found in patients’ caudate and anterior cingulate cortex, components of the frontal-subcortical network, suggesting that affective dysregulation may be related to the metabolic abnormalities in this impaired neural circuit.

15:00         3288.     Effects of Cortisol on Brain Metabolism: A H-1 Magnetic Resonance Spectroscopy Study at 3.0T

Michael Scheel1, Andreas Stroehle1, Harald Bruhn2

1Clinic for Psychiatry and Psychotherapy, Charite - University Medicine, Berlin, Germany; 2Department of Radiology, Charité - Humboldt University Medical School, Berlin, Germany

A magnetic resonance spectroscopy study at 3 Tesla investigating the effects of cortisol on the concentration of neuronal metabolites. In a two-phase placebo controlled crossover design 21 healthy volunteers have been studied before and after a 4-day intake of 160 mg hydrocortisol or placebo. No evidence for changes due to the corticosteroid intake could be found. These results question some previous results on the same topic.

 


 
Advanced High Field MRS Applications in Animal Models
Exhibit Hall 2-3                    Monday 14:00-16:00          Computer 12

14:00         3289.     Hippocampal Alterations in Congenital Learned Helpless Rats After Electroconvulsive Seizures Detected with in Vivo 1H MR-Spectroscopy at 9.4T

Sarah Biedermann1, Sascha Sartorius1, Lei Zheng1,2, Barbara Vollmayr3, Peter Gass3, Gabriele Ende4, Wolfgang Weber-Fahr1

1RG Translational Imaging, Central Institute of Mental Health, Mannheim, Germany; 2Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany; 3RG Research Group Behavioral Biology, Central Institute of Mental Health, Mannheim, Germany; 4Department Neuroimaging, Central Institute of Mental Health, Mannheim, Germany

Psychiatric patients suffer from the time-delayed onset of antidepressive treatments. Electroconvulsive treatment (ECT) has a more rapid acting onset of the antidepressive effect. With the help of high field 1H magnetic resonance spectroscopy at 9.4 T we examined congenital learned helpless (cLH) rats’ hippocampi after a six days course of ECS. We found a significant increase in choline, glutamate and GABA concentrations after ECS. The increase of glutamate correlated significantly with an increase of GABA. Glutamine was unaltered by ECS. These results support the hypothesis of ECS induced neurogenesis and increased synaptic plasticity.

14:30         3290.     Direct and Noninvasive Measurement of Cerebral Metabolic Rate of ATP in Cat Brain and Its Physiological Implications

Xiao-Hong Zhu1, Yi Zhang1, Kamil Ugurbil1, Wei Chen1

1CMRR, Department of Radiology, University of Minnesota Medical School, Minneapolis, MN, USA

Adenosine triphosphate (ATP) metabolism provides energy at cellular level for all living species. In the brain, majority of ATP is formed in mitochondria through oxidative phosphorylation and utilized in cytosol for supporting normal brain function. By applying the in vivo 31P MRS in combine with the magnetization transfer (MT) approach, we are able to directly and non-invasively measure the cerebral metabolic rate of ATP (CMRATP) in cat brain at 9.4T. The results of the CMRATP measurement have been validated via: i) using different MT techniques; and ii) comparing with the estimated CMRATP derived from the CMRO2 previously obtained from the same cat model. In addition, by correlating the experimentally determined CMRATP with the CMRO2 values in cat, as well as in rat and human brain, we could obtain the P:O ratios in these species, which indicate that oxidative phosphorylation indeed dominates the ATP production in these resting brains.

15:00         3291.     Metabolic Profiles in the Brain of a Transgenic Mouse Model of Type 2 Diabetes Assessed Using in Vivo 1H MRS at 9.4 T

Wen-Tung Wang1, Bhumsoo Kim2, Eva Feldman2, In-Young Choi1,3

1Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, USA; 2Department of Neurology, University of Michigan, Ann Arbor, MI, USA; 3Department of Neurology, Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA

Alterations in cerebral metabolism and function have been suggested in type 2 diabetes, particularly in aging. To characterize metabolic abnormalities in the brains with type 2 diabetes, a rodent model for type 2 diabetes (dbdb) was studied in hippocampus and striatum using localized ultra-short echo time 1H MRS. Brain glucose levels were over twofold higher in diabetic mouse, As compared with those in control mice. The dbdb mice also showed significant increases in the levels of ascorbate, myo-inositol and taurine, suggesting alterations in antioxidant defense and osmoregulation. NAA was lower in the dbdb mice, which may indicate neuronal loss and is consistent with findings in diabetic patients.

15:30         3292.     Glycine Tissue Level in Medulla Oblongata Measured in Vivo with 1H MRS at 9.4 T in Rat Brain

Lijing Xin1, Giulio Gambarota1, João Miguel das Neves Duarte1, Vladimir Mlynarik1, Rolf Gruetter1,2

1Laboratory of functional and metabolic imaging, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland; 2Department of Radiology, University of Lausanne, Lausanne, Switzerland

Medulla oblongata (MO) is the part of the brainstem which regulates autonomic functions, such as heart beat, breathing and blood pressure. In previous studies, high levels of glycine have been reported in vitro in the MO. The present study demonstrated the feasibility of in vivo neurochemical profile quantification of 17 metabolites including glycine in the MO, by localized proton NMR spectroscopy at 9.4T. Compared to hippocampus, striatum and cortex, the MO displayed a three-times higher glycine concentration, as well as a significant decrease in glutamate, glutamine and taurine levels.

 
Exhibit Hall 2-3                    Tuesday 13:30-15:30          Computer 12

13:30         3293.     Towards Structure Specific Quantitative Macromolecular Content of Mouse Brain from Chemical Shift Imaging Data at 11.7 T

Hélène Ratiney1, Michaël Sdika2, Olivier Beuf1, Yann Le Fur2, Sophie Cavassila1

1Université de Lyon, CREATIS-LRMN, CNRS UMR 5220; Inserm U630; INSA-Lyon; Université Lyon 1, Villeurbanne, France; 2CRMBM, CNRS UMR 6612, Marseille, France

The MR spectroscopic macromolecular signal usually considered as a nuisance contribution in the quantification of short echo time signals might reveal some interest as a spectroscopic biomarker by itself. The present work aims at studying the specificity of the macromolecular patterns within the mouse brain structures. A whole MRS coupled to MRI method is proposed going from acquisitions of the macromolecules ,using diffusion weighted spectroscopic imaging and acquisitions of high resolution mouse brain images, to automated mouse brain structure segmentation and  MRS quantification procedure.

 

14:00         3294.     In Vivo MRS Studies of Metabolic Changes Induced by Recurrent Antecedent Hypoglycemia Probed by 3-  13C-Lactate

Lihong Jiang1, Raimund I. Herzog2, Graeme F. Mason, Robin A. de Graaf, Douglas L. Rothman, Robert S. Sherwin2, Kevin L. Behar3

1Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA; 2Internal Medicine, Yale University School of Medicine; 3Psychiatry, Yale University School of Medicine

Hypoglycemia is a serious complication of type-1 diabetes in patients with tight glycemic control. Repeated exposure to hypoglycemia may lead to increased capacity of brain cells to utilize alternate fuels such as monocarboxylic acids. In this study rates of lactate utilization were determined in rats subjected to 3-days of antecedent recurrent hypoglycemia and in controls with 1H-[13C]MRS while receiving i.v. infusions of [3-13C]lactate. Metabolic rates were assessed under euglycemic and acute hypoglycemic conditions. Our results suggest that exposure to repeated hypoglycemia leads to increased capacity of neurons to oxidize lactate, providing a possible explaination for the phenomenon of hypoglycemia unawareness.

14:30         3295.     Detection of GABA C1 Turnover in Rat Brain in Vivo

Jehoon Yang1,2, Jun Shen3

1NIMH, USA; 2Samsung Biomedical Research Institute, Korea; 3NIMH, Bethesda, MD, USA

Previous in vivo MRS studies of GABA turnover have relied on 13C label incorporation into GABA C2. In this study, the [13C]GABA C1 signal at 182.3 ppm in the carboxylic/amide spectral region of localized in vivo 13C spectra was spectrally resolved and detected in the rat brain at 11.7 Tesla using low RF power proton decoupling. GABA-transaminase of rat brain was inhibited by gabaculine after pre-labeling of GABA C1 and its precursors with [2,5-13C2]glucose. A subsequent isotope chase experiment revealed a markedly slow turnover of GABA accompanying the blockade of the GABA shunt.

