872.       Particle Embedded Culture Dishes for Magnetic Cell Labeling

Dorit Granot¹, Erik M. Shapiro^1,2

¹Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA; ²Department of Biomedical Engineering, Yale University, New Haven, CT, USA

We demonstrate a potentially standardized, sterile, reproducible and stand alone new method for magnetic cell labeling. The basic idea is a plastic cell culture dish coated with various biopolymers commonly used in cell culture in which magnetic nano- or microparticles are embedded. Adherent cells are plated on the dish, and upon attachment endocytose particles directly off the dish. As many cell types require culture either as a step in their purification, a culture vessel which includes the magnetic cell labeling step could prove useful in accelerating cell labeling times and ease, particularly in clinical environments.

                  873.       Intracellular MRI Contrast by SPIOs and Dy Chelates at 11.75 and 21.1 T

Jens Thorvald Rosenberg^1,2, Joshua M. Kogot³, Chris Ridel³, Geoffery F. Strouse³, Samuel C. Grant^1,2

¹The National High Magnetic Field Laboratory, Tallahassee, FL, USA; ²Chemical and Biomedical Engineering, Florida State University, Tallahassee, FL, USA; ³Chemistry and Biochemistry, Florida State University, Tallahassee, FL, USA

We have compared intracellular SPIOs in murine microglia cells (Bv-2) at two field strengths, 11.75 and 21.1 T. Cells incubated with SPIOs were immobilized in 1% agarose layers for imaging. T1, T2 and T2* were assessed. Two experimental variables were tested, agent dosing and cell count. Agent dosing showed no difference between field strengths while variations in the cell count did display field-related effects. Dy-DOTA and Dy-DTPA were also evaluated. Dy-DOTA showed increased uptake, possibly due to the more positively charged DOTA molecule. These findings impact the choice of contrast agent for high field studies of implanted cell lines.

                  874.       Simplified Synthesis and Characterization of Magnetoferritin for Convection Enhanced Delivery

Veronica Clavijo Jordan¹, Michael R. Caplan¹, Kevin M. Bennett¹

¹Harrington Department of Bioengineering, Arizona State University, Tempe, Az, USA

Convection-enhanced delivery has been proposed to deliver agents with very high specificity to the brain to detect malignant tumors, but the technique requires high-relaxivity agents for detection. Because these agents must be delivered by convection, they must also have size ranges similar to biological molecules. Here we developed a procedure to synthesize magnetoferritin from commercially-available apoferritin, with a 96-fold increase in relaxivity over native ferritin. The nanoparticles were made monodisperse and the protein’s perfusion characteristics were compared to targeting peptides intended for CED. This makes it practical to use magnetoferritin for CED to detect malignant glioma cells with MRI.

                  875.       Early Detection of Sepsis by Quantifying SPIO Uptake by LPS-Activated Macrophages Using COSMOS

Richard Wong^1,2, Tian Liu^1,2, Jian Shou³, Philip S. Barie³, Yi Wang^1,2

¹Biomedical Engineering, Cornell University, Ithaca, NY, USA; ²Department of Radiology, Cornell University - Weill Medical College, New York, NY, USA; ³Department of Surgery, New York-Presbyterian Hospital - Weill Cornell Medical Center, New York, NY, USA

This study offers an in vitro proof of concept; RAW264.7 murine monocytes were treated with lipopolysaccharide to induce a sepsis-like cell condition, were incubated with the FDA-approved contrast agent Feridex IV, and were imaged using the COSMOS technique (Calculation of Susceptibility through Multiple Orientation Sampling) for the quantification of iron. Results indicate that statistically significant differences can be found in SPIO uptake between activiated and control cells, indicating a potential use for COSMOS in the in vivo diagnosis of sepsis.

                  876.       In Vivo Tracking of Biomaterial Degradation of Hydrogels Synthesized with Protein Polymer-Based Contrast Agents

Emily Alexandria Waters¹, Lindsay Karfeld-Sulzer², Ellen Kohlmeir³, Hermann Kissler⁴, Xiaomin Zhang⁴, Dixon Kaufman⁴, Annelise Barron^1,2, Thomas Meade^1,3

¹Chemistry, Northwestern University, Evanston, IL, USA; ²Chemical and Biological Engineering, Northwestern University, Evanston, IL, USA; ³Biochemistry, Molecular and Cell Biology, Northwestern University, Evanston, IL, USA; ⁴Transplant Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Biomaterial scaffolds are employed for controlled-release drug delivery and as extracellular matrices to support cellular therapies, but are difficult to track over time. Biomaterial scaffolds with covalently incorporated T1-shortening agents could improve contrast with surrounding tissues. We have developed artificial protein polymers generated by recombinant protein expression in E. Coli. These proteins have evenly spaced lysine residues which can be modified with Gd(III) chelators and enzymatically cross-linked into hydrogels. The relaxivity can be tuned by varying the lysine spacing and number of repeats in the polymer. We demonstrate in vivo MRI tracking of degradation of a hydrogel containing these polymers.

                  877.       About the Origins of Enhanced Visualization of Amyloid Plaques on APP/PS1 Mouse Brain Using GdDOTA Passive Staining

Benjamin Marty¹, Julien Flament¹, Julien Valette¹, Fawzi Boumezbeur¹, Marc Dhenain¹, Franck Lethimonnier¹, Sébastien Mériaux¹

¹Neurospin, I2BM, Commisariat à l'Energie Atomique, Gif-sur-Yvette, France

The present study shows the interest of passive staining and T2* weighted images to detect amyloid plaques on a APP/PS1 mouse brain. It also focus on the diffusion of contrast agent during this experiment and the consequences on the contrast of images. It shows that an important contrast in proton density appears added to the existent T2* contrast.

                  878.       Equilibrium and Kinetic Properties of  Gd(III)AAZTA Complex a Highly Efficient MRI Contrast Agent

Fulvio Uggeri¹, Alessandro Maiocchi¹, Silvio Aime², Erno Brucher³, Zsolt Baranyai³, Attila Benyei³

¹Bracco Imaging s.p.a., Colleretto Giacosa, Torino, Italy; ²Università degli Studi di Torino, Torino, Italy; ³University of Debrecen, Debrecen, Hungary

The heptadentate ligand AAZTA and its derivatives were recently reported to give stable complexes with Gd(III) with superior efficiency as MRI contrast agents. Nevertheless, only preliminary data are available on the coordination behaviour of this interesting ligand. In this work, thermodynamic and kinetic stability data are determined for the complex formation of AAZTA towards Gd(III) ions and other metal ion of interest for this application. The obtained data have shown that near physiological conditions Gd(AAZTA) is significantly more inert than Gd(DTPA)allowing its potentially safe use as contrast agent in MRI.

                  879.       New Family of Dendrimeric Ligands as MRI Contrast Agents

Jesus Pacheco-Torres¹, Francisco Fernández-Trillo², Eduardo Fernández-Megía², Ricardo J. Riguera², Paloma Ballesteros³, Pilar Lopez-Larrubia⁴, Sebastian Cerdan⁴

¹Instituto de Investigaciones Biomédicas "Alberto Sols" - CSIC , Madrid, Spain; ²Universidad de Santiago de Compostela, Santiago de Compostela, Spain; ³Instituto Universitario de Investigación - UNED, Madrid, Spain; ⁴Instituto de Investigaciones Biomédicas "Alberto Sols" - CSIC, Madrid, Spain

Although Magnetic Resonance Imaging methods inherently provide high intrinsic tissue contrast, the use of extrinsic contrast agents (CA's) has become a routine in many diagnostic imaging procedures. The paramagnetic lanthanide Gd(III) is used to increase locally the longitudinal relaxation rate of surrounding tissue water, highlighting the intensity of specific tissue areas in T₁-weighted images. In this work we analyze the ability of a new family of Gd chelating derivatives to be used as CA's. Relaxivity measurements were made at clinical and high field showing a clear improvement in the relaxation properties of these structures related to those usually employed.

                  880.       Nanocontrast Agents for In Vivo Probing on Non-Small Cell Lung Cancer in MR Molecular Imaging

Ching-Tang Chen¹, Chia-Hao Su¹, Yi-Chien Lu¹, Ang Yuan², Jyh-Horng Chen¹

¹Interdisciplinary MRI/MRS Lab, Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan, Taiwan; ²Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Taiwan

We have demonstrated that Fe₃O₄@anti-EGFR antibody nanoparticles were capable of probing NSCLC cells in vitro and in vivo. Furthermore, its large different expression between NSCLC cells and monocyte provide nanoparticles higher chance to target the extracellular domain of EGF receptors in tumor cells. And we also have investigated the biodistribution, and kinetics of the nanoparticles. By recombining the desired targeting moiety and various functional nanoparticles through bioconjugation, this modularly designed platform has the capability of enhancing the efficiency of targeted diagnosis and therapies for a wide spectrum of biomedical applications.

                  881.       Cardiac Magnetic Resonance  to Detect Cell Death in Vivo

Rajesh Dash^1,2, Trevor Chan², Mayumi Yamada², Marietta Paningbatan^1,3, Philip Swigart^1,3, Bat-Erdene Myagmar¹, Paul C. Simpson^1,3, Phillip C. Yang²

¹Medicine, UCSF, San Francisco, CA, USA; ²Medicine, Stanford University, Stanford, CA, USA; ³San Francisco VAMC

Early, non-invasive detection of cell death in ischemic and non-ischemic cardiomyopathy could play a critical role in expanding therapeutic options. Purified Annexin V (ANX) protein was labeled with superparamagnetic iron oxide nanoparticles (SPIO), and this conjugate compound was previously shown to bind to apoptotic cardiomyocytes in culture with high specificity and sensitivity. In this study, systemically-delivered ANX-SPIO is detectable by T2 cardiac MRI in the myocardium following ischemic and oxidative insults. These results suggest that future non-invasive, longitudinal monitoring of cardiac cell death is possible using MRI and magnetic contrast particle labeling.

                  882.       Contrast Enhanced MR Imaging of Liver Tumors in HBV Transgenic Mice

Vito Lorusso¹, Luigi Miragoli¹, Linda Chaabane², Achille Iolascon³, Daniela Spano³, Vittorio Di Maso⁴, Claudio Tiribelli⁴, Fulvio Uggeri¹

¹Bracco Research Centre, Bracco Imaging spa, Colleretto Giacosa, Torino, Italy; ²RBM-Merk-Serono, Colleretto Giacosa, Torino, Italy; ³CEINGE, Napoli, Italy; ⁴Centro Studi Fegato, Trieste, Italy

In the HBx transgenic mouse model chronic hepatocellular injury and inflammation lead to regenerative hyperplasia and to the development of hepatocellular carcinoma thereby resembling many of the physiopathological events that occur prior to the development of HCC in chronic HBV infection in humans.

                  883.       Quantitative 3D Molecular Imaging of Kidney Glomeruli

David H. Frakes¹, Arius Elvikis², Jonathan Plasencia¹, Scott Beeman¹, Kevin M. Bennett¹

¹Harrington Department of Bioengineering, Arizona State University, Tempe, Az, USA; ²Partnership for Research in Spatial modeling, Arizona State University, Tempe, Az, USA

Cationic iron oxide nanoparticles bind with high specificity to anionic glycosaminoglycans in renal glomerular. The accumulation of these nanoparticles is detectable with MRI, giving images of agent uptake by individual glomeruli. In this work, we developed a technique to quantify the number of glomeruli in a rat kidney based on 3D MR image after cationic agent injection . The number of glomeruli counted here is consistent with the known number of glomeruli. The technique is thus proposed to quantify glomerular structure and function in vivo, and may be useful for detecting the distribution of contrast agents throughout the body.

                  884.       Early in Vivo Manganese-Enhanced MRI (MEMRI) Detection of Embryonic Stem Cell Induced Teratoma Formation

Jaehoon Chung¹, Joelle K. Barral², Irv Weissman³, robert c. robbins⁴, Phillip C. Yang¹

¹Cardiovasclar Medicine, Stanford University, Stanford, CA, USA; ²Electrical engineering, Stanford University, Stanford, CA, USA; ³Pathology, Stanford University, Stanford, CA, USA; ⁴cardiothoracic surgery, Stanford University, Stanford, CA, USA

MEMRI can detect embryonic stem cell induced teratoma at an early stage.

                  885.       Characterization of Single Wall Carbon Nanotubes as Anysotropic Contrast Agents for MRI

Pilar Lopez-Larrubia¹, Viviana Negri², Laura Nieto-Charques¹, Sebastian Cerdan¹, Paloma Ballesteros²

¹Biomedical Research Institute, Madrid, Spain; ²Universidad Nacional de Educación a Distancia

The increased use of Magnetic Resonance Imaging methods as clinical diagnostic tools has prompted for the development of new, more powerful and selective MRI contrast agents (CAs). Our research group has prepared and characterized new paramagnetic CAs and pH probes aimed to measure the extracellular pH within tumours through ¹H MRSI. In this work our aim is to develop a new generation of paramagnetic CAs with anisotropic magnetic properties, being the Single Wall Carbon Nanotubes the ideal systems. We propose the use of these materials to distinguish between laminar or turbulent flow in the normal or pathologic biological systems.

                  886.       Detection and Characterization of Europium Based PARACEST Contrast Agents

Heather H. Cornnell¹, Arthur S. Edison^2,3, Glenn A. Walter^3,4

¹Biomedical Engineering, University of Florida, Gainesville, FL, USA; ²Biochemistry & Molecular Biology, University of Florida, Gainesville, FL, USA; ³National High Magnetic Field Laboratory, University of Florida, FL, USA; ⁴4Physiology and Functional Genomics, University of Florida, Gainesville, FL, USA

Paramagnetic Chemical Exchange Saturation Transfer (PARACEST) utilizes an RF pulse to saturate a small pool of bound protons at the chemical shift induced by the paramagnetic lanthanide complexes. Exchange between this saturated proton pool and free protons in bulk water results in decreased signal from bulk water. Sensitivity to small concentrations of PARACEST agent would be useful to increase the potential for this mode of contrast generation. This abstract investigates the detection of a europium based PARACEST agent from 100mM down to 0.4mM. The results demonstrate contrast generation at 14.6T for various pH’s and temperatures.

                  887.       Synthesis, Characterization and Application of Citrate Modified Superparamagetic Iron Oxide Nanoaparticles as a New Contrast Agent for Magnetic Resonance Imaging

Sachchidanand Srivastava¹, Rishi Awasthi², Namdeo Sri Ram Gajbhiye¹, Vikas Agarwal³, Amit Singh³, Rakesh K. Gupta

¹Department of Chemistry, Indian Institute of Technology, Kanpur, Uttar Pradesh, India; ²Department of Radiodiagnosis, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India; ³Department of Immunology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

The synthesis of monodispersive citrate coated Fe3O4 magnetic nanoparticle was done by high temperature co-precipitation method using diethyl glycol as solvent. The nanoparticle was characterized by Powder X-ray Diffraction (XRD), transmission electron microscopy (TEM), Fourier Transform Infra Red (FTIR) and Vibrational Sample Magnetometer (VSM). Cellular uptake of magnetic nanoparticles was found to be 90-95% in RAW cell line and 20-30% in jurket cell line. Jurket cell line being non-phagocytic, showed less uptake of magnetic nanoparticles, but the uptake may indicate the nonspecific engulfment of these nanoparticles. On T2*GRE sequence the labeled cells showed strong T2* effect. We conclude that the electrostatic stabilization allows the production of much smaller nano particles than conventional USPIO and on proper optimization these nanoparticles may be used as MR contrast agent.

                  888.       Novel Two Step PAMAM Dendrimers for Targeted MRI of TfR Expression

Cesar A. Berrios-Otero¹, Steven Isaacman², Ben B. Bartelle¹, Kamila U. Szulc¹, James Canary², Daniel H. Turnbull^1,3

¹Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, NYU School of Medicine, New York, USA; ²Chemistry, New York University, New York, USA; ³Radiology, NYU School of Medicine, New York, USA

Paramagnetic contrast agents targeted to cell membrane receptors are currently of great interest for molecular imaging with MRI. In addition to the advantages of imaging endogenous receptors, receptor targeted MRI has also been proposed as a method for imaging transgene expression. Previous studies have used gadolinium chelates as T1-agents for targeting. One limitation of current targeting methods, especially with T1-agents, is the low sensitivity for detection, suggesting the need for more effective amplification schemes. Here we have tested a two-step strategy based on PAMAM dendrimers, with the primary dendrimer targeted to Transferrin Receptor, and the secondary dendrimer containing up to 50 Gd-DTPA molecules for amplification of the T1 relaxation effects.

                  889.       REACTION: Release Activation of Iron Oxide Nanoparticles: A Novel Environmentally Sensitive MRI Paradigm

Dorit Granot¹, Erik M. Shapiro^1,2

¹Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA; ²Department of Biomedical Engineering, Yale University, New Haven, CT, USA

We report a new enzyme/contrast agent paradigm which achieves enzymatically responsive changes in relaxation times of magnetically labeled cells. Cells are labeled with biopolymer-coated particles which are cleavable by a specific enzyme. This coating restricts the approach of water to the particles, preventing the magnetic core from relaxing protons. The reactive enzyme potentially can be engineered as a reporter protein, whose expression can be regulated. The enzyme cleaves the particle coating, releasing the magnetic center, increasing the relaxivity of the agent. We demonstrate the principal of enzyme-mediated changes in nanoparticle relaxivity in cell free assays, in-cellulo, and in-vivo in animals.

                  890.       Using  MagA and Modified Ferritin Subunits to Track Tumor Cell Growth

Donna E. Goldhawk¹, Rene Figueredo², Claude Lemaire³, Paula Foster⁴, Savita Dhanvantari⁵, Jim Koropatnick², R Terry Thompson¹, Frank S. Prato¹

¹Imaging, Lawson Health Research Institute, London, ON, Canada; ²London Regional Cancer Program, London, ON, Canada; ³Physics and Astronomy, University of Waterloo, Waterloo, ON, Canada; ⁴Imaging, Robarts Research Insitute, London, ON, Canada; ⁵Diabetes and Metabolism, Lawson Health Research Institute, London, ON, Canada

We have investigated the application of gene-based contrast from overexpression of iron binding proteins, in tracking cancer cell growth using MRI. Here we compare expression of modified ferritin subunits (HF+LF), lacking iron response elements (1), with that of MagA, an iron transporter from magnetotactic bacteria (2), in a preclinical model of human cancer. These studies describe the relative potential of engineered tumor cells to differentiate in vivo and provide suitable contrast for MRI.

                  891.       Combined Imaging and Delivery of SiRNA to Pancreatic Islets

Zdravka Medarova¹, Mohanraja Kumar¹, Shu-wing Ng², Junzheng Yang², Natasha Barteneva³, Natalia Evgenov¹, Victoria Petkova⁴, Anna Moore¹

¹MGH/HST Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA; ²Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, MA, USA; ³Immune Disease Institute and Department of Pathology, Harvard Medical School, Boston, MA, USA; ⁴Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA

A powerful new approach for the directed regulation of gene expression utilizes the phenomenon of RNA interference. Here, we establish the feasibility of a novel technology centered around multifunctional magnetic nanocarriers (MN-NIRF-siRNA), which concurrently deliver siRNA to intact pancreatic islets and can be detected by magnetic resonance (MRI) and optical imaging. MN-NIRF-siRNA consists of superparamagnetic iron oxide nanoparticles (for magnetic resonance imaging), labeled with Cy5.5 dye (for near-infrared optical imaging), and conjugated to a DY547-labeled synthetic siRNA duplex targeting a model gene. Probe accumulation in the islets could be visualized by MRI and optical imaging. It resulted in a significant reduction in target gene expression levels. Our studies establish the feasibility of nanoparticle-based image-tagged siRNA delivery to pancreatic islets, using a novel multifunctional probe, which, in addition to its capability to deliver gene therapy in the form of siRNA, can also serve as an imaging contrast agent capable of detecting and following the fate of the probe in pancreatic islets.

                  892.       Synthesis and Characterization of Novel Triple-Layer Nanoparticles with Multimodal Potential-First Results

Zdravka Medarova¹, Mehmet Yigit¹, Chongzhao Ran¹, Mohanraja Kumar¹, Anna Moore¹

¹MGH/HST Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA

We have synthesized a nanoparticulate contrast agent that consists of elements detectable by computed tomography (CT), magnetic resonance imaging (MRI) and optical imaging (Raman microscopy) without the addition of ligands, such as optical dyes, paramagnetic ions, or iodine. The contrast agent (AuruMN) represents a three-layer construct, consisting of a 3-5 nm core of iron oxide (detectable by MRI), covered with dextran-T10 for a resulting diameter of ~30 nm, and coated with gold (compatible with detection by CT and Raman microscopy) for a final diameter of ~70 nm. The nanoparticle preparation described here can find application in pre-clinical and clinical diagnostics and therapy. It represents a versatile platform based on which one can design a wealth of diagnostic/therapeutic agents through functionalization of the nanoparticles with targeting moieties, specific for chosen cells, tissues, or biological processes as well as with molecular therapeutic agents.

                  893.       In Vivo Detection of Lymphatic Delivery of Liposomes Using DIACEST MRI Labeling

Guanshu Liu^1,2, Yah-el Har-el², Chris Long³, Assaf A. Gilad^2,4, George Sgouros², Jeff W.M. Bulte^2,4, Peter C.M. van Zijl^1,2, Michael T. McMahon^1,2

¹F.M. Kirby Center, Kennedy Krieger Institute, Baltimore, MD, USA; ²Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; ³Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD; ⁴Institute for Cellular Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

In order to facilitate the noninvasive detection of lymphatic delivery of anticancer drugs, we developed a new MRI-visible liposome system based on labeling with the diamagnetic Chemical Exchange Saturation Transfer (DIACEST) agent L-arginine. Using B0-corrected CEST-MRI, the accumulation of liposome in the popliteal lymph node could be visualized in vivo in mice (n = 3). To validate the approach, liposomes were simultaneously labeled with a fluorescent chromophore, the fluorescence of which correlated with the CEST intensity. This new DIACEST liposome system allows direct visualization of drug delivery to the lymph nodes without using paramagnetic material.

                  894.       Multimodal Thermo-Sensitive Polymer-Modified Liposome for Visualization and Treatment of Disseminated Cancer

Daisuke Kokuryo¹, Hiroyuki Yoshida², Kenji Kono², Iwao Kanno¹, Ichio Aoki¹

¹Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; ²Graduate School of Engineering, Osaka Prefecture University, Sakai, Japan

A drug delivery system using a multimodal thermo-sensitive 'polymer-modified' liposome (MTPL) would be a powerful imaging tool to help avoid the side-effects of chemotherapy on the intact organ. In this study, an accumulation of and thermo-triggered drug release from MTPL were evaluated for disseminated-cancer using MRI and optical imaging. In the ex vivo optical images, the MTPL accumulation in the tumor area increased over 8 hours after the administration. In the T₁-weighted MRI, the signal intensities in the bowel and the kidney changed after thermo-triggering.

                  895.       Comparison of Neutral and Charged High Density Lipoprotein Using Bimodal Nanoparticles

Torjus Skajaa^1,2, Stefanie Jacoba Cornelia Geertruda Hectors¹, David P. Cormode¹, Nazila Kamaly³, Andrew D. Miller^3,4, Wei Chen¹, Alessandra Barazza⁵, Edward A. Fisher⁵, 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; ³Department of Chemistry, Genetic Therapies Centre, Imperial College, London, UK; ⁴Hammersmith Hospital, London, UK; ⁵School of Medicine, New York University, New York, NY, USA

We here present a comparison between neutral and charged HDL like bimodal contrast agents. The particles were extensively characterized, applied on macrophages cells in vitro and on apoE-KO mice in vivo which were imaged with optical and magnetic resonance imaging.

                  896.       Molecular MRI and Fluorescence Imaging of Atherosclerosis Using Annexin A5-Functionalized Bimodal Nanoparticles

Geralda A.F. van Tilborg¹, Esad Vucic², Gustav J. Strijkers¹, David P. Cormode², Venkatesh Mani², Torjus Skajaa², Chris P.M. Reutelingsperger³, Zahi A. Fayad², Willem J.M. Mulder², Klaas Nicolay¹

¹Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands; ²Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, NY, USA; ³Cardiovascular Research Institute Maastricht, Department of Biochemistry, Maastricht University, Maastricht, Netherlands

Apoptosis and macrophage burden are believed to correlate with plaque vulnerability. In the present study, we investigated the use of a small annexin A5-functionalized bimodal micellar contrast agent for non-invasive magnetic resonance imaging (MRI) of macrophages and/or apoptotic cells in atherosclerotic lesions of apoE-/- mice. In vivo MRI of the abdominal aorta and ex vivo near-infrared fluorescence imaging of whole aortas revealed an elevated uptake of the annexin A5-micelles compared to untargeted control-micelles. Ex vivo immunofluorescence images of cryosections confirmed binding of the annexin A5-micelles to macrophages and apoptotic cells.

                  897.       A Macrophage Specific Nanoparticle Suitable for Magnetic Resonance, Fluorescence, and Magnetic Particle Imaging

Willem J.M. Mulder¹, Torjus Skajaa^1,2, David P. Cormode¹, Hans Boeve³, Zahi A. Fayad¹

¹Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, NY, USA; ²Faculty of Health Sciences, Aarhus, Denmark; ³Philips Research Laboratories, Eindhoven, Netherlands

Magnetic particle imaging (MPI) is a new imaging technique that has advantages for cardiac imaging. Here we present an iron oxide nanoparticle that is similar to high density lipoprotein (FeO-HDL) and can provide contrast for MRI, fluorescence techniques and MPI. We show macrophage cells to avidly take up FeO-HDL using these three imaging modalities, thereby indicating the potential of these nanoparticles in cardiovascular settings, in particular for MPI.

                  898.       New Fluorinated Gd-AspGlyMe-DOTA Complexes for ¹⁹F-MRI

Markus Plaumann¹, Ekkehard Küstermann², Dieter Leibfritz¹

¹Institute of Organic Chemistry, University of Bremen, Bremen, Germany; ²CAI, MRI/MRS, University of Bremen, Bremen, Germany

Fluorine is of interest in medical chemistry and diagnostics, because of its very low natural abundance in living organisms and high MR sensitivity. Fluorinated contrast agents allow to record ¹⁹F-images without any background signals and additional classical ¹H-MR imaging at the same time. Two 3,5-Bis(trifluoromethyl)benzyl derivatives were selected as model compounds to compare ten different Gd³⁺-DTPA-, Gd³⁺-GlyMe-DOTA- and Gd³⁺-AspGlyMe-DOTA complexes with respect to their lipophilicity and T₁-times. MRI experiments of selective molecules and ICP-MS measurements proof the possibility to label rat glioma C6 cells.

                 899.       Phase Gradient Mapping (PGM) for Positive Contrast Generation

Sunbok Lee¹, Jason Langley¹, Wei Liu², Qun Zhao^1,3

¹Physics and Astronomy, University of Georgia, Athens, GA, USA; ²Philips research North America, Briarcliff, NY, USA; ³BioImaging Research Center, University of Georgia, Athens, GA, USA

In vivo detection of superparamagnetic iron oxide (SPIO) contrast agent can be used in many applications such as cell tracking. In this study a new post-processing method, referred to as PGM (Phase Gradient Mapping) is proposed to obtain a positive contrast image. This method measures the derivative of a phase map to detect the field inhomogeneity induced by the SIPO’s susceptibility gradient. The PGM results from a phantom dataset and in vivo mouse dataset show positive contrast generated around SPIO.