15:00         3296.     Evolution of the Neurochemical Profile in the Frontal and Occipital Cortex of the Developing Mouse Determined by  in Vivo 1H NMR Spectroscopy at 14.1 T

João M. N.  Duarte1, Anita Frank2, Kim Q. Do2, Rolf Gruetter1,3

1LIFMET - CIBM, EPFL, Lausanne, Vaud, Switzerland; 2Schizophrenia Research Unit, Center for Psychiatric Neuroscience, Univ. Hosp. Lausanne, Switzerland; 3Departments of Radiology, Universities of Lausanne and Geneva, Switzerland

The present study investigated the development of the neurochemical profile composed by 20 metabolites in the frontal and occipital cortex of mice, using in vivo 1H NMR spectroscopy at 14.1T. The present data opens the possibility of studying the neurochemical profile evolution in transgenic mice modelling pathologies of the developing brain.

 
Exhibit Hall 2-3                    Wednesday 13:30-15:30          Computer 12 

13:30         3297.     Fast 13C Label Exchange Between Mitochondria and Cytosol in Brain Revealed by Saturation Transfer Spectroscopy

Jehoon Yang1,2, Su Xu1, Jun Shen3

1NIMH, USA; 2Samsung Biomedical Research Institute, Korea; 3NIMH, Bethesda, MD, USA

13C MRS has been applied to studying brain metabolism by measuring 13C label incorporation into cytosolic pools. The rate of 13C label exchange between mitochondria and cytosolic glutamate and aspartate (Vx) has been controversial. Because brain fumarase is exclusively located in the mitochondria it is possible to directly measure Vx from the four-carbon side of the tricarboxylic acid cycle (TCA) by saturation transfer. In rat brain a 13C saturation transfer effect on aspartate C2 was detected after extensive signal averaging with fumarate C2 irradiated using radiofrequency pulses. Quantitative analysis found that Vx >> the TCA cycle rate.

14:00         3298.     Hypothalamic Neuronal Activity and Intermediary Metabolism in ob/ob Mice

Inês R. Violante1, Tiago B. Rodrigues1, Laura Nieto-Charques1, Sebastián Cerdán1

1IIB "Alberto Sols", Madrid, Spain

Using a regional 13C HR-MAS approach, we compare the metabolic response of the hypothalamus in wild-type and leptin-deficient (ob/ob) mice after [1-13C]glucose administration. Mice conditioned by feeding or fasting received [1-13C]glucose (20 μmol/g body weight) and, after microwave arrest of cerebral metabolism, two areas of the brain were separated and studied, hypothalamus and remaining brain. Fasting resulted in increased lactate C3 and GABA C2 enrichments in the hypothalamus of both mice, showing that this is not a leptin-dependent effect. Ob/ob mice showed higher glutamate C4 and glutamine C4 enrichments compared to wild-type mice, revealing increased glutamate/glutamine cycling in these animals.

14:30         3299.     Measurements of Glial Metabolic Fluxes with 11C-Acetate Using Positron Emission and 1H{13C} NMR Spectroscopy

Bernard Lanz1, Lijing Xin1, Matthias T. Wyss2, Bruno Weber2,3, Alfred Buck2, Rolf Gruetter1,4

1Laboratory for functional and metabolic imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; 2PET Center, University Hospital Zurich, Division of Nuclear Medicine, Zurich, Switzerland; 3Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland; 4Departments of Radiology, Universities of Lausanne and Geneva, Lausanne and Geneva, Switzerland

Metabolic models used to quantify NMR labeling studies and PET results are usually different, based on the fundamentally different nature of the measured signal. We present here an adapted two-compartment model, based on standard NMR modeling, suitable for brain acetate metabolism studies and applicable both to positron emission and NMR measurements. The model enables the fit of both 1H{13C} NMR spectroscopy and beta-probe data and shows a good agreement in the values found for the apparent glial Krebs cycle rate.

15:00         3300.     Highly Accurate Quantification of Proton MR Spectroscopy in Rat Brain in Vivo at 16.4 T

Sung-Tak Hong1, David Zsolt Balla1, Shajan Gunamony1, Kamil Ugurbil2, Rolf Pohmann1

1Max Planck Institute for Biological Cybernetics, Tuebingen, Baden-Wuerttemberg, Germany; 2Center for Magnetic Resonance Research, Minneapolis, MN, USA

In the present study, we used a 16.4 T scanner to evaluate the quantification of metabolites from the rat brain with an ultra-short TE STEAM sequence. All metabolite resonances, previously observed in vivo and published in the literature, were detected. Additionally, a newly discernible Histidine peaks at 3.11 ppm, 3.22 ppm and 3.97 ppm were detected and quantified for the first time in vivo, with CRLB of below 20 %, indicating high quantification reliability. These preliminary results demonstrate the feasibility of detecting new metabolites in combination with the advantages of a high magnetic field strength.

 
Exhibit Hall 2-3                    Thursday 13:30-15:30          Computer 12

13:30         3301.     Subcellular Transfer of Reducing Equivalents in the Neuronal and Glial Compartments of the Adult Rat Brain After Portocaval Anastomosis and Chronic Moderate Hyperammonemia as Detected by (13C, 2H) NMR

Tiago Brandao Rodrigues1, Regina Rodrigo2, Omar Cauli2, Vicente Felipo2, Sebastián Cerdán1

1LISMAR, Instituto de Investigaciones Biomédicas CSIC, Madrid, Spain; 2Laboratory of Neurobiology, Centro de Investigación Príncipe Felipe, Valencia, Spain

We report on the effects of portocaval anastomosis and chronic moderate hyperammonemia on the transfer of reducing equivalents between the cytosolic and mitochondrial compartments from the neurons and astrocytes of the adult rat brain using a novel (13C, 2H)NMR approach. The administration of 2H2O to the animals allowed detecting and quantifying the presence of [2-13C], [2-13C,3-2H] and [2-13C,3,3’-2H2]isotopomers of glutamate and glutamine. Portocaval anastomosis results in an evident limitation in the transfer of reducing equivalents between cytosol and mitochondria of the neuronal and glial compartments, whereas hyperammonemia didn’t affect substantially this transport of reducing equivalents, both in the mitochondrial and the cytosolic compartments.

14:00         3302.     Detecting Progression of Alzheimer’s Disease Pathology in the Triple Transgenic Mouse Brain Using 1H MRS

Jieun Kim1, Sang-Pil Lee1,2, Mary L. Michaelis3, In-Young Choi1,4

1Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, USA; 2Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA; 3Department of Pharmacology and Toxocology, University of Kansas, Lawrence, KS, USA; 4Department of Neurology, Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA

Triple transgenic AD (3xTg-AD) mice model progressively develops both Ab plaques and neurofibrillary tangle pathology with accompanying neuronal death in brain regions similar to those seen in human AD. In vivo 1H MRS can provide information of neurochemical alterations in the living brain. In this study, an ultra-short echo time 1H MRS was employed to detect development of AD pathology of 3xTg-AD mice over time. Our results showed that alterations in neurochemicals such as NAA, glutamine and lactate were not pronounced at 2 months of age except taurine, but starts to be rather extensive as early as 3 months of age. The neurochemical profiles obtained by 1H MRS would provide an insight to the neurological effect in AD pathology.

14:30         3303.     Distribution of Temperature Changes and Dynamics in Rat Brain After 3,4-Methylenedioxymethamphetamine (MDMA) Injection by 1H CSI

Daniel Coman1,2, Lihong Jiang1, Fahmeed Hyder2,3, Kevin Behar4

1Department of Diagnostic Radiology, Yale University, New Haven, CT, USA; 2Quantitative Neuroscience with Magnetic Resonance (QNMR), Yale University, New Haven, CT, USA; 3Departments of Diagnostic Radiology and Biomedical Engineering, Yale University, New Haven, CT, USA; 4Department of Psychiatry, Yale University, New Haven, CT, USA

(+/-) 3,4-Methyleoxymethamphetamine (MDMA, ecstasy) use results in significant hyperthermia in muscle and brain. MDMA-induced changes on brain temperature distribution and its dynamics is of great importance in assessing its harmful CNS effects. Temperature distributions in rat brain can be obtained within minutes by using a new exogenous temperature-sensitive probe, TmDOTMA-. Our results indicate that the temperature increase in the anesthetized rat brain after a dose of 20 mg/kg MDMA is relatively homogenous, with subcortical regions showing slightly faster temperature increase than cortical regions.