                  900.       In Vivo Off Resonance Saturation Magnetic Resonance Imaging of  α _vβ ₃-Targeted Superparamagnetic Nanoparticles

Chalermchai Khemtong¹, Chase W. Kessinger¹, Jimin Ren², Erik A. Bey¹, Su-Geun Yang¹, Jagadeesh Setti Guthi¹, David A. Boothman¹, A Dean Sherry², Jinming Gao¹

¹Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; ²The Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA

Magnetic resonance imaging (MRI) is a powerful clinical imaging technique that allows for non-invasive tomographic visualization of anatomic structures with high spatial resolution and soft tissue contrast. However, its application in molecular imaging of cancer has been limited by the lack of sensitivity and detection accuracy in depicting the biochemical expression of these diseases. Here, we combine an ultra-sensitive design of superparamagnetic polymeric micelles (SPPM) and an off-resonance saturation (ORS) method to enhance the imaging efficacy of tumor biomarkers in vivo. SPPM nanoparticles encoded with cyclic(RGDfK) were able to target the αvβ3-expressing microvasculature in A549 non-small cell lung tumor xenografts in mice. ORS greatly improved tumor detection accuracy over the conventional T2*-w method by its ability to turn “ON” the contrast of SPPM. This combination of ORS imaging with a tumor vasculature-targeted, ultra-sensitive SPPM design offers new opportunities in molecular imaging of cancer.

                  901.       Quantitative Ocular Pharmacokinetics Study in Rabbit Using T1 Mapping

Xianfeng Shi¹, Xin Liu², Xueming Wu³, Zhengrong Lu⁴, Kevin Li⁵, EunKee Jeong⁶

¹Department of Physics, University of utah, Salt Lake City, UT, USA; ²Department of physics, University of Utah, Salt Lake City, UT, USA; ³Department of  Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA; ⁴Department of  Pharmaceutics and Pharmaceutical Chemistry, University of utah, Salt Lake City, UT, USA; ⁵Division of Pharmaceutical Sciences, University of Cincinnati, Salt Lake City, UT, USA; ⁶Department of Radiology, University of utah, Salt Lake City, UT, USA

Recent advances in drug discovery have led to the development of effective therapeutic agents for the treatment of posterior eye diseases. However, drug delivery to the posterior eye remains a challenge and intravitreal injection continues to be the most common method in ocular drug delivery to the back of the eye. The use of MRI to study the distribution of biodegradable synthetic polymer in the eye would help us understand the ocular drug-delivery mechanism and clearance after intravitreal injection. In this report, we present an MRI study of polymerized biodegradable drug surrogate conjugated with Gd-chelate that was injected into the rabbit eye.

                  902.       Estimating Amounts of Iron Oxide from Gradient Echo Images

W Thomas Dixon¹, Daniel J. Blezek², Lisa A. Lowery¹, Dan E. Meyer¹, Amit M. Kulkarni¹, Brian C. Bales¹, Danielle L. Petko¹, Thomas K. Foo¹

¹GE Global Research, Niskayuna, NY, USA; ²Mayo Clinic, Rochester, MN, USA

Rat legs directly injected with SPIO provided a test of iron measurements based on dual gradient-echo images. We fitted three ways to a point dipole field model, fitting the amount of iron to the volume blackened by intravoxel phase difference, fitting to the phase pattern of either echo, and fitting to the difference in phase between the 1st and 2nd echoes. Following a 3 microgram injection, the latter method gave 2.48±0.26 microgram std following 18 independent measurements. Iron free control regions gave -90 and -140 nanogram estimates. The other methods were much less accurate and were artifactually orientation dependent.

                  903.       In Vivo Assessment of the Number of Iron-Labeled Cells Using T2 Quantification

Jean-Christophe Brisset^1,2, Virginie Desestret^1,2, Sebastien Marcellino^1,3, Emilie Devillard^1,4, Fabien Chauveau^1,2, Florence Lagarde^1,3, Serge Nataf^1,4, Norbert Nighoghossian^1,2, Yves Berthezene^1,2, Marlene Wiart^1,2

¹University of Lyon, Lyon, France; ²CNRS, UMR 5220; Inserm, U 630; Insa de Lyon; Creatis-LRMN, lyon, France; ³CNRS, UMR 5180; Laboratoire des Sciences Analytiques, villeurbanne, France; ⁴Inserm U842; NeuroOncologie and NeuroInflammation, lyon, France

The purpose of our study was to test the hypothesis that T2 quantification could be used in vivo to estimate the number of iron-labeled cells into the brain. Macrophages were incubated in the presence of Ferumoxtran-10 or anionic nanoparticles AMNP and stereotaxically injected in the striatum of mice. MRI was performed at 7T using multi-slice multi-echo imaging for T2 quantification. There was an overall fair agreement between the number of injected cells and the number of cells estimated from T2 measurements. Further studies are needed to assess the potential of this approach to estimate small number of cells.

                  904.       Dual Contrast Method for Cellular MRI Using Positive and Negative Contrast Agents

Young Beom Kim^1,2, Seung-Schik Yoo³, Ki Hyun Bae⁴, Tae Gwan Park⁴, HyunWook Park¹

¹Electrical Engineering, KAIST, Daejeon, Korea; ²In-Vivo-NMR Laboratory, Max-Planck-Institute for Neurological Research, Cologne, Germany; ³Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; ⁴Biological Sciences, KAIST, Daejeon, Korea

MR contrast agents (CAs) are important elements in the cellular MRI for labeling the cells to be visualized. Gadolinium (Gd) chelates are used for T1-weighted imaging and produce a signal increase, and superparamagnetic iron oxide particles (SPIOs) produce T2-weighted signal reduction. Although SPIOs provide more contrast than Gd-chelates, the negative contrast can be confused with signal voids from tissue inhomogeneity, edema, or local hemorrhage. We examined the utility of using combination of these two CAs in MRI for concurrent cell-labeling and dual contrast visualization.

                  905.       Gadonanotubes as a Dual Modal T₁ and T₂^* MRI Contrast Agent: Magnetic Property Characterization by SQUID Magnetometry

Michael L. Matson¹, Lon J. Wilson¹

¹Department of Chemistry, Rice University, Houston, TX, USA

Ultra-short, single-walled carbon nanotube capsules (US-tubes) internalized with aqueous gadolinium-ion clusters (Gadonanotubes) are a dual modal MRI contrast agent capable of decreasing both T1 and T2*. The magnetic properties of both the empty, US-tube nanocapsules and the Gadonanotubes were measured via SQUID magnetometry. The results suggest the empty US-tube nanocapsules have a superparamagnetic domain, while the internalized aqueous Gd3+-ion clusters of the Gadonanotubes posses a separate paramagnetic domain. These two domains together allow for significant shortening of both T1 and T2*.

                  906.       Detection Limits of Very Small Iron Oxide Nanoparticles in Labeled Cells: A Quantitative Evaluation of Histochemistry and MR-Relaxometry

Gert Klug¹, Johannes Bremicker¹, Thomas Kampf², Elisabeth Bauer¹, Thomas Basse-Lüsebrink², Meike Weber³, Uwe Gbureck⁴, Ulrich Nöth³, Peter Michael Jakob², Wolfgang Rudolf Bauer¹

¹Medizinische Klinik und Poliklinik I, Universitätsklinikum Würzburg, Würzburg, Germany; ²Experimentelle Physik 5, Universität Würzburg, Würzburg, Germany; ³Orthopädisches Zentrum für Muskuloskelettale Forschung, Orthopädische Klinik König-Ludwig Haus, Würzburg, Germany; ⁴Abteilung für Funktionswerkstoffe der Medizin und der Zahnheilkunde, Universitätsklinikum Würzburg, Würzburg, Germany

With regard to the growing interest in MR-cell-tracking based on ION-labeled cells a determination of detection limits of IONs by means of MRI and histochemistry remains crucial. We investigated the relation between intracellular iron content (pg/cell) and the capability of histochemistry and MRI to detect in vitro ION-labeled cells. We have shown that MRI is able to detect even low amounts of intracellular VSOP that histochemistry fails to detect. Our results suggest that for the histological validation of MR-cell-tracking studies with VSOP at least 2.13 pg/cell should be achieved.

                  907.       R₂* Quantification of High Iron Concentrations for Cellular Therapy Applications with TurboSPI

James A. Rioux^1,2, Steven D. Beyea^2,3, Chris V. Bowen^2,3

¹Department of Physics, Dalhousie University, Halifax, NS, Canada; ²National Research Council - Institute for Biodiagnostics (Atlantic), Halifax, NS, Canada; ³Departments of Physics, Radiology and Biomedical Engineering, Dalhousie University, Halifax, NS, Canada

The evaluation of cellular therapies with MRI requires techniques which can quantitatively image cell populations labelled with high concentrations of iron oxide. We are exploring the use of TurboSPI, an accelerated single point imaging method, to quantitatively measure R₂*, which can be related to cellular density and iron content. TurboSPI images retain signal from high R₂* regions, and can quantify R₂* over a range inaccessible to tradtional techniques. For MPIO particles, R₂* up to 600 s^-1 can be quantified, corresponding to an iron concentration of 28 ug/mL. For SPIO compartmentalized in cells, TurboSPI should permit quantification up to R₂* of 3000 s^-1 or higher.

                  908.       Direct Detection of SPIO Labeled Stem Cells

Martin Andreas Rückert¹, Thomas Kampf¹, Walter H. Kullmann², Peter M. Jakob¹, Volker Christian Behr¹

¹Experimental Physics 5, University of Würzburg, Würzburg, Germany; ²Electrical Engineering, University of Applied Sciences Würzburg-Schweinfurt, Germany

Stem cell tracking is being performed in NMR as an indirect measurement of effects caused by iron nanoparticles which suffers from ambiguity and strong background dependency of the observed signal changes. Recently a method for direct imaging of magnetic particles has been introduced. Here a setup for spectroscopic detection of magnetic nanoparticles along with measurements to characterize those particles and to detect labeled stem cells is presented.

                  909.       Increased CNR in On-Resonance PARACEST Imaging

Craig K . Jones¹, Alex Li², Ravi S. Menon^1,2, Robert Bartha^1,2

¹CFMM, Robarts Research Institute, UWO, London, ON, Canada; ²Dept of Medical Biophysics, UWO, London, ON, Canada

On-resonance PARACEST contrast uses a short, low power 360º Waltz pulse to induce a signal intensity change in the measured water due to PARACEST compounds. In vivo this results in a significant decrease in the measured water signal due to the macromolecules. A post-saturation delay increases the contrast to noise ratio by a factor of 2 or more. The optimal delay depends on voxel T1 but a delay between 300 and 400 ms is sufficient for the Tm-DOTAM-glycine-lysine tested.

                  910.       Design of a Novel, MRI-Compatible Bioreactor for Longitudinal Monitoring of Mechanically Conditioned Engineered Cardiovascular Constructs

Sharan Ramaswamy¹, Steven Boronyak¹, Margot Goldberg¹, Paul Schornack¹, Michael Sacks¹

¹McGowen Institute for Regenerative Medicine, Pittsburgh, PA, USA

A novel MRI-compatible bioreactor is presented. This device permits noninvasive assessment of cell fate and evolving, in-situ tissue morphology. Between MR experiments, engineered tissue constructs can be mechanically conditioned via coupled or decoupled flow, stretch and flexure stress states. The effects of the different modes of mechanical stimuli on tissue formation and how thiseffects the distribution of the seeded cells can be studied using this device. This may ultimately be critical in optimizing currently used protocols in cardiovascular tissue engineering studies.

                  911.       Two-Compartment Pharmacokinetic Modeling of Targeted Molecular MRI Contrast Agents

Marlies Oostendorp^1,2, Kim Douma^1,2, Tilman M. Hackeng^1,2, Marc A.M.J. van Zandvoort^1,2, Mark J. Post^1,2, Walter H. Backes^1,2

¹Maastricht University Medical Centre, Maastricht, Netherlands; ²CARIM, Maastricht, Netherlands

The dynamic homing behavior and pharmacokinetics of targeted molecular MRI contrast agents are largely unknown. Moreover, it is unknown whether these typically large particles can penetrate the entire tissue or not. Here, a simple two-compartment model is presented that provides unique information on the pharmacokinetic behavior of cNGR-labeled paramagnetic quantum dots (cNGR-pQDs) targeted to the angiogenic tumor vasculature in mice. Compared with a non-targeted control particle, significant differences were found in both association and dissociation related parameters. In addition, significant differences were found throughout the tumor, indicating that the targeted contrast agent can indeed penetrate the entire tumor tissue.

                  912.       Laser Ablation ICP MS Imaging for the Detection of Contrast Agents in Tumour Tissue: Correlation to MR Images.

Tammy Kalber¹, John Pugh², Nazila Kamaly³, Jose Bunch², Jimmy Bell¹, Andrew Miller³, Cameron McLeod²

¹Metabolite and Molecular Imaging Group, ISD, MRC CSC, Hammersmith Hospital, Imperial College London, London, UK; ²Centre for Analytical Sciences, Department of Chemistry, University of Sheffield, Sheffield, UK; ³Imperial College Genetic Therapies Centre, Department of Chemistry, Imperial College London, London, UK

Laser ablation-inductively coupled plasma mass spectrometry (LA-ICP MS) was used to map the distribution of Gadolinium (Gd) in solid tumour tissues a various time points after inoculation of three different Gd containing contrast agents (targeted and non-targeted). The Gd maps were then compared to MR images of the same tumour at the same time point, and Gd maps correlated well with signal intensity changes in MR. However, LA-ICP MS was able to detect substantial amounts of Gd within tumour tissue although no signal change was apparent. It was also shown that specific targeting improves the correlation between both techniques.

                  913.       In Vivo Evaluation of the Specificity of Novel Drugs Targeting Dopamine D3 Receptors Using MRI: Role of Positive and Negative Hemodynamic Indices

Ji-Kyung Choi¹, Joseph B. Mandeville¹, Y. Iris Chen¹, Peter Grundt², Amy H. Newman³, Bruce G. Jenkins¹

¹Radiology, Athinoula Martinos Center for Biomedical Imaging, Charlestown, MA, USA; ²Medicinal Chemistry, NIDA, Baltimore, MD; ³Medicinal Chemistry, NIDA, Baltimore, MD, USA

Identifying the specificity of novel drugs targeting brain receptors is difficult and often requires synthesis of a radiolabel to determine in vivo specificity. We demonstrate the utility of pharmacologic MRI for identifying the specificity of dopamine D3 receptor drugs. D3 antagonists induce positive CBV and D3 agonists negative CBV changes in brain regions corresponding to the distribution of D3 receptors. Further, we show that these drugs induce positive CBV changes in cortical laminae with D1 receptors and negative CBV changes in cortical laminae with D3 recpetor innervation. MRI should prove to be a useful tool for characterization of novel drugs.

                  914.       Coupling ¹⁸F-Deoxyglucose PET Imaging and MRS at 14T of the in Vivo GLUT8 Knockout Mouse Brain

Carole Lynn Poitry-Yamate¹, Bernard Lanz¹, Hongxia Lei¹, Frederic Prietner², Stephane Germain¹, Bernard Thorens², Rolf Gruetter^1,3

¹IPMC, EPFL, Lausanne, Vaud, Switzerland; ²University of Lausanne, Lausanne, Vaud, Switzerland; ³Radiology, University of Lausanne and Geneva, Switzerland

We have undertaken the first combined study of ¹⁸FDG PET imaging and NMR spectroscopy of GLUT8 KO mice in vivo. Accumulated, intracellular ¹⁸FDG-6-phosphate was increased in functionally distinct brain regions of GLUT8 KO mice relative to WT mice, while regional brain glucose concentrations remained unchanged. Given that GLUT8 is localized to an intracellular storage site, these findings were unexpected. Possibilities to account for these observations are presented.

                  915.       Imaging of SPIO Labelled Endothelial Networks at 3, 7 and 11.7 Tesla

Clemens Diwoky¹, Andreas Reinisch², Dieter Gross³, Volker Lehmann³, Dirk Strunk², Rudolf Stollberger¹

¹Inst. of Medical Engineering, TU Graz, Graz, Austria; ²Stem Cell Research Unit, Dept. of Hematology, Univ. Clinic of Internal Medicine, Medical University of Graz, Graz, Austria; ³Dept. of Microimaging, Bruker BioSpin GmbH, Rheinstetten, Germany

Within this study we introduce an in-vitro model for the evaluation of cell detection strategies and SPIO cell load based on cell networks build by endothelial progenitor cells. This in-vitro correlate of the vasculogenesis process allows us to review MRI systems with different field strengths and gradient performances for their capabilities on single cell detection. High resolution (55µm) 3D GRE images at 3, 7 and 11.7 Tesla systems are investigated and the impact of different field strength and gradient performance on the image quality is examined.

                  916.       Complete Clearance of Iron Oxide from Intracerebrally Transplanted, Proliferating Neural Stem Cells

Piotr Walczak^1,2, Martijn L.L Chatrou³, Luc W.E Starmans³, Assaf A. Gilad^1,2, Klaas Nicolay³, Jeff W.M Bulte^1,2

¹Radiology, Johns Hopkins University, Baltimore, MD, USA; ²Institute for Cell Engineering, Johns Hopkins University, Baltimore, MD, USA; ³Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands

Cell-based therapy of neurodegenerative disorders has shown considerable potential for clinical translation. The implementation of new non-invasive imaging techniques is needed to expedite further progress in this field. MR imaging of magnetically labeled cells is currently considered the method of choice for cellular imaging; however, proliferation and death of labeled cells with transfer of contrast to surrounding phagocytes are elements that may confound interpretation of the results. We show that intracellular Feridex is completely cleared by 95 days after cell transplantation regardless of potential host transfer to tissue macrophages.

                  917.       19F MRI and C-Arm CT Guiding of Reporter Probe Injection to Microencapsulated Mesenchymal Stem Cells for in Vivo Cell Viability Assessment with Bioluminescence Imaging°° >

Dorota A. Kedziorek¹, Piotr Walczak¹, Yingli Fu¹, Tina Ehtiati², Alexander B. Brost³, Nicole Azene¹, Gary Huang¹, Jeff W.M. Bulte¹, Steven M. Shea², Robert Krieg⁴, Ronald Ouwerkerk¹, Frank K. Wacker¹, Dara L. Kraitchman¹

¹Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA; ²Imaging and Visualization, Siemens Corporate Research Inc., Baltimore, MD, USA; ³Department of Computer Science, University of Erlangen-Nuremberg , Erlangen, Germany; ⁴Siemens AG Healthcare Sector, Erlangen, Germany

The major problems with stem cell therapies are the poor cell survival and engraftment; both could be optimized with the use of non invasive imaging. In the present study, mesenchymal stem cells were engineered to express firefly luciferase (bioluminescence (BL) reporter gene) to monitor their survival and microencapsulated in perfluorooctylbromide (PFOB) alginate capsules. Bioluminescent, microencapsulated MSCs were transplanted into a rabbit model of peripheral arterial disease. C-arm CT was used to localize the radiopaque PFOB microcapsules for accurate injections of the BL probe directly into the injection sites. 19F MRI was used to demonstrate the PFOB capsules locations.

                  918.       In Vivo Monitoring of Transplanted Human Embryonic Stem Cell-Derived Oligodendroglial Progenitors in a Mouse Model of Multiple Sclerosis

Heechul Kim^1,2, Candace Kerr^3,4, Naser Muja^1,2, Piotr Walczak^1,2, Jeff W.M. Bulte^1,2

¹Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; ²Cellular Imaging Section, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; ³Dept. of Gynecology and Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; ⁴Stem Cell Biology Program, , Institute for Cell Engineering , The Johns Hopkins University School of Medicine, Baltimore, MD, USA

Feridex-labeled hESC-derived oligodendroglial progenitors were transplanted and tracked in a mouse model of multiple sclerosis. Feridex-labeling did not impair the therapeutic benefit induced by transplanted cells. At day 1 post-tx, hypointense MRI signals were detected mainly in the ventricle and subventricular zones. These signals persisted on days 5, 15, and 30 post-tx.The hypointense areas within the ventricle were significantly decreased at day 30 post-tx as compared to days 1, 5, and 15. Based on the above results, we postulate that cell migration mainly occurs through the ventricular system to the parenchyma during days 15-30 post-tx.

                  919.       Microfabrication of Multifunctional Alginate Capsule-In-Capsule (CIC) for Immunoprotected Cell Transplantation with MR, CT, and US Visibility

Jaeyun Kim^1,2, Dian R. Arifin¹, Naser Muja¹, Assaf A. Gilad¹, Taeho Kim^1,2, Aravind Arepally¹, Taeghwan Hyeon², Jeff WM Bulte¹

¹Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; ²Chemical and Biological Engineering, Seoul National University, Seoul, Korea

A novel alginate capsule-in-capsule (CIC) preparation was designed and microfabricated for immunoprotected cell transplantation with multimodal tracking capability including MRI, micro-CT, and ultrasound imaging. Using the dual capsule (CIC) approach for physical separation of human islets from the NPs, a better viability and cell function including glucose responsiveness and insulin secretion can be retained as compared to single Feridex/Au NP capsules. The CICs injected in peritoneal cavity in live mice were easily visualized on MRI, CT, and ultrasound.

                  920.       Evaluation of Nanoparticle Contrast Agent Uptake in Murine Microglia (Bv-2) and Human Teracarcinoma (NT2) for Cell Tracking in Neurodegenerative Disease at 21.1 T

Jens Thorvald Rosenberg^1,2, Joshua M. Kogot³, Chris Ridel³, Geoffery F. Strouse³, Samuel C. Grant^1,2

¹The National High Magnetic Field Laboratory, Tallahassee, FL, USA; ²Chemical and Biomedical Engineering, Florida State University, Tallahassee, FL, USA; ³Chemistry and Biochemistry, Florida State University, Tallahassee, FL, USA

We have assessed murine microglia cells (Bv-2) and human teratocarcinoma cells (NT2) for future use with a novel bimodal MR contrast agent. These cells can be used to identify regions of neurodegeneration. To evaluate contrast enhancement, we have compared the performance of our bimodal agents consisting of Dy-label quantum dots to SPIOs and Dy chelates (DOTA and DTPA).

                  921.       Iron Oxide Labeling of Mesenchymal Stem Cells with Micrometer-Sized Particles: Applications to Cartilage Tissue Engineering

Karl Saldanha¹, Ryan Doan^1,2, Sharmila Majumdar¹

¹Department of Radiology, UCSF, San Francisco, CA, USA; ²Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA

Mesenchymal stem cells (MSCs), have demonstrated differentiation into chondrocytes, with applications to treating cartilage defects or osteoarthritis. Iron oxide labeling of MSCs before implantation may enable longitudinal non-invasive in vivo assessment of cells via magnetic resonance imaging (MRI). This study examined MSC labeling with micrometer-sized iron oxides (MPIOs) and the effect of labeling on chondrogenesis. Results indicate cellular uptake of MPIOs, with associated signal loss on MR images at clinically relevant field strengths. While labeling does not inhibit chondrogenesis, the presence of extracellular iron may have implications for the effectiveness of using MRI to monitor stem cell-based cartilage regeneration.

                  922.       Efficient Labeling of Dendritic Cells with a Clinical Applicable Perfluorpolyether Compound for Quantitative 19F MRI Tracking in Cancer Patients

Fernando José Bonetto¹, Mangala Srinivas¹, Arend Heerschap², Robbie Mailliard³, Eric T. Ahrens⁴, Carl Figdor⁵, Jolanda de Vries⁶

¹Tumor Immunology, Nijmegen Centre for Molecular Life Science, Radboud University Nijmegen medical Centre, Nijmegen, Gelderland, Netherlands; ²Radiology, Radboud University Nijmegen Medical Center, Nijmegen, Gelderland, Netherlands; ³Celsense Inc., Pittsburgh, USA; ⁴Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA; ⁵Nijmegen Centre for Molecular Life Science, Radboud University Nijmegen Medical Center, Nijmegen, Gelderland, Netherlands; ⁶Tumor Immunology, Nijmegen Centre for Molecular Life Science, Radboud University Nijmegen Medicla Centre, Nijmegen, Gelderland, Netherlands

Tracking of cells using contrast agents with magnetic resonance imaging provides detailed anatomical information but it lacks quantitative information. A new perfluoropolyether nanoemulsion was studied for labeling of dendritic cells for 19F MRI. Our results demonstrate that the compound is taken up by the cells and does not hamper cell function ( viability, maturation and mRNA uptake).

                  923.       In Vivo MR Imaging of the Recruitment of Iron Oxide–labeled Macrophages in Renal Ischemic-Reperfusion Model in Mice

Quan-Yu Cai¹, Hyo-Eun Park¹, Hyeyoung Moon¹, Kwan Soo Hong¹

¹Magnetic resonance imaging team, Korean basic science institute, Ochang, Cheongwon-Gun, Chungcheongbuk-Do, Korea

Clinical Acute Renal Failure is a common renal disease, still associated with high morbidity and mortality. Visualization of macrophage homing is important to assess the dynamic evaluation of the recruitment of immune cells. Our study demonstrated that intravenously administered iron oxide–labeled macrophage homing to injured kidney can be monitored with 4.7-T MR imaging. Contrast enhancement 24 hours after administration of iron oxide–labeled macrophages is sharply defined. MR imaging for macrophage homing may provide a tool to early detection and investigate pathogenesis of acute renal failure and a guide for immunotherapy.

                  924.       Migration Dynamics of Neural Progenitor Cells Revealed by MRI

Brian John Nieman^1,2, Jeffrey Y. Shyu¹, Joe J. Rodriguez¹, Daniel H. Turnbull^1,2

¹Skirball Institute, New York University School of Medicine, New York, NY, USA; ²Department of Radiology, New York University School of Medicine, New York, NY, USA

Neural progenitor cells from the subventricular zone are of particular importance for replacing interneurons in the olfactory bulb throughout life and may hold therapeutic potential following brain injury. We investigated the migratory capacity of these cells by longitudinal MRI after endogenous labeling with micron-sized particles of iron-oxide. Cells were observed to move as fast 109 μm/hr in the rostral migratory stream, but more slowly as they distribute through the bulb over the course of three weeks. In the bulb, we observed that most labeled cells were neuronal.

                  925.       Single Cell Tracking of Neural Progenitors Labeled in Vivo with Micron Sized Particles of Iron Oxide (MPIO) Into Specific Layers of the Olfactory Bulb

James P. Sumner¹, Stephen Dodd¹, Elizabeth Wayne^1,2, Der-Yow Chen¹, Yun Chen^1,3, Dragan Maric^1,4, Alan P. Koretsky¹

¹National Institutes of Health, Bethesda, MD, USA; ²University of Pennsylvania, Philadelphia, PA, USA; ³National Institute of Standards and Technology; ⁴NINDS FACS Facility, Bethesda, MD, USA

In this work, MRI was used to track neural progenitors (NPCs) into the olfactory bulb with 50 μm isotropic resolution. At this resolution and with the aid of manganese, NPCs were identified and quantified in each layer of the bulb. Olfactory bulbs from naive and animals exposed to amyl acetate were compared.