15:00         3304.     Understanding Your Inhibitions. a Functional Metabolomic Approach to the GABAergic System

Caroline Rae1, Fatima Nasrallah1, Julian Griffin2, Vladimir J. Balcar3

1POWMRI, University of New South Wales, Randwick, NSW, Australia; 2The University of Cambridge, UK; 3University of Sydney, NSW, Australia

Here we report a novel method for assessing GABAergic activity by the generation of a metabolomic footprint against which the activity of ligands active in the GABA system can be compared. This approach uses a Guinea pig cortical slice model system, targeted neuropharmacology and 1H/13C NMR spectroscopy to generate a database of more than 150 functional metabolomic fingerprints, each unique to each concentration of ligand. This footprint can be used to infer actions of drugs as well as to determine how individual variables relate to GABAergic activity.

 


 
Neurodegeneration
Exhibit Hall 2-3                    Monday 14:00-16:00          Computer 13

14:00         3305.     Chronic Endogenous Glucocorticoid Treatment Induces Hippocampal Volume Loss – an in Vivo MRI Study in Rats at 7T

Mirjam I. Schubert1, Simon Beckett2, Clare Spicer2, Charles A. Marsden2, Dorothee P. Auer1

1Division of Academic Radiology, University of Nottingham, Nottingham, UK; 2School of Biomedical Sciences, University of Nottingham, Nottingham, UK

Hippocampal volume loss and memory impairment in humans and rodents supposedly result from elevated glucocorticoids. To prove this hypothesis rats were chronically treated with high-dose endogenous corticosterone and investigated for spatial memory deficits and volumetric changes in the hippocampus by in vivo MRI at 7T. Bilateral hippocampal volume loss (7-8%) and spatial memory deficits were found in corticosterone compared to vehicle treated rats supporting the hypothesis that chronic stress level endogenous glucocorticoids directly induce hippocampal volume loss associated with spatial memory deficits.

14:30         3306.     Redox-Mapping MRI in Rodent Brain with Nitroxide Contrast Agents

Hirotada G. Fujii1, Katsuya Kawanishi2, kouichi Itoh3

1Sapporo Medical University, Sapporo, Hokkaido, Japan; 2Health Sciences University of Hokkaido, Ishikari, Hokkaido, Japan; 3Tokushima Bunri University, Sanuki, Kagawa, Japan

Overproduction of reactive oxygen species (ROS) and decreased antioxidant defense system may contribute to numerous brain disorders. Non-invasive evaluation and visualization of oxidative stress is important to elucidate the role of ROS in brain diseases. The purpose of this study was to examine the ability of paramagnetic nitroxide compounds with different lipophilicities as a redox-mapping tool in MRI of brain disease animal models. The results clearly show that nitroxide contrast agents can be used not only as redox-sensitive T1 contrast agents but also as site-specific ones, and that taking redox-mapping MR images is feasible with nitroxide contrast agents.

15:00         3307.     Magnetic Resonance Analysis of the Effects of Acute Ammonia Intoxication on a Rat Brain

Pilar Lopez-Larrubia1, Omar Cauli2, Tiago Brandao Rodrigues1, Sebastian Cerdan1, Vicente Felipo2

1Biomedical Research Institute, Madrid, Spain; 2Centro de Investigacion Principe Felipe, Valencia, Spain

Acute ammonia intoxication leads to rapid death, which is prevented by blocking NMDA receptors. The aim of this work was to study the effects of acute ammonia intoxication on different cerebral parameters in vivo using magnetic resonance. We analyzed the effects on ADC, T1 and T2 maps in 16 brain areas. We also studied brain metabolites detected by in vivo spectroscopy and whether if these effects are prevented by blocking NMDA receptors. Changes in . N-acetyl-aspartate, T1 and T2 are prevented by blocking NMDA receptors with MK-801 while changes in ADC or myo-inositol (induction of edema) are not.

15:30         3308.     Aluminum Mediated Changes in Rat Brain Using MRI/ MTC Imaging

Deepa Prajapati1, Sanjay Annarao1, Sandeep Tripathi2, Abbas Ali Mahdi2, Farzana Mahdi3, Mahdi Hasan4, Raja Roy1, C L. Khetrapal1

1CBMR, Centre of Biomedical Magnetic Resonance, LUCKNOW, U.P., India; 2Biochemistry, Chattrapati Shahuji Maharaj Medical University, LUCKNOW, U.P., India; 3Biochemistry, Era’s Lucknow Medical College and Hospital, LUCKNOW, U.P., India; 4Anotomy, Chattrapati Shahuji Maharaj Medical University, LUCKNOW, U.P., India

Aluminum induced alterations in rat brain have been studied by MRI using MT effect in rats administering Al3+ in three different ways i.e. Al3+ alone, Al3+with Bacoside, Al3+with Donepezil and the results were compared with positive control. MTR has been evaluated successively for three months. Statistically, significant differences were observed in MTR of second and third month in Al3+ treated group and in MTR of Al3+ and B treated group during third month. The results indicate Al3+ overload has implications similar to AD. The effect of Donepezil and Bacoside is indicative of their different mode of action in memory restoration.

 
Exhibit Hall 2-3                    Tuesday 13:30-15:30          Computer 13

13:30         3309.     Relationship of Functional Activation Deficit and Anatomical Atrophy in the Primary Olfactory Cortex and Hippocampus of Alzheimer’s Disease.

Jianzhong Yin1,2, Jianli Wang1, Paul Eslinger3, Lindsi DeArment1, Erin Zimmerman1, Jeffery Vesek1, Ji Qi2, James Connor4, Qing X. Yang1

1Center for NMR Research, Departments of Radiology, Penn State College of Medicine, Hershey, PA, USA; 2Department of Radiology, Tianjin First Central Hospital, Tianjin, China; 3Departments of Neurology, Penn State College of Medicine, Hershey, PA, USA; 4Departments of Neurosurgery, Penn State College of Medicine, Hershey, PA, USA

Olfactory deficit is prevalent at the very early stage in the Alzheimer’s disease. The pathological changes occur in the medial temporal lobe, including the primary olfactory cortex (POC) and hippocampus result in the malfunction of olfaction as well as the cognitive functions. In this study, we will systemically measure the POC and hippocampus volume in the AD and normal subjects and statistic the activation voxels in these regions, so that to investigate the relationship of the functional and anatomical changes at the POC and hippocampus regions.

14:00         3310.     T1ρ (T) MRI and CSF Analysis in Prediction of Alzheimer’s Disease at Early Stage

Mohammad Haris1, Erin McArdle1, Matthew Sochor1, Matthew Fenty1, Anup Singh1, Christos Davatzikos2, John Q. Trojanowski3, Elias R. Melhem, Christopher M. Clark4, Ravinder Reddy1, Arijitt Borthakur1

1MMRRCC, Radiology, University of Pennsylvania, Philadephia, PA, USA; 2SBIA, Radiology, University of Pennsylvania, Philadephia, PA, USA; 3Department of Pathology & Lab Medicine, University of Pennsylvania, Philadephia, PA, USA; 4Department of Neurology, University of Pennsylvania, Philadephia, PA, USA

Alzheimer’s disease (AD) is the most common form of disabling cognitive impairment in older people. In the current study, we have evaluated the role of T1rho (T) and CSF biomarker in early diagnosis of AD. The current study suggests the combined role of T and CSF biomarkers in early and more specific diagnosis of AD.

14:30         3311.     Early Marker for Alzheimer’s Disease: Hippocampus T1ρ (T ) Estimation

Mohammad Haris1, Erin McArdle1, Matthew Sochor1, Matthew Fenty1, Anup Singh1, Christos Davatzikos2, John Q. Trojanowski3, Elias R. Melhem, Christopher M. Clark4, Ravinder Reddy1, Arijitt Borthakur1

1MMRRCC, Radiology, University of Pennsylvania, Philadephia, PA, USA; 2SBIA, Radiology, University of Pennsylvania, Philadephia, PA, USA; 3Department of Pathology & Lab Medicine, University of Pennsylvania, Philadephia, PA, USA; 4Department of Neurology, University of Pennsylvania, Philadephia, PA, USA

For treatment of AD to be most effective, it is believed that the regimen must be started before clinical diagnosis of AD, at the stage of MCI. In the current study, we measured T1rho (T) relaxation time in the hippocampus of control, MCI and AD cohorts. The AD individuals showed significantly higher T value compared to control and MCI. A significant increased T value was also observed in MCI compared to control. We suggest that the measurement of hippocampus T relaxation time may provides a marker in the early diagnosis of AD.