                  926.       Inflammation Imaging of Atherosclerosis: MRI of Iron Oxide-Labelled Macrophages Trafficking in ApoE2 (KI) Mice Lesions

Amine Bessaad¹, Monica Sigovan¹, Hasan Alsaid¹, Genviève De Souza1¹, Nicolas Provost², Zoher Majd², Christine Menager³, Norbert Nighoghossian1¹, Serge Nataf⁴, Emmanuelle Canet-Soulas1¹

¹Université Lyon 1  CREATIS - LRMN, UMR CNRS 5220, U630 INSERM, Villeurbanne, Rhône, France; ²GenFit, Lille, France; ³UPMC, Paris, France; ⁴inserm U842, Lyon, Rhône, France

MRI caracterisation of atheroma plaque in aortic arch of mice ApoE2 (K.I) by using Anionic Magnetic Nano Particules of iron oxide labelled macrophages and assessment of inflammatory status of atheroma plaques by follow up during 3 days post-contrast, allows us to detect the macrophages after migration distributed in intimal and/or adventitial localization. this is promising for vectorization and assessement of traitement accuracy

                  927.       Cellular MR Imaging of Immune Cells Infiltration as a Marker for Assessment Allograft Outcome in a Chronic Cardiac Allograft Rejection Rat Model

QING YE¹, Yijen Lin Wu¹, Lesley M. Foley¹, T K. Hitchens¹, Hao Sen Zhang¹, Danielle Eytan¹, Chih Lung Chen², Chien Ho¹

¹NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, PA, USA; ²Industrial technology research institute, Taiwan

Chronic cardiac allograft rejection (CCAR) remains a major obstacle for long-term survival after heart transplantation. Non-invasive assessment of cardiac allograft status is highly desirable. We are developing non-invasive means for detecting allograft rejection by using MRI techniques. Because immune cells are involved in the development of CCAR, in this study, we used a chronic rejection working heart rat model and labeled immune cells in situ with micrometer-sized paramagnetic iron oxide particles. The accumulation of labeled cells in rejecting allograft was monitored with cellular MRI. Our data shows that MRI detection of rejection is well correlated with the pathology changes.

                  928.       In Vivo Differentiation of Magnetically Labeled Mesenchymal Stem Cells Into Hepatocytes for Cell Therapy to Repair Damaged Liver

Shenghong Ju¹, Gao-jun Teng¹, Haihua Lu¹

¹Department of Radiology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China

The aims of this study are to build a new in vivo model named as “Iron-GFP/CCl4 model” for monitoring the transdifferentiation of magnetically labeled GFP-positive MSCs into albumin-positive hepatocytes under the specific “niche” made by CCl4 induced persistent liver damage, and to track labeled MSCs by MR imaging in vivo in mice.

                  929.       Serial Monitoring and Quantification of Endogenous Neuroblast Migration Rates by Cellular MRI

Dorit Granot¹, Dustin Scheinost¹, Xenophon Papademetris^1,2, Erik M. Shapiro^1,2

¹Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA; ²Department of Biomedical Engineering, Yale University, New Haven, CT, USA

Here we quantified the rate of migration of native neuroblasts into the olfactory bulb by MRI. Neuroblasts were labeled in-vivo by direct injection of MPIOs into the ventricle. Following labeling, we measured a linear accumulation of newly arriving cells in the OB. At day 1, cells were not found in the OB. By day 3, cells were observed entering the central portion of the OB. At day 8, many cells were detected in the central portion of the OB and in the outer edges. MRI detection of migration plateaued at week 1, indicating that the MPIO injection was a bolus.

                  930.       Intravenous Injection of Fluorescent Iron-Oxide Nanoparticles for in Vivo Loading and Tracking of Monocytes to Myocardial Infarction by MRI and Optical Imaging

Karin Montet-Abou¹, Jean-Luc Daire¹, Jean-Noel Hyacinthe¹, Francois Mach², Alke Petri-Fink³, Heinrich Hofmann³, Denis R. Morel⁴, Jean-Paul Vallee¹, Xavier Montet¹

¹Radiology, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland; ²Cardiology, Geneva University Hospital, Geneva, Switzerland; ³Laboratory of Powder Technology, EPFL, Lausanne, Vaud, Switzerland; ⁴Anesthesiological Investigation Unit, Geneva University Hospital, Geneva, Switzerland

Inflammatory cells are involved in numerous pathologies, including myocardial infarction. In the case of myocardial infarction the majority of the infiltrating cells are monocytes/macrophages. This study demonstrates that monocytes/macrophages can be loaded in vivo by a simple intravenous injection of fluorescent superparamagnetic iron oxide and then tracked, in the same animal, in a model of ischemia-reperfusion leading to myocardial infarct.

                  931.       Comparison of Iron-Oxide- And Perfluorocarbon-Based Cellular Contrast Agents for Detecting Immune Cell Infiltration in Models of Organ Transplant Rejection

T. Kevin Hitchens^1,2, Qing Ye¹, Danielle F. Eytan^1,2, Yijen L. Wu¹, Jelena M. Janjic^1,2, Eric T. Ahrens^1,2, Chien Ho^1,2

¹Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, PA, USA; ²Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA

Cellular imaging is an emerging and important field in magnetic resonance. We are developing cellular MRI techniques for detecting rejection following organ transplantation and the selection of the appropriate contrast agent is necessary to achieve our goals. Several types of agents exist that provide fundamentally different image contrast. Our rat models of kidney and heart transplantation provide good systems to evaluate the advantages and disadvantages of iron-oxide-based and 19F-based agents for detecting immune cells in vivo by MRI. Because each type of agent has different imaging properties, in many cases, iron-oxide- and 19F-based agents can provide complementary information.

                  932.       Using Ferritin as a Transgenic MRI Reporter for Monitoring of Embryonic Stem Cell Graft in Vivo

Hui Mao^1,2, Jun Liu^2,3, Eric C. Cheng², Rober C. Long⁴, Shang Hsun Yang², Liya Wang⁴, Pei Hsun Cheng², Jin jing Yang², Anthony W.S. Chan²

¹Department of Radiology, Emory Unversity School of Medicine, Atlanta, GA, USA; ²Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, GA, USA; ³Neuroscience program, Emory University School of Medicine, Atlanta, GA, USA; ⁴Department of Radiology, Emory University School of Medicine, Atlanta, GA, USA

MRI reporters based on endogenous gene expression for MRI contrast offers advantages in longitudinal cell monitoring. Engineering stem cells with an MRI reporter may enable long term in vivo tracking implanted cells with MRI. We report a study on introducing a MRI reporter gene (ferrotin) into mouse ES (mES) cells and successful monitoring of transgenic mES cell grafts in mice. Transgenic mES cell lines carrying human ferritin heavy chain were established and T2 weighted MRI and multiple-TE T2 relaxometry of mice carrying mES cell grafts showed T2 contrast and significantly decreased T2 relaxation time in transgenic mES graft overexpressing ferritin.

                  933.       Evaluation of LV and AAV Vector Systems for Stable Delivery of MRI Reporter Genes to the Rodent Brain

Greetje Vande Velde¹, Janaki Raman Rangarajan², Tom Dresselaers³, Olga Krylyshkina¹, Abdelilah Ibrahimi¹, Zeger Debyser¹, Veerle Baekelandt¹, Uwe Himmelreich³

¹Molecular Medicine, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium; ²Medical Imaging Center, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium; ³Biomedical Nuclear NMR unit, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium

Utilizing lentiviral (LV) and adeno-associated (AAV) viral vector systems for delivering MRI reporter genes (e.g. ferritin) will allow stable labeling and in vivo visualization of marked cells, but their potential limitations for MRI are often insufficiently addressed. Injection in rodent brain of LV/AAV without MRI reporter genes results in hypointense contrast at the injection site on T2*-weighted MRI that correlates with the presence of Fe3+ and microglia. This challenges the signal-to-noise properties of putative MRI reporter genes.

                  934.       MRI Reporter Gels to Detect Enzymes and Cells in Vivo

Jason Colomb¹, Ameya Jategaonkar¹, Kevin M. Bennett¹

¹Harrington Department of Bioengineering, Arizona State University, Tempe, Az, USA

                  937.       Susceptibility Weighted Imaging Complements Diffusion Tensor Imaging in Traumatic Brain Injury

Zhifeng Kou¹, Randall R. Benson², Ramtilak Gattu¹, E Mark Haacke¹

¹Radiology, Wayne State University, Detroit, MI, USA; ²Neurology, Wayne State University, Detroit, MI, USA

Diffusion tensor imaging (DTI) and susceptibility weighted imaging (SWI) have been reported to be sensitive to white matter injury and microhemorrhages, respectively, in traumatic brain injury (TBI). We developed an approach to complementary using both SWI and DTI to improve the detection of TBI. Our data showed that DTI is sensitive to white matter injury that looks normal in structural imaging, including SWI; and SWI is sensitive to microhemorrhages at gray matter and gray/white matter junctions that DTI and conventional MRI fail to detect. A complementary use of both DTI and SWI could improve the detection of traumatic brain injury.

                  938.       Comparison of MR Imaging Methods for Pre-Surgical Localisation of the Subthalamic Nucleus and Globus Pallidus

Ruth L. O'Gorman¹, Stephen J. Wastling², Michelle Footman², David J. Lythgoe³, Michael Samuel⁴, Richard Selway⁵, Keyoumars Ashkan⁵, Jozef Jarosz¹

¹Neuroradiology, King's College Hospital, London, UK; ²Medical Engineering and Physics, King's College Hospital, London, UK; ³Centre for Neuroimaging Sciences, Institute of Psychiatry, London, UK; ⁴Neurology, King's College Hospital, London, UK; ⁵Neurosurgery, King's College Hospital, London, UK

The subthalamic nucleus (STN) and globus pallidus (GPi) are two common target structures used for deep brain stimulation. These structures are typically localised from T2 or PD FSE images, but their visibility may be improved with alternative MRI methods. This study quantitatively compared the contrast to noise ratio of the STN and GPi with a range of MRI sequences including susceptibility weighting (SWI) and T2* mapping. For the STN, the SWI, T2*, and late echo gradient echo images demonstrate comparable or better contrast relative to the standard T2 FSE. For the GPi, the standard PD FSE demonstrates the highest contrast.

                  939.       Optimal Parameters of Suppor Vector Machine for Classification of Multispectral Brain MRI

Hsian-Min Chen¹, Jyh-Wen Chai², San-Kan Lee², Clayton Chi-Chang Chen², Ying-Cheng Lin³, Yen-Chieh Ouyang³, Chein-I Chang⁴, Wu-Chung Shen¹

¹Department of Radiology, China Medical University Hospital, Taichung, Taiwan; ²Department of Radiology, Taichung Veterans General Hospital, Taichung, Taiwan; ³Department of Electrical Engineering, National Chung Hsing University, Taichung, Taiwan; ⁴Remote Sensing Signal and Image Processing Laboratory, Department of Computer Science and E.E., University of Maryland, Baltimore County, USA

Support vector machine (SVM) has been widely used as a powerful tool for classification problem arising from various fields and shown that the parameters are critical in the performance of SVM [1]. However, the same parameters are not suitable for all classification problems. In this paper, numerical results show that the performance of SVM with optimal parameters is significant difference to empirical parameters. In addition, we recommend independent component analysis (ICA) method as the pre-processing step to get the robust performance of SVM classification problems in brain MRI.

                  940.       First Upright Study of CSF Flow in Chiari I Malformation with Cine Phase-Contrast MRI

David Chu¹, Michael Boitano, Dan Culver, Raymond Damadian, Mary Gianni, Rob Viel, Jan Votruba, Robert Wolf

¹Fonar Corporation, Melville, NY, USA

Cerebrospinal fluid (CSF) flow abnormalities are generally known to correlate better with symptomatology than the degree of tonsillar herniation in Chiari I malformation (CMI) patients. However, all MRI studies of CSF flow in CMI patients have been restricted to the recumbent position. We present the first study of CSF flow and spinal cord pulsation in the upright posture in a CMI patient. Upright imaging revealed major CSF flow abnormalities that were absent in the supine posture.

                  941.       Identification of Traumatic Subarachnoid Hemorrhage Using Susceptibility Weighted Imaging

Jing Lei¹, Zhen Wu², Meili Liu¹, Tong Han¹, Ewart Mark Haacke^2,3

¹Radiology, Tianjin Huanhu Hospital, Tianjin, China; ²Biomedical Engineering, McMaster University, Hamilton, On, Canada; ³Radiology, Wayne State University, Detroit, MI, USA

Subarachnoid hemorrhage (SAH) is related to poor outcome in traumatic brain injury (TBI). Susceptibility weighted imaging (SWI) has been successfully applied in TBI and proved to be very sensitive to hemorrhage. This study compared CT, FLAIR and SWI in 20 TBI patients with SAH. The results showed SWI is sensitive to small amount of SAH located within the sulci and better than CT in detecting intra-ventricle hemorrhage. The aliasing effect on phase images helps to differentiate SAH from veins. But SWI is not as good as CT in detecting basilar cistern SAH.

                  942.       Quantitative Susceptibility Imaging with Homotopic L0 Minimization Programming: Preliminary Study of Brain

Jing Liu¹, Tian Liu¹, Ludovic de Rochefort¹, Martin R. Prince¹, Yi R. Wang¹

¹Radiology, Weill Cornell Medical College, New York, NY, USA

Quantitative susceptibility imaging improves upon susceptibility weighted imaging by measuring iron in brain tissues, which can be used to analyze brain function and identify neurological diseases. We proposed an efficient approach based on homotopic L0 norm minimization programming to solve the inverse problem from magnetic field measurement to susceptibility map. Results of brain exams have demonstrated the quantitative visibility of hemorrhage, veins and gray matter.

                  943.       MRI Estimation of Global Brain Oxygen Consumption Rate

Varsha Jain¹, Michael Langham², Jeremy Magland², Felix Wehrli²

¹Department of Bionegineering, University of Pennsylvania, Philadlephia, PA, USA; ²Department of Radiology, University of Pennsylvania, Philadlephia, PA, USA

Measuring the cerebral metabolic rate of oxygen (CMRO2) can serve as a valuable tool for monitoring severely brain injured patients. We demonstrate MRI-based CMRO2 quantification by measuring blood oxygenation difference between major inflow and outflow vessels with MR susceptometry-based oximetry and average blood inflow rate with gated phase-contrast MRI. MR susceptometry-based oximetry relies on the magnetic susceptibility of the intravascular blood and the surrounding tissue, the latter serving as a calibration free reference. Preliminary results obtained in two healthy human subjects, a 36 year old male and a 23 old female, CMRO2 values of 3.9 and 2.4 mL/100g/min, respectively are consistent with literature.