15:00         3312.     T1ρ (T) MR Imaging in Alzheimer’ Disease and Parkinson’s Disease

Anup Singh1, Mohammad Haris1, Erin McArdle1, Matthew Sochor1, Matthew Fenty1, Christos Davatzikos2, John Q. Trojanowski3, Elias R. Melhem, Christopher M. Clark4, Ravinder Reddy1, Arijitt Borthakur1

1MMRRCC, Radiology, University of Pennsylvania, Philadephia, PA, USA; 2SBIA, Radiology, University of Pennsylvania, Philadephia, PA, USA; 3Department of Pathology & Lab Medicine, University of Pennsylvania, Philadephia, PA, USA; 4Department of Neurology, University of Pennsylvania, Philadephia, PA, USA

Structural neuroimaging has the potential to play an important role in the early diagnosis of both AD and PD. In the current study, we measured the T1rho (T) value in MTL in the brain of control, Parkinson's disease (PD) and Alzheimer's disease (AD). T was significantly increased in AD compared to control and PD. The PD individuals showed decreased T compared to control. We conclude that the serial measurement of T in both AD and PD may provide the nature of disease progression and would contribute to their early diagnosis in the future.

 
Exhibit Hall 2-3                    Wednesday 13:30-15:30          Computer 13

13:30         3313.     Reduced Resting-State Connectivity in the Brain's Default Mode Network in Patients with Mild Forms of Relapsing-Remitting MS

Michael Amann1,2, Jochen Gunther Hirsch1,2, Lea Sybil Doessegger3, Iris Katherina Penner3, Katrin Weier2, Ernst Wilhelm Radue1, Ludwig Kappos2, Achim Gass1,2

1Neuroradiology, University Hospital Basel, Basel, BS, Switzerland; 2Neurology, University Hospital Basel, Basel, BS, Switzerland; 3Department of Cognitive Psychology, University of Basel, Basel, BS, Switzerland

In this work, we investigated resting state connectivity in brain’s default mode network in order to evaluate whether altered connectivity may be present in patients with mild forms of relapsing-remitting multiple sclerosis (RR-MS). Differences in functional connectivity to posterior cingulate cortex (PCC) were calculated in two different ways. Both in voxel based and in ROI analysis, we found reduced strength of connectivity (p<0.05) to PCC in anterior cingulate cortex and in an adjacent part of medial frontal gyrus for RR-MS patients compared to healthy controls.

14:00         3314.     Functional Plasticity in the Human Motor System After Transfer of Intercostal Nerves to the Biceps Muscle

Mattijs Elschot1,2, Serge A R B Rombouts3,4, Martijn JA Malessy5, Catrien A. Schimmelpenninck3,6, Matthias J P van Osch3,4, Ivan Toni1, David G. Norris1,7, Mark A. van Buchem3, Pieter F. Buur1,3

1Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, Netherlands; 2Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands; 3Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands, Leiden, Netherlands; 4Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands, Leiden, Netherlands; 5Department of Neurosurgery, Leiden University Medical Center, Leiden, Netherlands; 6Department of Radiology, Leiden University Medical Center, Leiden, Netherlands; 7Erwin L. Hahn Institute for Magnetic Resonance, University Duisburg-Essen, Essen, Germany , Essen, Germany

The functional reorganization of the motor system in patients that have undergone a nerve transfer from the intercostal muscles to the biceps to restore biceps function is investigated. In these patients, control over the biceps progresses from a stage in which it is coupled to deep breathing to a state of volitional control. Differences in brain activity between patients and a control in multiple areas of the motor network group when performing biceps contraction indicate suggest cortical plasticity related to the functional recovery. These results give more insight in the underlying mechanisms of cortical reorganization following peripheral injury.

14:30         3315.     Evaluation of Therapy Effects in Patients with Chronic Spatial Neglect Using FMRI as a Quantitative Tool

Julia Reinhardt1, Martina Wengenroth1, Gundhild Leifert-Fiebach2, Peter Schneider1, Maria Blatow1, Anouk Welfringer2, Ralf Babinsky2, Tobias Brandt2, Christoph Stippich1

1Department of Neuroradiology, University of Heidelberg Medical School, Heidelberg, Baden Württemberg, Germany; 2Kliniken Schmieder, Heidelberg, Germany

Spatial neglect is a neurological disorder caused by lesions in right-hemispheric association areas resulting in neglect and decreased usage of the left side of the body. Employing an established functional MRI paradigm we were able to detect and quantify pre and post therapeutic motor imagery activations which we used to quantify therapy effects in eight patients with chronic neglect. We therefore propose that fMRI can be used as an objective and independent tool to monitor post-therapeutic changes on the neurobiological level.

15:00         3316.     Effects of Cranial-Nerve Non-Invasive Neuromodulation (CN-NINM) on Neural Activity as Measured by BOLD-FMRI

Joseph Wildenberg1,2, Mitch Tyler3,4, Yuri Danilov3, Mary Meyerand1,5

1Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, USA; 2Medical Scientist Training Program, University of Wisconsin-Madison, Madison, WI, USA; 3Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI, USA; 4Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA; 5Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA

Neurostimulation through the tongue provides a non-invasive route to modulate activity within the brainstem and higher cortical areas. This study investigated the residual changes in neural activity after the stimulation has been removed in patients with vestibular dysfunction in response to optical flow. We found long-term neuromodulation of the dorsal pons that may explain the lasting symptomatic improvement seen in vestibular patients after neurostimulation through the tongue.

 
Exhibit Hall 2-3                    Thursday 13:30-15:30          Computer 13

13:30         3317.     Analyses of Susceptibility-Induced Effects on DTI Indexes in Patients with Neurodegenerative Diseases

Songfan Xu1, Geon-Ho Jahng2, Norbert Schuff3, Dieter J. Meyerhoff4, Michael W. Weiner4

1Department of Medical Research Center, Kyung-Hee University, Seoul, Korea; 2Radiology, East West Neo Medical Center, Kyung Hee University, Seoul, Korea; 3Radiology, CIND, Veterans Affairs Medical Center, UCSF, San Francisco, CA, USA; 4Radiology, CIND, Veterans Affairs Medical Center, UCSF, San Francisco, CA, Korea

To evaluate the susceptibility-induced effects on DTI indexes in patients with Alzheimer¡¯s disease (AD) and mild cognitive impairment (MCI), we obtained mean diffusivity (MD) and FA maps with using two polarities of diffusion-sensitizing gradients for AD, MCI patients, and cognitive normal (CN) controls. After finding the locations of differences of MD or FA maps between two polarities, we specified the region of interest (ROI) at the locations, and got signals from raw DTI data for ROI and the opposite location in the same samples as well as for ROI in all three groups to compare.

14:00         3318.     Fiber Bundle Atrophy in Friedreich’s and Spinocerebellar Ataxia

Elisabetta Pagani1, Andrea Ginestroni2, Federica Agosta1, Mario Mascalchi2, Massimo Filippi1

1Neuroimaging Research Unit, Scientific Institute and University Hospital San Raffaele, Milan, Italy; 2Radiodiagnostic Section, Department of Clinical Physiology, University of Florence, Florence, Italy

We studied the spatial distribution of fiber bundle atrophy in patients with Friedreich’s and spinocerebellar ataxia. The method used is based on anisotropy maps derived from diffusion tensor images to contrast fiber bundles and on a non-linear registration to calculate differences in comparison with an atlas. The analysis was run considering the whole brain first, and the cerebellum only thereafter. Consistent with pathological findings, both the analyses showed the involvement of the pons, the medulla and cerebellar peduncles. The spatial distribution of atrophy in each group was even better differentiated when the cerebellum was studied in isolation.

14:30         3319.     Similar Microstructure Abnormality of Anterior Cingulate Region in Depressed and Undepressed Parkinson's Disease: Evidence from Diffusion Tensor Imaging

JiangTao Liu1, KunCheng Li2

1Radiology, Xuan Wu Hospital, Beijing, China; 2radiology, Xuanwu hospital, beijing, China

Objectives We aimed to compare the fractional anisotropy (FA) values of depressed Parkinsno's disease(DPD) and non-depressed Parkinson's disease(UDPD) to certain the anterior cingulate cortex(ACC) bundle microstructrue changes. Methods 15 DPD, 14 UDPD and 21 normal controls (NC) were included in the present study.. Results Comparing with NC group, DPD and UDPD both showed reductions in FA values in the ROIs representing the ACC bundles. The DPD group has lower FA value in the ROIs comparing with UDPD group. Conclusions UDPD may have cortical microstructrue changes involved in part of the emotion regulation circuit.

15:00         3320.     Abnormalities of Supratentorial White Matter in Multiple System Atrophy: Diffusion Tensor Imaging Observation

Khin Khin Tha1, Satoshi Terae1, Ichiro Yabe2, Tamaki Miyamoto3, Hiroyuki Soma2, Yuri Zaitsu1, Noriyuki Fujima1, Hidenao Sasaki2, Hiroki Shirato1

1Department of Radiology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan; 2Department of Neurology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan; 3Department of Physiology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan

Autopsies have shown that abnormalities in multiple system atrophy (MSA) are not confined only to the infratentorial compartment and putamen, but can also be observed in the supratentorial white matter. This study evaluated if DTI can detect supratentorial white matter abnormalities in MSA, and their clinical significance. Supratentorial white matter, including centrum semiovale, external and internal capsules, of MSA patients had significant FA and D alterations, some of which were significantly correlated with the activity of daily living. Attention should also be paid to supratentorial white matter abnormalities in assessment of MSA. DTI can be useful in detecting these abnormalities.

 


 
Neurodegenerative Disorders
Exhibit Hall 2-3                    Monday 14:00-16:00          Computer 14

14:00         3321.     The Role of Structural Disconnection Secondary to Regional Grey Matter Loss in the Progression of Alzheimer's Disease

Laura Serra1, Mara Cercignani1, Tommaso Gili2, Roberta Perri3, Lucia Fadda3, Carlo Caltagirone3,4, Marco Bozzali1

1Neuroimaging Laboratory, Fondazione Santa Lucia, Roma, Italy; 2MarbiLab, Enrico Fermi Centre, Roma, Italy; 3Clinical and Behavioural Neurology Laboratory, Fondazione Santa Lucia, Roma, Italy; 4Dept of Neuroscience, University of Rome 'Tor Vergata', Roma, Italy

Whole-brain voxel-based MRI investigations of AD have shown that medial and temporal areas are the sites of earliest atrophy, while positron emission tomography (PET) studies of early AD have pointed at the posterior cingulate-precuneus area as a region characterised by early metabolic alterations. This study aims at assessing the involvment of the cingulum bundle, a white matter structure connecting anterior and posterior cingulate cortices during AD progression. To this aim we used voxel-based morphometry and diffusion tractography in patients with AD and mild cognitive impairment.

14:30         3322.     DTI Studies in Patients with Alzheimer's Disease, Mild Cognitive Impairment, and Cognitive Normal with Minimizing Contributions of Background Gradients

Songfan Xu1, Geon-Ho Jahng2, Norbert Schuff3, Dieter J. Meyerhoff3, Michael W. Weiner3

1Department of Medical Research Center, Kyung-Hee University, Seoul, Korea; 2Radiology, East West Neo Medical Center, Kyung Hee University, Seoul, Korea; 3Radiology, CIND, Veterans Affairs Medical Center, UCSF, San Francisco, CA, USA

DTI studies can be confounded by local background gradients that may relate to brain abnormalities. We studied DTI maps of patients with Alzheimer¡¯s disease (AD), mild cognitively impairment (MCI) and cognitive normal (CN) subjects by comparing between maps derived from either positive or negative polarities of diffusion gradients or from geometric diffusion means that minimize background gradients. We found that background gradients were significantly enhanced in AD when compared to MCI or CN subjects, implying that AD pathology may contribute to local background gradients. Background gradients need to be considered when interpreting DTI data in AD.

15:00         3323.     Comparison of Brain Metabolism and Atrophy in Prodromal Alzheimer's Disease

David S. Karow1, Linda K. McEvoy1, Christine Fennema-Notestine2, Donald J. Hagler, Jr. 1, Robin G. Jennings1, Carl K. Hoh1, Anders M. Dale1,3

1Department of Radiology, University of California, San Diego, La Jolla, CA, USA; 2Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; 3Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA

Potential MRI-derived, ROI-based biomarkers for the diagnosis of early Alzheimer's Disease.

15:30         3324.     Whole Brain N-Acetylaspartate Quantification Comparison Between Healthy Elderly, Mild Cognitively Impaired and Alzheimer’s Patients: Evidence for Different Clinical Cohorts

Amit Gokhale1, Lidia Glodzik1, Songtao Liu1, Juchen Hirsch2, L Achtnichts2, A Monsch3, Achim Gass2, Oded Gonen1

1Radiology, NYU School of Medicine, New York, NY, USA; 2Neurology, University of Basel, Basel, Switzerland; 3Neurology, University of Basel, Basel, Bas, Switzerland

The very large - in the millions and fast-growing number of Alzheimer’s disease (AD) patients motivates a search of preferably non invasive markers that could detect the diseases at its earliest possible stage. Since, AD is known to be a neuronal dysfunction; MR spectroscopy has a specific marker for it– the N-acetylaspartate (NAA). Furthermore, since AD is a diffuse disorder, whole-brain NAA (WBNAA) spectroscopy is the most appropriate tool. In this study we applied WBNAA to controls, Mild cognitively impaired individuals (believed to be “early AD”) and AD patients to quantify the detectable differences between these three populations.

 
Exhibit Hall 2-3                    Tuesday 13:30-15:30          Computer 14

13:30         3325.     Proton Magnetic Resonance Spectroscopy Along the Pyramidal Tract of Patients with Amyotrophic Lateral Sclerosis

Michal Bittsansky1,2, Stefan Sivak1, Hubert Polacek1,3, Monika Turcanova-Koprusakova1, Egon Kurca1, Dusan Dobrota1

1Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia; 2MR Centre of Excellence, Medical University of Vienna, Vienna, Austria; 3Clinic of Radiodiagnostics, Martin Faculty Hospital, Martin, Slovakia

We compared 1H MR-spectra from different regions along the pyramidal tract of ALS patients to healthy volunteers and to the patients’ clinical score of the disease (ALSFRS). We found significantly different values of NAA:Cre and NAA:Cho in certain brain regions of ALS patients compared to healthy controls. We also found high correlation of NAA:Cre in the right motoric area of the brain to the patients’ ALSFRS score and its subscores for fine and gross motorics.

14:00         3326.     Proton Magnetic Resonance Spectroscopy (1H-MRS) on the Spinal Cord in Amyotrophic Lateral Sclerosis (ALS) at 3T

Nashiely Pineda Alonso1, Michael Benatar2, Xiaoping Hu1, John Carew3

1Biomedical Engineering, Emory University, Atlanta, GA, USA; 2Neurology, Emory University, Atlanta, GA, USA; 3Biostatistics, Emory University, Atlanta, GA, USA

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by a degeneration of both upper and lower motor neurons in the brain, brainstem and spinal cord. 1H-MRS has not previously been applied in the spinal cord of patients with ALS. The findings of the present study are consistent with the results of previous studies using 1H-MRS for the brain, medulla and brainstem metabolism analysis of ALS patients. Reductions in NAA and higher Glx and Inositol signals were found in ALS patients. The present study showed the feasibility of the MRS applied to the spinal cord of ALS patients with standard PRESS sequence at 3T.

14:30         3327.     Correlation of MRS Markers with HIV DNA in Patients Well-Controlled on HAART

napapon Sailasuta1, Victor Valcour2, Bruce Shiramizu2, Aaron McMurtray2, James Taylor2, Kalpana Kallianpur2, Cecilia Shikuma2

1HMRI, Pasadena, CA, USA; 2U of Hawaii, Honolulu, HI, USA

Correlation of brain glutamate and HIV RNA

15:00         3328.     MR Spectroscopy of GABA and Other Brain Metabolites in Smelters Exposed to Manganese

Ulrike Dydak1,2, Liling Long3, Henry Zhu4, Wenmei Li3, Yueming Jiang5, Jian Chen6, X. Fu1, Shuguang Hu7, Richard A.E. Edden8, Dieter Meier9, Michael Aschner10, James Murdoch11, Wei Zheng1

1School of Health Sciences, Purdue University, West Lafayette, IN, USA; 2Dep. of Radiology, Indiana University School of Medicine, Indianapolis, IN, USA; 3Dep. of Radiology, Guangxi Medical University, Nanning, China; 4Dep. of Radiology, Johns Hopkins University, Baltimore, MD, USA; 5Dep. of Occup. Health and Toxicology, Guangxi Medical University, Nanning, China; 6Guizhou Inst. of Occup. Safety and Health, Zunyi, China; 7Philips Healthcare, China; 8Schools of Biosciences and Chemistry, Cardiff University, UK; 9Inst. for Biomed. Engineering, ETH and University Zuerich, Switzerland; 10Dep. of Pediatrics, Vanderbilt University, Nashville, TN, USA; 11Philips Healthcare, Cleveland, OH, USA

GABA-edited magnetic resonance spectroscopy (MRS) in the basal ganglia was combined with single voxel MRS of five different brain areas and high-resolution 3D T1-weighted imaging at 3T to assess changes in neurotransmitters and other brain metabolites, as well as the spatial distribution of T1 hyperintensities due to occupational manganese exposure in a cohort of smelters. Extensive signal hyperintensities in globus pallidus, striatal and midbrain regions were found in 8 out of 10 exposed subjects. Findings on changes in metabolism include significantly increased GABA/Cr in the thalamic area of the exposed subjects, as well as decreased NAA/Cr in frontal cortex (p<0.05).