                  944.       MRI Derived Intracranial Compliance in Patients with Idiopathic Intracranial Hypertension

Luca Nocetti¹, Alessandra Mantovani², Federica Tavani³, Milena Cobelli³, Stefano Vallone³, Claudio Danielli¹, GianPietro Pinna⁴

¹Health Physics, University Hospital "Policlinico", Modena, Italy; ²Neurosurgery, University of Modena, Modena, Italy; ³Neuroradiology, Hospital "NOCSE", Modena, Italy; ⁴Neurosurgery, Hospital "NOCSE", Modena, Italy

Idiopathic intracranial hypertension (IIH) is a neurological disorder that is characterized by increased intracranial pressure (ICP) in the absence of a tumor or other diseases. Intracranial compliance (ICC), the variation of the Intracranial Volume (ICVC) and local craniocervical hydrodynamic parameters derived using magnetic resonance (MR) imaging flow measurements were assessed in patients and control volunteers to evaluate the role of these factors in the associated pathophysiology.Seventeen patients with IIH diagnosis and a mean age 39±10 years and fourteen healthy volunteers that report no history of neurological disorders and a mean age 27±3 years were studied using a 3-tesla MR imager; both patients and volunteers were all females. Differences in the systolic cervical CSF velocity and flow and the mean volume between the systolic and the diastolic phase, comparing healthy volunteers and patients with IIH, were not statistically significant. Were instead observed in patients compared with controls a statistically significant lower ICVC (p<0.036) and ICC (p<0.015). Analysis of results have indicated that ICC and ICVC are more sensitive than local hydrodynamic parameters to changes in the craniospinal biomechanical properties in IIH patients.

                  945.       Compensating for Field Strength with Coils; Comparison of SNR at 1.5T, 3T and 7T with 12 and 32 Channel Arrays

Mattijs Elschot^1,2, Lawrence L. Wald^1,3, Stephan Biber⁴, Michael Hamm⁵, Christina Triantafyllou^1,6

¹A.A. Martinos Center for Biomedical Imaging, Department of Radiology, MGH, Charlestown, MA, USA; ²Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands; ³Harvard-MIT Division of Health Science and Technology, Cambridge, MA, USA; ⁴Siemens HealthCare, Erlangen, Germany; ⁵Siemens Medical Solutions USA Inc., Charlestown, MA, USA; ⁶A.A. Martinos Imaging Center, McGovern Institute for Brain  Research, MIT, Cambridge, MA, USA

Sensitivity in MR detection generally comes at considerable expense. Presumably, acquiring images with the most sophisticated close-fitting coil at the highest field strength is always the most sensitive approach to MR detection.

                  946.       Histological Validation of Hemorrhage and Temporal Blood Transformation Detected by Susceptibility Weighted Imaging in Traumatic Brain Injury

Zhifeng Kou¹, Yimin Shen¹, Nirsine Zakaria², Srini Kallak³, John Cavanaugh³, E Mark Haacke¹

¹Radiology, Wayne State University, Detroit, MI, USA; ²Biomedical Engineering, Wayne State University, Detroit, USA; ³Biomedical Engineering, Wayne State University, Detroit, MI, USA

Susceptibility weighted imaging (SWI) has demonstrated to be extremely sensitive to microhemorrhages after trauma. However, no data has been reported to validate SWI findings as blood products. In this study, histological validation (Prussian Blue staining) in a brain injury animal model was performed to prove that microhemorrhages detected by SWI in traumatic brain injury do represent blood products. SWI also demonstrated a temporal pattern of hemorrhagic blood transformation in brain trauma. Our data suggested that an appropriate timing point is critical to acutely detect blood product after trauma.

                  947.       Cross-Sectional Automatic Measurement of Brain Volume on MRI: Reproducibility of KNN-Based Probabilistic Segmentation

Jeroen de Bresser^1,2, Cynthia Jongen^1,3, Petronella Anbeek¹, Max A. Viergever¹, L. J. Kappelle², G. J. Biessels²

¹Image Sciences Institute, University Medical Center, Utrecht, Netherlands; ²Department of Neurology, University Medical Center, Utrecht, Netherlands; ³Department of Neurology, University Medical Center , Utrecht, Netherlands

The reproducibility of volumetric measurements of different brain structures (sub-cortical structures (SCS), cortical gray-matter (CGM), cerebro-spinal fluid, lateral ventricles, white-matter lesions and total brain (SCS+CGM)) by kNN-based probabilistic segmentation (kNN) was assessed.

                  948.       Magnetic Field Distortion Caused by Intracapillary Red Blood Cells

Toru Yamamoto¹, Osamu Tsuchida², T. Omatsu³

¹Graduate School of Health Sciences, Hokkaido University, Sapporo, Hokkaido, Japan; ²Teishinkai Hospital, Japan; ³Hokkaido Univeisity Hospital, Japan

Each red blood cell (RBC) that discretely flows through a capillary distorts the magnetic field of magnetic resonance imaging. This distortion spreads over a micrometer range around the RBC and moves along the capillary, causing fast transverse relaxation. To investigate the changes in this fast transverse relaxation that occur due to blood oxygenation changes, we performed consecutive spin-echo imaging of human brain for 50 minutes with short (5.5 ms) and long (88 ms) echo times. The signal in the sagittal sinus showed a gradual decrease in blood oxygenation. Changes in the transverse relaxation rate in brain parenchyma observed in images with short echo time were more than ten times of those with long echo time.

                  949.       The Allen Institute Mouse Brain Gene Expression Data Co-Aligned with a Mouse MRI Atlas

Jason Philipp Lerch¹, Chris Lau², Lydia Ng², Michael Hawrylycz², R. Mark Henkelman¹

¹Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada; ²Allen Institute for Brain Science, Seattle, WA, USA

The Allen Institute for Brain Science recently created a digital atlas of gene expression patterns in the adult mouse. Here we align these gene maps towards an MRI atlas and therefore provide the MR community with the ability to align gene expression maps with their mouse MRI results.

                  950.       Anatomical Phenotyping of the Knockout Mouse Model of Fragile X Syndrome

Jacob Ellegood¹, Laura K. Pacey², David R. Hampson³, Jason P. Lerch¹, R Mark Henkelman¹

¹Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada; ²Department of Pharmacy, University of Toronto, Toronto , Ontario, Canada; ³Department of Pharmacy, University of Toronto, Toronto, Ontario, Canada

Mutations of the FMR-1 (Fragile X Mental Retardation 1) gene cause a genetic condition know as Fragile X Syndrome (FXS). The Fragile X knockout mouse is the most widely used animal model of FXS. The purpose of this study was to assess anatomical changes between Fragile X knockout and wild type mice.

                  951.       High Resolution MRI of Enriched Environment Induced Structural Brain Changes

Ory Levy¹, Daniel M. Michaelson¹, Yaniv Assaf¹

¹Neurobiology, Tel Aviv University, Life sciences Faculty, Tel Aviv, Israel

One suggested preventive approach to white matter loss especially in Alzheimer's disease is neurogenesis. We examined the paradigm of neurogenesis induction by environmental enrichment (EN). Twelve C57BL/6J mice at the age of weaning were divided into two groups (control and enrichment). The enriched mice were kept 4 months in enrichment cages. All mice were scanned in a 7T magnet using DTI protocol. Our results showed that DTI revealed differences in known areas (the hippocampus) and added insight by pointing out more areas: the corpus callosum and the thalamus in which significant differences were found to exist after EN.

                  952.       MRI and 3D Visualization of Neurovascular Casts

Jeff F. Dunn^1,2, Cheryl R. McCreary, Andre Obenaus³, J Ross Mitchell⁴

¹Department of Radiology, University of Calgary, Calgary, Alberta, Canada; ²Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; ³Radiation Medicine and Radiology, Loma Linda University, USA; ⁴Department of Radiology, University of Calgary, Canada

Corrosion casts are a useful tool for studying the vasculature of normal, genetically altered, or diseased brain. Such casts are difficult to examine given that visual examination involves destroying the tissue surround the cast. Synchrotron-CT (X-CT) has been used for high resolution examination of the vasculature. Here we show that MRI microscopy can examine the cast structure in 3D and, combined with state of the art post-processing and visualization methods allows examination of vessels through multiple branch points to sizes of less than 60um in diameter.

                  953.       The Relationship Between Susceptibility Weighted Phase and White Matter Fiber Orientation.

Enedino Hernández¹, Alex MacKay², Alexander Rauscher³

¹Instituto de Física, Universidad de Guanajuato, León, Guanajuato, Mexico; ²Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, Canada; ³UBC MRI Research Centre, University of British Columbia, Vancouver, British Columbia, Canada

The origin of contrast in susceptibility weighted phase imaging (SWI) is not yet fully understood. Both grey and white matter show considerable heterogeneity on phase images. We investigated the relationship between white matter fiber orientation with respect to Bo (obtained from DTI data) and phase (obtained from SWI data). Phase was negative for fibers parallel and perpendicular to Bo and positive for intermediate orientations

                  954.       Ultra High Resolution Venography Using T2* Weighted Imaging at 7T MRI

Seo-Hyun Lee¹, Chang-Ki Kang¹, Chan-A Park¹, Seung-Taek Oh¹, Young-Bo Kim¹, Zang-Hee Cho¹

¹Neuroscience Research Institute, Gachon University of Medicine and Science, Incheon, Korea

High magnetic field strength potentially allows for an increase in resolution and image contrast, especially for imaging of the cerebral veins. The gains are particularly dramatic for T2*-weighted imaging, which is sensitive to susceptibility effects caused by a variety of sources, including deoxyhemoglobin, iron concentration, and tissue microstructure. The image quality and diagnostic value of MRI of venography were improved as field strength was increased. However, proper imaging resolution was not well evaluated. In this study, we will provide the ultra high resolution venography for imaging the micro-veins using T2*-weighted imaging at 7T MRI.

                  955.       Understanding the Orientation Dependent T2* Contrast of the Cingulum in Ultra High Fields

Andreas Schäfer¹, Christopher J. Wiggins^2,3, Robert Turner¹

¹Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; ²CEA NeuroSpin, Gif-sur-Yvette, France; ³IFR 49, Gif-sur-Yvette, France

It was shown recently that high resolution T2*-weighted images display T2* heterogeneity in white matter and an unexpected signal dependence in the cingulum bundles on head orientation to the main magnetic field. The signal change with orientation is still poorly explained. Here we used, in addition, phase images arising from high resolution spoiled gradient echo sequences, because such images are more sensitive to susceptibility effects. We also obtained TSE images to determine whether the orientation dependence of the signal appears in that sequence as well. Furthermore we compared the measurements with simulations using the forward field calculation.

                  956.       Grey/white Matter Contrast in Phase Images: Is It Susceptibility or Is It Not?

José Pedro Marques¹, Rolf Gruetter¹

¹Centre d'Imagerie BioMédicale, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Vaud, Switzerland

The tissue phase variations between grey and white matter are thought to originate from either tissue susceptibility variations or variations of macromolecule content affecting the water chemical shift. In this abstract we test these two hypotheses by trying to fit a high resolution fieldmap with the expected spatial distribution calculated after segmentation of a high resolution T1 weighted image. Results tentatively suggest the dominance of a non-susceptibility origin.

                  957.       Is R2* in Human Brain White Matter Dependent on B0 Orientation?

Tie-Qiang Li¹, Fukunaga Masaki², Stephen Dodd², Peter van Gelderen², Merkle Hellmut², Jeff H. Duyn²

¹Medical Physics, Karolinska Huddinge, Stockholm, Sweden; ²NINDS, NIH, Bethesda, MD, USA

The observation of T2* heterogeneity in white matter at high magnetic field strength [1] has invited speculation that white matter fiber orientation with respect to the main magnetic field (B0) might contribute to this contrast. To investigate this, we performed quantitative R2* measurements at different orientations in vivo and in fixed brain tissue samples.

                  958.       T₁-Weighted MRI Visualizes Functional Anatomy in the Marmoset Cortex

Nicholas A. Bock¹, Junjie Liu¹, Ara Kocharyan¹, Afonso C. Silva¹

¹CMU, LFMI, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesa, MD, USA

We hypothesize that differences in the amount of myelin present in functionally distinct regions of the cortex lead to T₁ differences that can be used to delineate these regions on MRI. To test this, we measured T₁s in cortical regions with high and low myelin contents of an anaesthetized non-human primate (the common marmoset) at 7 Tesla. We then used these values to optimize a high resolution, 3D, T1-weighted pulse sequence to visualize the pattern of myelination across the marmoset cortex and showed that we could identify major cortical regions.

                  959.       Stochastic Analysis of Transverse Relaxation Caused by Local Field Inhomogeneities in Iron-Rich Brain Tissue

John Frederic  Schenck¹

¹MRI Laboratory, General Electric Global Research, Schenectady, NY, USA

A modification of a classical stochastic solution to the problem of an ensemble of harmonic oscillators subjected to random frequency perturbations is modified to provide a simple formula capable of describing the details of transverse relaxation in the presence of iron deposits. This formula is widely applicable and extremely easy to use. It provides new insights into this important process and suggests new approaches to the imaging and analysis of brain iron deposits.