 
Exhibit Hall 2-3                    Wednesday 13:30-15:30          Computer 14

13:30         3329.     Age-Related Microstructural Alterations Increase the Relationship Between Radial and Axial Diffusivities.

Agnieszka Zofia Burzynska1, Claudia Preuschhof1, Lars Bäckman1,2, Lars Nyberg3, Shu-Chen Li1, Ulman Lindenberger1, Hauke Reiner Heekeren1,4

1Max Planck Institute for Human Development, Berlin, Germany; 2Aging Research Center, Karolinska Institute, Stockholm, Sweden; 3Department of Radiation Sciences and Integrative Medical Biology , Umeå, Sweden; 4Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany

Using tract-based-spatial-statistics we obtained the center-of-tract radial and axial diffusivity from 80 younger and 63 older adults. We found that the correlation of radial with axial diffusivity was higher in older than in younger adults for all investigated regions. This observation was independent of the direction of mean age differences in both DTI measures and thus may reflect a general age-related microstructural alteration common to most white matter regions, such as an increase in the extracellular space. The white matter diffusivity properties in late adulthood may result from tract-specific combination of fiber geometry and age-related alterations.

14:00         3330.     Dissociation Between Aging of Anterior and Posterior Corpus Callosum Microstructure Depends on Genotype

Kristen Michelle Kennedy1, Karen Michelle Rodrigue1, Susan Land2, Naftali Raz3

1Center for BrainHealth, School of Behavioral and Brain Science, University of Texas at Dallas, Dallas, TX, USA; 2Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; 3Institute of Gerontology and Dept of Psychology, Wayne State University, Detroit, MI, USA

Mechanisms of differential brain aging are poorly understood, but may be under genetic control. Genetic predisposition to reduced levels of brain-derived neurotrophin factor and increased cytokine proinflammation may exacerbate the pattern and trajectory of normal aging. We used DTI and genotyping to explore the association between genu and splenium corpus callosum white matter integrity and BDNFval66met and IL-1Beta A/G polymorphisms. Anterior callosum integrity declined with normal aging, but posterior decline was associated selectively with genetic risk in BDNF66met+ and IL-1Beta G+ genotypes. These genotypes were also associated with accelerated age-related declines, whereas the non-risk genotypes evidenced linear declines.

14:30         3331.     Variation in DTI-FA as a Function of Age and Brain Region: Setting the Stage for Mild TBI

Randall R. Benson1, Ramtilak Gattu2, Naftali Raz3, Kristen M. Kennedy3, Zhifeng Kou4, Ewart M. Haacke4,5

1Neurology, Wayne State University, Detroit, MI, USA; 2Radiology, Wayne State University/MR Research Facility, Detroit, MI , USA; 3Gerontology, Wayne State University, Detroit, MI, USA; 4MR Research Facility, Wayne State University, Detroit, MI, USA; 5MRI Institute for Biomedical Research, Wayne State University, Detroit, MI, USA

This study investigates regional fractional anisotropy using 50 healthy volunteers and also explores age effects on 38 white matter regions.

15:00         3332.     Sensorimotor Network Rewiring in Patients with Mild Cognitive Impairment and Alzheimer’s Disease

Federica Agosta1, Maria Assunta Rocca1, Elisabetta Pagani1, Martina Absinta1, Maria Luisa Gorno-Tempini2, Giuseppe Magnani3, Alessandra Marcone4, Monica Falautano3, Giancarlo Comi3, Massimo Filippi1

1Neuroimaging Research Unit, Scientific Institute and University Hospital San Raffaele, Milan, Italy; 2Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA; 3Department of Neurology, Scientific Institute and University Hospital San Raffaele, Milan, Italy; 4Division of Neurology, San Raffaele Turro Hospital, Milan, Italy

F-MRI and effective connectivity analyses were used to investigate the sensorimotor network in 10 Alzheimer’s disease (AD), 15 amnestic mild cognitive impairment (aMCI), and 11 controls. An increased activation of several sensorimotor regions were found in aMCI vs. controls and AD. Abnormal connectivity was revealed between left primary motor cortex, caudate nucleus and cingulate motor area in both patient groups. fMRI metrics correlated with hippocampi atrophy in aMCI, and overall grey matter damage in AD. This suggests the occurrence of a widespread brain rewiring with increasing structural damage rather than a “specific” response of the cognitive network to MTL injury.

 
Exhibit Hall 2-3                    Thursday 13:30-15:30          Computer 14

13:30         3333.     Hemi-Parkinson’s Disease Rat Model: Correlation Between Behaviour, Histology and MRI

Giuseppina Confalone1, Daniela Minchella1, Tiziana Florio1, Eugenio Scarnati1, Antonello Sotgiu2, Marcello Alecci2

1Dipartimento di Scienze e Tecnologie Biomediche, University of L’Aquila, L’Aquila, Italy; 2Dipartimento di Scienze della Salute, University of L’Aquila, L’Aquila, Italy

In this work we have developed a behavioural paradigm in a Hemi-PD rat model coupled with immuno-histological staining and MRI methods, to evaluate anatomical and physiological data. This Hemi-PD model in the rat should be useful to investigate difficulties raising in PD patients during the shifting from a mental set to another.

14:00         3334.     Microanatomy of the Primate Mouse Lemur Brain at 7T After Passive Staining

Anne Bertrand1,2, Alexandra Petiet1,3, Sébastien Mériaux2, Christopher J. Wiggins2, Audrey Kraska1,2, Olène Dorieux1,2, Fabienne Aujard4, Marc Dhenain1,2

1CNRS URA2210, MIRCen, Orsay, France; 2Neurospin, I2BM, CEA, Gif-sur-Yvette, France; 3Sanofi-Aventis R&D, Vitry-sur-Seine, France; 4UMR CNRS/MNHN 7179, Mecadev, Brunoy, France

Mouse lemurs provide a promising primate model of Alzheimer's disease. We performed a morphological micro-MRI ex vivo study on 6 mouse lemur formalin-fixed brains using gadolinium passive staining (PS). Quantitative analysis showed that PS increased the contrast-to noise ratio (CNR) between grey and white matter, even in very small white matter tracts. Qualitative analysis showed that structures as small as the dentate gyrus and olfactory bulb cell layers could be resolved on a 3D FLASH sequence. Our results should be useful in preclinical studies using this primate model of AD.

14:30         3335.     Quantitative Phenotype Characterization of Developing Mouse Brains by Diffusion Tensor Imaging: Application for the Frizzled-4-/-  Mutant Mice

Manisha Aggarwal1, Xin Ye2, Jeremy Nathans2,3, Michael I. Miller1,4, Susumu Mori5, Jiangyang Zhang5

1Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Department of Molecular Biology & Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 3Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 4Center of Imaging Science, Johns Hopkins University, Baltimore, MD, USA; 5Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Population-based quantitative analyses of DTI data was used to characterize phenotypic changes during development in the Frizzled-4 knockout (Fz4-/-) mutant mouse brain. Population-averaged anisotropy indices computed from normalized diffusion tensor fields for wild type and Fz4-/- mouse brains at postnatal day 7 (P7), P14, P21 and P30 were used to investigate the developmental abnormalities at each stage. DTI results indicated progressive disorganization of the cerebellar cellular architecture, consistent with previous histological findings, and revealed developmental anomalies characterized by differences in diffusion anisotropy in the dentate gyrus, olfactory bulb and several axonal tracts.