                  960.       Magnetic Resonance Imaging of Deep Brain Nuclei at 7 Tesla

Adrienne Nicole Dula^1,2, E B. Welch^1,3, Robin G. Avison¹, John C. Gore^1,2, Malcolm J. Avison^1,2

¹Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA; ²Radiology and Radiological Sciences, Vanderbilt Medical Center, Nashville, TN, USA; ³3MR Clinical Science, Philips Healthcare, Cleveland, OH, USA

                  961.       Relaxation Times of Human Basal Ganglia Regions at 7 Tesla

Oliver Kraff^1,2, Jean-Jacques Lemaire^3,4, Jens M. Theysohn^1,2, Mark E. Ladd^1,2

¹Erwin L. Hahn Institute for MRI, Essen, Germany; ²Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany; ³Equipe de Recherche en Imagerie Médicale, Univ. Clermont, Clermont-Ferrand, France; ⁴Service de Neurochirurgie A, Hôp G Montpied, CHU Clermont-Ferrand, Clermont-Ferrand, France

This study aimed to perform relaxation measurements (T1, T2, and T2*) of the basal ganglia regions. Datasets of ten healthy volunteers were acquired on a 7T whole-body MR scanner using an 8-channel head coil. T2* (multi-echo GRE), T2 (multi-echo SE), and T1 (dual-angle 3D-FLASH) maps were performed for the posterior (thalamic) region, whereas only T2* maps were realized for all three regions (pre-commissural, retro-commissural, and posterior) of the basal ganglia. Our results show the inhomogeneity of relaxation times at the different anatomic levels and may help in optimizing image contrast of deep brain nuclei of the basal ganglia.

                  962.       Atlas-Based Analysis of Human Brainstem Anatomy as Revealed by Gradient-Echo T2 Weighted MR Imaging at 7T

Fabrice Poupon^1,2, Dominique Hasboun³, Linda Marrakchi^1,2, Eric Bardinet⁴, Jean-François Mangin^1,2, Irina Kezele^1,2, Sarah Fernandez-Vidal⁵, Kamil Ugurbil⁶, Stéphane Lehericy⁷, Cyril Poupon^1,2, Pierre-François van de Moortele⁶, Jérôme Yelnik⁵

¹NeuroSpin, CEA, Saclay, France; ²IFR49, Paris, France; ³Groupe Hospitalier Pitié-Salpêtrière, Paris, France; ⁴CNRS-UPR 640, LENA, Paris, France; ⁵Inserm U679, Paris, France; ⁶CMRR, Minneapolis, USA; ⁷CENIR, Paris, France

Spatial resolution improved with ultra-high field MR systems, and new contrasts based on iron concentration help the segmentation of some mesencephalon structures which are of interest in Parkinson disease studies. Nonetheless, in a variant of Parkinson’s disease, smaller structures of the brainstem are involved. An experienced anatomist explored the brainstem structures by direct identification in a gradient-echo T2-weighted MRI at 7T. This identification was guided by two histological atlases: a 3D histological and deformable atlas of the basal ganglia comprising several structures of the mesencephalon and a numerized and reconstructed version of a printed atlas of the entire brainstem.

                  963.       3D Visualization of Deep Cerebellar Nuclei Using 7T MRI

Stefan Maderwald^1,2, Michael Küper³, Markus Thürling^1,3, Kasja Rabe^1,3, Oliver Kraff^1,2, Elke G. Gizewski^1,2, Mark E. Ladd^1,2, Dagmar Timmann³

¹Erwin L. Hahn Institute for MRI, Essen, Germany; ²Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany; ³Department of Neurology, University Hospital Essen, Essen, Germany

The results of the present study show that susceptibility weighted imaging (SWI) using 7T MRI allows structural imaging of the deep cerebellar nuclei in the submillimeter range. Each of the four cerebellar nuclei (dentate, emboliform, globose, and fastigial nuclei) can be identified in healthy subjects. This technique is envisaged to be useful in determining the localization and extent of cerebellar nuclei lesions with great precision in human cerebellar lesion studies.

                  964.       In-Vivo Quantification of the Hippocampal Subfields Using 4.7T Fast Spin Echo Imaging

Nikolai Vladimirovich Malykhin^1,2, Robert Marc Lebel¹, Nicholas J. Coupland³, Rawle Carter³, Peter Seres¹, Alan H. Wilman¹

¹Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada; ²Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada; ³Psychiatry, University of Alberta, Edmonton, Alberta, Canada

Changes in the hippocampus have often been implicated to the pathophysiology of many neurological and psychiatric diseases. Current MRI studies measure global hippocampal atrophy instead of measuring volume loss in its subfields. The purpose of this study was to delineate and quantify the hippocampal subfields in-vivo within entire hippocampal structure using ultra-high resolution Fast Spin Echo (FSE) imaging at 4.7T.

                  965.       Reliability Analysis of Hippocampal MRI Volumetry at 3 Tesla

Jacobus F.A. Jansen¹, Cecile R. Jeukens², Marielle C. Vlooswijk², H J. Majoie², Marc C. de Krom², Albert P. Aldenkamp², Paul A. Hofman², Walter H. Backes²

¹Department of Medical Physics & Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; ²Maastricht University Hospital, Maastricht, Netherlands

This work provides a detailed reliability analysis for hippocampal volumetry of T1-weighted MR images acquired at 3T. Two readers performed hippocampal volumetry on MR images of 40 patients with cryptogenic localization-related epilepsy and 20 healthy control subjects. Reliability measures and criteria to assess and ensure sufficient reliability were defined. Also, the validity of the correction for total intracranial volume size was critically assessed. The interreader reliability values were determined: intra-class-correlation-coefficient, ICC = 0.86 (left) and 0.86 (right), percentage volume difference VD = 7.4 ± 5.8 % (left) and 6.2 ± 4.8 % (right), and overlap ratio OR = 0.82 ± 0.04 (left) and 0.082 ± 0.03 (right). The positive Pearson correlation between hippocampal volume and total intracranial volume volumes was found to be low: r = 0.48 (p = 0.03, left) and r = 0.62 (p=0.004, right), showing the limited benefit of the brain size correction.

                  966.       In-Vivo Rat Brain Tissue Characterization by Susceptibility Weighted Imaging at 9.4 T

Nicoleta Baxan¹, Iulius Dragonu¹, Laura-Adela Harsan¹, Maxim Zaitsev¹, Jürgen Hennig¹, Dominik von Elverfeldt¹

¹Diagnostic Radiology, Medical Physics, University Hospital, Freiburg, Germany

Magnetic heterogeneity of brain tissue is caused by the venous vascular system (paramagnetic blood deoxyhemoglobin), by different tissue iron concentrations and tissue myelin content. These heterogeneities are the origin of contrast in susceptibility weighted imaging (SWI) since they induce an offset in the resonance frequency that can be detected in the signal phase. In this study SWI was used to improve contrast in rat brain regions of different magnetic susceptibilities by combining magnitude and phase information and to estimate, for the first time on animal models, frequency shifts occurred within and between white matter (WM) and gray matter (GM).

                  967.       A High-Resolution Quantitative Method for the Study of the Post Mortem Brain

Ana-Maria Oros-Peusquens¹, Fabian Keil¹, Miriam Rabea Kubach¹, N Jon Shah^1,2

¹Institute of Medicine, Juelich, Germany; ²Faculty of Medicine, Department of Neurology, RWTH Aachen University, Aachen, Germany

MRI-based investigations of the post mortem brain are relevant to brain mapping endeavours as well as to a better understanding of brain pathology. Both research directions, but in particular the latter, would benefit from the availability of quantitative data to characterise post mortem tissue. We report on the quantitative measurement of the whole post mortem brain with (0.54x0.54x0.6)mm3 using a 3D method which provides proton density, longitudinal and relaxation times maps. The primary source of contrast is due to the proton density M0, which is higher than in vivo. A strong shortening of the relaxation times is found, but T2* contrast between GM and WM is present. The T1 maps highlight specific structures, for example the stria of Gennari. It is expected that quantitative measurements on the post mortem brain will provide better insight into brain pathologies, especially upon comparison with histology.

                  968.       Could We Characterize Fine Structures in Human Brain Using High-Resolution Magnitude and Phase Image at 7 Tesla in Vivo?

Chan Hong Moon¹, Kyongtae Ty Bae^1,2

¹Radiology, University of Pittsburgh, Pittsburgh, PA, USA; ²Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA

Using the high-resolution magnitude and phase images, the vessel, neuronal fiber, or CSF surrouding artery could be identified.

                  969.       In Vivo Visualization of Cerebellar Cortical Layers Using Structural High Field MRI

José Pedro Marques¹, Wietske van der Zwaag¹, Cristina Granziera², Gunnar Krueger³, Rolf Gruetter¹

¹Centre d'Imagerie BioMédicale, CIBM, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Vaud, Switzerland; ²Department of Neurology and Radiology, Centre Hospitalier Universitaire Vaudois, CHUV, Lausanne, Vaud, Switzerland; ³Advanced Clinical Imaging Technology, Siemens Medical Solutions-CIBM, Lausanne, Vaud, Switzerland

The highly complex geometry and small size of the cerebellum make this area particularly attractive for very high-resolution imaging. With the use of a surface coil at 7T, human in-vivo cerebellum images with an in-plane resolution of 120µm were acquired. At this spatial resolution, ~240µm structures within the cerebellar cortex could be visualized. Using the image contrast of 30µm rat data acquired at 14T as a comparison, these structures could be identified as granule and molecular layers of the cerebellum.

                  970.       Morphometric MRI Analysis Based on High Resolution 3D Imaging at 7 Tesla Highlightes Focal Cortical Dysplasia in Epilepsy

Oliver Speck¹, Claus Tempelmann², Julia Matzen², Hans-Jürgen Huppertz³

¹Biomedical Magnetic Resonance, Otto-von-Guericke University, Magdeburg, Germany; ²Clinic for Neurology, Otto-von-Guericke University, Magdeburg, Germany; ³Swiss Epilepsy Center, Zurich, Switzerland

Few studies have evaluated the clinical potential of very high field strength. In many epilepsy patients, localization of the underlying epileptogenic lesion is difficult if not impossible with current imaging methods. Invasive EEG recordings are frequently required to delineate the epileptogenic zone. Recently, morphometric MRI analysis based on high resolution anatomical MRI has been proposed as a promising tool for the detection of small focal cortical dysplasia, a frequent cause of pharmacoresistent focal epilepsy. The purpose of this feasibility study was to test whether high resolution whole brain anatomical imaging at 7 Tesla can be used for fully automatic morphometric MRI analysis.

                  971.       Ultra-High Field Clinical Brain MR Imaging: Challenge and Excitement

William T.C. Yuh¹, Greg A. Christoforidis¹, Steffen Sammet¹, Petra Schmalbrock¹, Nina A. Mayr², John C. Grecula¹, Eric C. Bourekas¹, Jian Z. Wang², Jun Zhang¹, Michael V. Knopp¹

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

The purpose of this study to demonstrate and discuss the potentials, challenges and pitfalls of ultra-high field CNS imaging for various CNS pathologies based on our experiences in both 7 T and 8 T whole body human Magnetic Resonance scanners (MR). The implementation of ultra-high field whole body systems in the clinical setting provides many advantages and potentials for CNS imaging, and yet there are many technical and clinical challenges to be overcome.

                  972.       Ex Vivo Detection of Cerebral Amyloidosis on a Human 7 Tesla MRI System.

Sanneke van Rooden¹, Marion L.C. Maat-Schieman², Rob J.A. Nabuurs¹, Louise van der Weerd^1,3, Sjoerd G. van Duinen⁴, Remco Natte⁴, Mark A. van Buchem¹, Jeroen van der Grond¹

¹Radiology, Leiden University Medical Center, Leiden, Netherlands; ²Neurology, Leiden University Medical Center, Leiden, Netherlands; ³Anatomy, Leiden University Medical Center, Leiden, Netherlands; ⁴Pathology, Leiden University Medical Center, Leiden, Netherlands

Problem: We explore the ability of human 7T MRI to detect differences in the cortex of brain specimens with and without Aβ deposition.

                  973.       Parkinson’s Disease - Direct Visualization by 7.0T Brain Imaging

Se-Hong Oh¹, B. Jeon², Jong-Min Kim², Kyung-Nam Kim¹, Sung-Yeon Park¹, Dae-Hyuk Kwon¹, Young-Bo Kim¹, Z. H. Cho¹

¹Neuroscience Research Institute, Gachon University of Medicine and Science, Incheon, Nam-dong gu, Korea; ²Movement Disorder Center, Seoul National University Hospital, Seoul, Jong-ro Gu, Korea

An easily applicable diagnostic marker for Parkinson's disease (PD) is not yet available. To directly visualize substantia nigra (SN), mainly affected site in PD, we applied high resolution imaging by ultra high-field 7.0 Tesla MRI. T2*-weighted images clearly discerned the SN from surrounding areas such as the crus cerebri (CC) and red nucleus. In PD, the border between SN and CC appeared irregularly indented in striking contrast to that of normal individuals.

                  974.       Extremely High Resolution, High Field Imaging of Brain Iron in an Iron-Storage Disease

John Frederic  Schenck¹, Jeff H. Duyn², Peter van Gelderen², Hellmut Merkle², Arnulf E. Koeppen³, Jiang Qian, Earl A. Zimmerman³, John Cowan³, David L. Henderson

¹MRI Laboratory, General Electric Global Research, Schenectady, NY, USA; ²NINDS, National Institutes of Health, Bethesda, MD, USA; ³Albany Medical College, Albany, NY, USA

The rare genetic disorder aceruloplasminemia (aCp) is characterized by brain iron deposition 4-5 times that in normal brain and thereby permits a more detailed evaluation of brain iron distribution than can be performed in normal brains. We report the first high field (3T and 7T), high resolution MRI postmortem studies of an aCp brain. In addition to the usual pattern of brain iron deposition in the basal ganglia and related deep brain nuclei, this brain shows striking evidence for iron deposition in white matter and cortex and other regions not normally considered to contain iron. This suggests the possibility of increasing the brain regions where iron-dependent contrast can be used to study neurodegenerative diseases.