15:00         3336.     Diffusion Tensor Imaging Detects Axonal Injury and Demyelination in the Spinal Cord and Brain of a Murine Model of Globoid Cell Leukodystrophy.

Joong Hee Kim1, Alex A. Hofling1, Mark S. Sands2, Sheng-Kwei Song1

1Radiology, Washington University, St. Louis, MO, USA; 2Divisions of Hematology and Oncology, Washington University, St. Louis, MO, USA

The spinal cord of Twitcher mice, an animal model of Globoid cell leukodystrophy, was examined by DTI. Compared to control Twitcher mice displayed a statistically significant increase in radial diffusivity and decrease in axial diffusivity at spinal cord white matter. These changes correlate with histopathological evidence of demyelination and axonal damage, respectively in the Twitcher spinal cord. Fractional anisotropy, a nonspecific but rotationally invariant indicator of white matter disease, was significantly reduced throughout the spinal cord white matter of Twitcher mice relative to normal controls. These results suggest DTI as noninvasive technique that is sensitive to white matter disease processes.

 


 
Neurodegenerative Disorders
Exhibit Hall 2-3                    Monday 14:00-16:00          Computer 15

14:00         3337.     Correction of MRI Scaling Parameters: A Comparison of Phantom and Registration Methods on the ADNI Dataset

Matthew J. Clarkson1,2, Casper Nielsen1, Kelvin L. Leung1,2, Josephine Barnes1, Jennifer L. Whitwell3, Jeffrey Gunter3, Clifford R. Jack3, Nick C. Fox1, Sebastien Ourselin1,2

1Dementia Research Centre, University College London, London, UK; 2Centre For Medical Image Computing, University College London, London, UK; 3Mayo Clinic College Of Medicine, Rochester, MN, USA

Rates of brain atrophy from serial MR studies may be confounded by scanner drift. This is the first study to directly compare voxel size correction using a phantom to a 9 degrees of freedom (DOF) registration algorithm, using multi-site data (ADNI). These results show that 9DOF registration is comparable to a phantom with no significant differences in brain atrophy measurements, and that there is no significant difference in the scaling correction for control and Alzheimer's disease subjects. This implies that registration is a viable alternative, which can be applied as a post-processing alternative to scanning a phantom.

14:30         3338.     Correcting for Partial Volume Effects in Arterial Spin Labeling Perfusion Imaging of Alzheimer's Disease

Iris Asllani1, Christian G. Habeck, Nicolaos Scarmeas, Truman R. Brown, Yaakov Stern

1Columbia University, New York, NY, USA

Pure gray matter CBF images, independent of voxel tissue heterogeneity, were obtained using partial volume corrected arterial spin labeling (ASL) MRI from patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) and compared with those from age-matched healthy controls (HC). Results from ROI and voxelwise analysis are shown. We also investigated the effects of gender and brain atrophy on the observed CBF differences among the three groups.

15:00         3339.     Prediction of Conversion from Mild Cognitive Impairment to Alzheimer’s Disease Based on Regional Brain Volume Measured on MRI and MRI-Guided Perfusion Measured by SPECT

Huali Wang1,2, Ke Nie1, Malcolm B. Dick3, Mark Mandelkern1, Orhan Nalcioglu1, Min-Ying Lydia Su1

1Tu & Yuen Center for Functional Onco-Imaging, University of California, Irvine, CA, USA; 2Department of Geriatric Psychiatry, Peking University Institute of Mental Health, Beijing, China; 3Institute for Brain Aging and Dementia, University of California, Irvine, CA, USA

MRI and SPECT scans were performed on 13 MCI and 12 NC. Of the MCI patients, 10 were followed for up to three years and 4 subsequently converted to AD. The results demonstrated that volume reductions and hypoperfusion were mainly confined to the medial temporal lobe of MCI patients and associated with worse scores on tests of recent memory. The 4 MCI-AD converters had relatively low structural volume and perfusion in the medial temporal lobe compared to their stable peers, supporting that imaging measures should be included as diagnostic criteria to identify patients who have prodromal or preclinical AD.

15:30         3340.     Body Mass Index and Neuronal Viability in Healthy Cognitively Normal Elderly- A Magnetic Resonance Spectroscopy Study

Stefan Gazdzinski1, Rachel Millin1, Lana Kaiser2, Michael W. Weiner1,2, Dieter J. Meyerhoff1,2

1Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA; 2Radiology, University of California, San Francisco, CA, USA

Recent studies suggest that excessive body weight in otherwise healthy individuals is associated with brain structural alterations, poorer executive function, lower prefrontal neurometabolism, and as we have previously demonstrated, with widespread decreases in concentrations of N-acetyl-asparte (NAA, marker of neuronal viability), especially in frontal lobe. In this elderly cohort, we have demonstrated associations between higher body mass index (BMI) and lower NAA and glutamate (scaled to choline and creatine) in anterior cingulate cortex, a region involved in emotional regulation, impulse control, and goal directed behavior. Thus our results may point to mechanisms leading to development and maintenance of weight problems.

 
Exhibit Hall 2-3                    Tuesday 13:30-15:30          Computer 15

13:30         3341.     Deconvolved SWI Phase Model of Patients with Parkinson Disease

Guenther Grabner1,2, Siegfried Trattnig1, Markus Barth2

1Department of Radiology, Medical University of Vienna, Vienna, Austria; 2Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, Netherlands

A phase model based on 27 individual Parkinson disease (PD) SWI phase data sets was developed which reduces the workload for ROI definition and should reduce intra- and inter-observer variability. This resulting high SNR phase model could be deconvolved reliably using a filtered deconvolution which significantly reduced the influence of the dipolar phase pattern and improved definition of ROIs near tissue boundaries. Phase differences increased by a factor of two in SN and GP in PD patients compared to values in healthy volunteers and were more accurate using the phase model compared to assessment on individual data sets.

14:00         3342.     The Diagnostic Utility of Susceptibility Weighted Imaging (SWI) in Amyotrophic Lateral Sclerosis.

Akiko Jingu1, Makoto Amanuma1, Keigo Endou2

1Diagnostic Radiology, Gunma University Hospital, Maebashi-shi, Gunma, Japan; 2Diagnostic Radiology, Gunma University Hospital, Japan

To evaluate the susceptibility weighted images (SWI) for diagnosis of amyotrophic lateral sclerosis (ALS) and determine whether the low signal intensity of precentral gyral cortex on T2WI is due to susceptibility effect. Nine patients with ALS and thirty control subjects were studied. On SWI, all ALS patients showed decreased signal intensity of precentral gyral cortices and gray matter-white matter contrast ratio was significantly higher than that of non ALS patients (p<0.001).

14:30         3343.     Minocycline Reveals Neuroprotection in an Accelerated Rhesus Macaque Model of NeuroAIDS by 1H MR Spectroscopy

Eva-Maria Ratai1, Chan-Gyu Joo1, Jeffrey Bombardier1, Julian He1, Lakshman Annamalai2, Tricia H. Burdo3, Jennifer H. Campbell3, Caroline Soulas3, Patrick Autissier3, Susan V. Westmoreland2, Kenneth Williams3, R. Gilberto Gonzalez1

1Radiology, Massachusetts General Hospital - A.A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA; 2New England Regional Primate Research Center, Southborough, MA, USA; 3Biology Department, Boston College, Boston, MA, USA

Untreated simian immunodeficiency virus leads to neuronal injury which can be detected by in vivo MR Spectroscopy (MRS) by a decrease in neuronal marker N-Acelylaspartate/Creatine (NAA/Cr). Using in vivo, single voxel 1H MRS in an accelerated macaque model of neuroAIDS, we found that minocycline, a well-tolerated, inexpensive anti-inflammatory tetracycline-type antibiotic prevents neuronal injury. In all four brain regions measured, NAA/Cr was elevated compared to an untreated control cohort. In addition, markers of inflammation/gliosis such as Cr and choline declined to normal levels after treatment by minocycline.

15:00         3344.     High B-Value Cerebral DWI and Basal Nuclei ADC Measurements in Variant and Sporadic Creutzfeldt-Jakob Disease

Harpreet Hyare1,2, John Thornton2,3, Durrenajaf Siddique1, John Stevens2, John Collinge1, Tarek Yousry2,3, Rolf Jager2,3

1MRC Prion Unit, UCL Institute of Neurology, London, UK; 2Academic Neuroradiological Unit, UCL Institute of Neurology, London, UK; 3Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, UK

The purpose of this study was to investigate whether DWI at high b value (b=3000s/mm2) and ADC measurements in the basal nuclei, improve the diagnosis of variant CJD and sporadic CJD compared to DWI at b=1000s/mm2. At high b value, we found that signal change is more conspicuous, improving confidence in the radiological diagnosis of human prion disease. Regional cerebral ADC changes in prion disease patients compared to controls were demonstrated, the anatomical ADC patterns being different in sporadic and variant CJD. Our results suggest that high-b value DWI provides additional pathological sensitivity in prion diseases.

 
Exhibit Hall 2-3                    Wednesday 13:30-15:30          Computer 15

13:30         3345.     Does Obesity Account for Brain Injury in Alcohol Dependent Individuals? – a Multimodal Magnetic Resonance Study at 1.5T.

Stefan Gazdzinski1, Anderson Mon2, Timothy C. Durazzo2, Dieter J. Meyerhoff1,2

1Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA; 2Radiology, University of California, San Francisco, CA, USA

Unhealthy weight is associated with brain structural alterations, lower prefrontal glucose metabolism, and lower N-acetyl-aspartate (NAA, marker of neuronal viability) in healthy individuals. Recent clinical and epidemiological studies suggest higher rates of obesity among alcohol dependent individuals and individuals excessively consuming alcohol. Here, we evaluated whether elevated body mass index (BMI) accounts for brain injury in treated alcoholics abstinent for one month.

14:00         3346.     Assessment of Iron Distribution in Hallevorden-Spatz Syndrome Using Phase Imaging and Relaxation Rate Measurements

Jerzy (Urick) Szumowski1, Susan Hayflick2, Kirsten Gaarder2, Erhan Bas2, Erwin Schwarz2, Deniz Ergogmus2

1Oregon Health Sciences University, Portland, OR, USA; 2OHSU

The aim of this study was to investigate brain iron distribution within the Globus Pallidus in patients with Hallervorden-Spatz Syndrome using phase imaging and relaxation rate measurements.

14:30         3347.     Abnormal Corticostriatal Pathway in Patients with Tourette Syndrome

Rajkumar Munian Govindan1, Malek I. Makki2, Benjamin J. Wilson1, Mike E. Behen3, Harry T. Chugani1

1Pediatrics, Wayne State University, Detroit, Mi, USA; 2Radiology, Wayne State University, Detroit, Mi, USA; 3Psychology, Wayne State University, Detroit, Mi, USA

Many evidences from postmortem and neuroimaging studies have implicated the involvement of fronto-striato-thalamic-cortical (FSTC) circuitry in the involvement of tic generation in children with Tourette Syndrome (TS). In this present study we used track based spatial statistics to identify abnormalities in minor white matter tract changes in 17 children with TS and compared them to 14 age-matched healthy controls. The main findings are increased water diffusivity (ADC) in parts of left external capsule and left subcolosal fasciculus. Furthermore, the mean ADC values measured from EC showed negative correlation with the tic severity score (r = -0.666, p = 0.007).

15:00         3348.     In Vivo 4D Visualization of CSF Flow: Healthy Volunteers and Hydrocephalus

Francesco Santini1, Tilman Schubert2, Klaus Scheffler1, Stephan G. Wetzel2

1Radiological Physics, University of Basel Hospital, Basel, Switzerland; 2Neuroradiology, University of Basel Hospital, Basel, Switzerland

Three-directional time-resolved measurements of cerebro-spinal fluid flow patterns, possible thanks to a custom balanced steady-state free precession phase-contrast sequence, offer new possibilities in the study of diseases like hydrocephalus or Chiari malformation. In this work, flow patterns in the third ventricle acquired in healthy volunteers are compared to a dataset acquired in a patient suffering from a long-standing three-ventricular hydrocephalus. Significant differences are found, and, in the pathological case, the flow measurement proved the existance of an inner shunt through the floor of the third ventricle, not visible by standard anatomical imaging.

 
Exhibit Hall 2-3                    Thursday 13:30-15:30          Computer 15

13:30         3349.     Robust Intensity Normalisation and Automatic Intensity Window Selection for the Calculation of the Boundary Shift Integral

Kelvin Ka-fai Leung1, Matthew Clarkson2, Nick C. Fox2, Sebastien Ourselin1,2

1Centre for Medical Image Computing, University College London, London, UK; 2Dementia Research Centre, University College London, London, UK

The boundary shift integral (BSI) is a robust measure of regional and global cerebral atrophy rates. We describe a new and robust intensity normalisation method to calculate the BSI and applied it to a subset of images from the ADNI database. Initial results show that the new method improves group separation between AD and control groups, with effect size increased from 0.51 to 0.97 as measured by Cohen’s d. This implies that the new method may be more robust to changes in image quality between baseline and repeat scans (e.g. due to scanner upgrade).

14:00         3350.     Use of the Talairach Proportional Grid System for ROI Quantification of Cerebral Blood Volume Maps of the Brain

Santiago Reig1, Juan Adán Guzmán de Villoria2, Javier Olazarán3, Isabel Cruz4, Maria Lacalle5, Eloísa Navarro3, David Ezpeleta3, Jose Maria Mateos5, Verónica García-Vázquez5, Elena Martino5, Manuel Desco5,6

1Centro de investigación en red en salud mental. (CIBERSAM), Madrid, Spain; 2Servicio de Radiodiagnóstico, Hospital General Universitario Gregorio Marañón, Madrid, Spain; 3Servicio de Neurología, Hospital General Universitario Gregorio Marañón, Madrid, Spain; 4Servicio de Neurología, Hospital Infanta Elena, Madrid, Spain; 5Medicina y Cirugía Experimental, Hospital General Universitario Gregorio Marañón, Madrid, Spain; 6Centro de investigación en red en salud mental (CIBERSAM), Madrid, Spain

We present a semiautomatic technique to perform regional quantification of brain Cerebral Blood Volume (CBV) maps obtained by MR Perfusion Weighted Images, using structural MRI images. A Talairach grid system is built on the brain anatomical MRI, and a co-registered CVB map is superimposed on the grid for a regional assessment of brain CVB.

14:30         3351.     Method for Accurate Brain Atrophy Follow-Up Using Functional Relaxometric Classification

J.B.M. Warntjes1,2, J. West1,3, P. Lundberg3

1Center for Medical Imaging Science and Visualization, Linköping, Sweden; 2, Department of Medicine and Health, Division of Clinical Physiology, Linköping, Sweden; 3Department of Medicine and Health, Division of Radiation Physics, Linköping, Sweden

Accurate estimations for white matter, grey matter and cerebro-spinal fluid volumes can be retrieved from Quantitative Magnetic Resonance Imaging data by creating a multi-parametric space for Functional Relaxometric Classification (‘FRC-space’). Since each tissue has a unique combination of MR parameters it will form a cluster in the FRC-space, characterized by its position and its statistical distribution. If an image-voxel contains two tissue types, it has coordinates in between the cluster positions of the separate tissues. Hence an estimation of tissue probability can be retrieved geometrically from FRC-space. Brain volumes of elderly were compared to a group of young volunteers.

15:00         3352.     Dynamic Contrast Enhanced MRI for Investigation of the Blood-Brain Barrier in an Experimental Model of Communicating Hydrocephalus

Laura Fanea1, Shams Rashid1, James P II McAllister2, Jie Li3, Helene Benveniste4, Mei Yu4, Mark E. Wagshul1

1Department of Radiology, SUNY Stony Brook, Stony Brook, NY, USA; 2Division of Pediatric Neurosurgery, Primary Children's Hospital, University of Utah, Salt Lake City, UT, USA; 3Department of Pediatric Neurosurgery, Children's Hospital of Michigan, Detroit, MI, USA; 4Medical Department, Brookhaven National Laboratory, Upton, NY, USA

Hydrocephalus (HC) represents the leading cause for brain surgery in children in the US. While treatment of HC with ventriculoperitoneal shunting is a well established technique with marked improvement in patient outcome, there are still numerous complications and the mean lifetime of a shunt before needing revision surgery is only a little over one year. The disruption of normal CSF flow and drainage in hydrocephalus is assumed to be the primary “pathology” of this disease and thus the reestablishment of CSF drainage with the shunt is the logical treatment of choice. However, with the complications associated with shunting and the lack of a clear understanding of the source of CSF blockage in many cases it may be beneficial to study other aspects of the disease. For example, it is well established that there are alterations in cerebral blood flow patterns in the brain in hydrocephalus.