                  975.       High Resolution MRI of Xanthogranuloma of Choroid Plexus Induced by Hypercholesterolemia

Yuanxin Chen¹, John A. Ronald^2,3, Hagen Kitzler⁴, Andrew Alejski⁴, Kem A. Rogers⁵, Brian K. Rutt^4,6

¹Robarts Research Institute, London, Ontario, Canada; ²Robarts Research  Institute  , London, Ontario, Canada; ³University of Western Ontario  , London, Ontario, Canada; ⁴Robarts Research  Institute, London, Ontario, Canada; ⁵University of Western Ontario, London, Ontario, Canada; ⁶University of Western Ontario  , London , Ontario, Canada

High-resolution in vivo brain MRI reveals sizable xanthogranulomatous choroid plexus present in the hypercholesterolemic rabbits, which was confirmed by the histology and immunohistochemistry in these brains. FIESTA images show these masses as tumorous swellings of the choroid plexus with focal areas of hypointensity. The lesions mainly confined to the choroid plexus of lateral ventricle and the third ventricle accompanied by hydrocephalus and remarkable enlargement of the ventricular system. Histological studies show the lesions consisted characteristic foamy macrophages interspersed among prominent crystalline cholesterol clefts and lipid globules. These suggest that hyperlipemia/hypercholesterolemia may predispose to the formation of xanthogranuloma of the choroid plexus.

                  976.       A Study of Optimal Diffusion Indices to Differentiate Between Low and High Grade in Non-Enhancing Cerebral Gliomas and Neuronal- Glial Tumors

XIANG LIU¹, WEI TIAN², Sven Ekholm¹

¹Department of Radiology, University of Rochester Medical Center, Rochester, NY, USA; ²Department of Radiology, ; University of Rochester Medical Center, Rochester, NY, USA

Up to 40% non-enhancing supratentorial gliomas and neuronal-glial tumors may be misdiagnosed as low grade on conventional MRI. We hypothesized that diffusion indices from DTI are useful in preoperative grading of these tumors. The mean, maximal and mean maximal FA values and FA ratios as well as mean, minimal and mean minimal ADC values and ratios were evaluated in 25 patients. For all FA indices there were significant differences between low with high grade, ROC analysis showed that the mean maximal FA and maximal FA values had higher sensitivity and specificity in grading, which may be valuable supportive diagnostic tools.

                  977.       Imaging of Brain Metastases of Bronchial Carcinoma with 7 Tesla MRI

Christoph Moenninghoff^1,2, Stefan Maderwald^1,2, Philipp Schuett³, Jens M. Theysohn^1,2, Oliver Kraff^1,2, Mark E. Ladd^1,2, Thomas Gauler³, Michael Forsting^1,2, Isabel Wanke^1,2

¹Erwin L. Hahn Institute for Magnetic Resonance Imaging, University Duisburg-Essen, Essen, NRW, Germany; ²Department for diagnostic and interventional radiology and neuroradiology, University Hospital Essen, Essen, NRW, Germany; ³Department of Internal Medicine, Cancer Research, University Hospital Essen, Essen, NRW, Germany

The purpose of this work was to compare the depiction of brain metastases of bronchial carcinomas with susceptibility-weighted and contrast-enhanced MRI at 7T and 1.5T. Twelve patients underwent MR examinations with SWI and contrast-enhanced T1-weighted MPRAGE sequences at both field strengths using a higher spatial resolution at 7T. 7T SWI MIPs depicted 20 more microhemorrhages in 12 patients compared to 1.5T. Double-dose contrast-enhanced 7T versus 1.5T T1-weighted images depicted the same number of metastases in 6 patients, whereas single-dose enhanced 7T T1w sequences missed several micrometastases. Application of double-dose CA and the higher achievable spatial resolution and sensitivity for susceptibility artifacts of 7T MRI are beneficial for the depiction of brain metastases.

                  978.       Taurine – a Potential Natural Biomarker of Apoptosis in Gliomas

Kirstie S. Opstad¹, B Anthony Bell², John R. Griffiths³, Franklyn A. Howe²

¹Division of Basic Medical Sciences, St. George's, University of London, London, UK; ²Division of Cardiac and Vascular Sciences, St. George's, University of London, London, UK; ³Cancer Research UK Cambridge Research Institute, Cambridge, UK

Cancers survive by increased cellular proliferation, decreased cellular turnover and dysregulation of apoptosis. In vivo methods for monitoring early responses to novel apoptosis targeted therapies are required, and one potential modality is ¹H MRS. We have investigated whether there is a biochemical correlate to apoptosis in gliomas using HRMAS ¹H MRS and histology on the same human biopsy samples. Principal component analysis shows a pattern of metabolites and lipids that correlate with apoptosis in non-necrotic biopsies only. However, analysis of individual metabolites suggests the quantified taurine signal is a biomarker for tumor apoptosis that is independent of tumor necrosis.

                  979.       Predicting Response to Anti-Angiogenic Chemotherapy in Patients with High-Grade Glioblastomas Using MR Perfusion Imaging

Rahul Sawlani^1,2, Jeffrey Raizer, MD³, Sandra W. Horowitz¹, Wanyong Shin^1,2, Sean A. Grimm³, James P. Chandler⁴, Robert Levy⁴, Christopher C. Getch⁴, Maulin Shah^1,2, Timothy J. Carroll^1,2

¹Radiology, Northwestern University, Chicago, IL, USA; ²Biomedical Engineering, Northwestern University, Evanston, IL, USA; ³Neurology, Northwestern University, Chicago, IL, USA; ⁴Neurosurgery, Northwestern University, Chicago, IL, USA

Using MR perfusion imaging, the response to anti-angiogenic chemotherapy can be predicted for individual patients. In this study, we evaluated twelve patients with high-grade GBMs on a trial of Bevacizumab. For each patient, change in perfusion from before to after start of treatment was compared to the number of days to tumor progression.

                  980.       Multi-Source Feature Selection to Improve Multi-Class Brain Tumor Typing

Vangelis Metsis¹, Dionyssios Mintzopoulos^2,3, Heng Huang¹, Michael N. Mindrinos⁴, Peter M. Black⁵, Filia Makedon¹, A Aria Tzika^2,3

¹Computer Science, University of Texas, Arlington, TX, USA; ²NMR Surgical Laboratory, MGH & Shriners Hospitals, Harvard Medical School, Boston, MA, USA; ³Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, USA; ⁴Biochemistry, Stanford University School of Medicine, Palo Alto, CA, USA; ⁵Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

Recent trends in biomedical research have stressed the potential of combining more than one data sources to better understand a patient’s condition. We acquire state-of-the-art high-resolution magic angle spinning (HRMAS) proton (H1) Magnetic Resonance Spectroscopy (MRS) and gene expression date from the same brain tumor biopsies in order to identify and classify different profiles of brain tumors. We use a novel framework to perform heterogeneous data fusion on both MRS and gene expression datasets using machine learning algorithms. Our experimental results show that our framework outperforms any analysis using individual datasets.

                  981.       Age-Filtered MRS Classifier to Overcome the Differences in Childhood and Adulthood Brain Tumours

Javier Vicente¹, Juan Miguel García-Gómez¹, Salvador Tortajada¹, Elies Fuster-Garcia¹, Antoni Capdevila², Andrew Charles Peet³, Bernardo Celda⁴, Monserrat Robles¹

¹IBIME-ITACA, Universidad Politécnica de Valencia, Valencia, Spain; ²Hospital Sant Joan de Déu, Barcelona, Spain; ³Birmingham Children's Hospital NHS Foundation Trust, University of Birmingham, Birmingham, UK; ⁴Departamento de Química Física, Universidad de Valencia, Valencia, Spain

Several studies confirm that the nature of child Brain Tumours (BT) may be totally different from adults. We have developed classifiers for adulthood and childhood BT and compared performances with independent test sets of children and adult patients using 489 (93 children, 396 adults) SV 1H-MRS at 1.5T histopathologically diagnosed brain tumor cases. Performance dramatically lowered when children classifiers were tested with an adult test set and vice-versa. A filter based on the normal probability density function of the training dataset’s age can successfully overcome these differences and obtain a classifier that globally behaves as predicted by the training performance.

                  982.       Detection of Glycine as a Biomarker of Malignancy in Childhood Brain Tumours Using In-Vivo ¹H MRS at Short and Long TE

Nigel Paul Davies^1,2, Martin Wilson^1,3, Kal Natarajan^1,2, Yu Sun^1,3, Shaheen Lateef³, Lesley MacPherson³, Marie-Anne Brundler³, Theodorus N. Arvanitis^3,4, Richard G. Grundy⁵, Andrew Charles Peet^1,3

¹Cancer Sciences, University of Birmingham, Birmingham, UK; ²Imaging & Medical Physics, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK; ³Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UK; ⁴School of Electronic, Electrical & Computer Engineering, University of Birmingham, Birmingham, UK; ⁵Children's Brain Tumour Research Centre, University of Nottingham, Nottingham, UK

MRS provides a unique opportunity to study the metabolism of brain tumours non-invasively. Glycine is thought to be relevant in the metabolism of malignant brain tumours, but it is difficult to distinguish at low field from myo-inositol at around 3.6 ppm. LCModel analysis of short and long TE single-voxel MRS employing simulated basis sets has been used to quantify glycine in 48 childhood brain tumours in comparison with HR-MAS studies of biopsy samples. In vivo, glycine was found in medulloblastomas and glioblastomas but not in low grade astrocytomas, consistent with previous studies and in agreement with the HR-MAS results.

                  983.       Diagnosis of Brain Metastasis:Feasibility and Efficacy of Motion-Sensitized Driven-Equilibrium(MSDE) Turbo Spin-Echo Sequence

Eiki Nagao¹, Takashi Yoshiura¹, Akio Hiwatashi¹, Koji Yamashita¹, Hironori Kamano¹, Yukihisa Takayama¹, Osamu Togao¹, Makoto Obara², Tomoyuki Okuaki², Hiroshi Honda¹

¹Department of Clinical Radiology, Kyushu University, Fukuoka, Japan; ²Philips Electoronics Japan, Japan

In this study, a turbo spin-echo with a motion-sensitized driven-equilibrium (MSDE) sequence was used as an alternative head MR imaging technique for brain metastasis. We hypothesized that MSDE suppresses signals from flowing blood in vessels that can mimic the enhancement of brain metastases. Post-contrast images of 18 patients were analyzed. In each patient, images were obtained using three sequences: 3D MPRAGE, 3D turbo spin echo (TSE) without MSDE, and 3D TSE with MSDE. Our results suggest that MSDE effectively suppresses blood vessel signals from both arteries and veins, while TSE without MSDE suppresses signal from arteries only.

                  984.       DSC-MRI Measures of RCBV Predict Response to Bevacizumab Treatment More Reliably Than Standard MRI in Patients with Recurrent High-Grade Gliomas

Kathleen M. Schmainda^1,2, Devyani Bedekar¹, Scott D. Rand¹, Jennifer Connelly³, Shekar Kurpad⁴, Hendrikus G. J. Krouwer⁵, Eric S. Paulson⁶, Mark G. Malkin^3,4

¹Radiology, Medical College of Wisconsin, Milwaukee, WI, USA; ²Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA; ³Neurology, Medical College of Wisconsin, Milwaukee, WI, USA; ⁴Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA; ⁵Regional Cancer Center, Waukesha Memorial Hospital, Waukesha, WI, USA; ⁶Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA

The anti-VEGF (vascular endotholelial growth factor) antibody, bevacizumab, is in clinical testing for the treatment of gliomas with promising results. However, it is quickly becoming apparent that evaluation of response, using standard measures such as enhancing tumor volume or the extent of T2-weighted abnormalities on MRI, are often unreliable. In this study of recurrent high-grade glioma patients, treated with bevacizumab plus irinotecan, we demonstrate that DSC-derived measures of relative cerebral blood volume (rCBV) while similar to standard MRI for predicting response are much more reliable, early predictors of treatment failure and disease progression compared to standard MRI methods of evaluation.

                  985.       Evaluation of Treatment Response in Children with Brainstem Glioma by Correlating Cerebral Blood Flow Changes with Combined Vandetanib Administration and Local Radiation Therapy

Yong Zhang¹, Zoltan Patay¹, Ralf B. Loeffler¹, Ruitian Song¹, Alberto Broniscer², Claudia M. Hillenbrand¹

¹Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA; ²Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA

Pulsed arterial spin labeling was used to measure cerebral blood flow (CBF) changes in pediatric brainstem glioma patients treated with combined Vandetanib, a novel anti-angiogenesis drug, and local radiation therapy. Tumor CBF measured at the end of radiation therapy showed a negative correlation with the Vandetanib dose, indicating the efficacy of Vadetanib in inhibiting tumor vascularization. Marginally lower CBF in regions receiving 30 Gy of radiation and above in normal appearing brain parenchyma may point to radiation toxicity. These findings suggest that CBF seems to be a promising biomarker for monitoring treatment strategies that affect the vascularization of tumor tissue.

                  986.       Subclassification of Brain Tumors Based on Ex Vivo MRS Metabolic Profiles

Torill Eidhammer Sjøbakk^1,2, Sasha Gulati³, Michel Gulati¹, Steinar Lundgren^1,4, Sverre Helge Torp^5,6, Ingrid Susann Gribbestad¹

¹Dept. of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; ²St.Olavs University Hospital, Trondheim, Norway; ³Dept. of Neurosurgery, St. Olavs University Hospital, Trondheim, Norway; ⁴Dept. of Oncology, St. Olavs University Hospital, Trondheim, Norway; ⁵Dept. of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway; ⁶Dept. of Pathology and Medical Genetics, St.Olavs University Hospital, Trondheim, Norway

The main groups of brain tumors can be classified using MR spectroscopy. Subclassification of these groups could provide more unique and individual biological information of value for patient treatment. HR MAS MR spectra were obtained from tumor tissue samples from patients with brain metastases and meningiomas. Spin echo (TE 32) pulse spectra were examined using principal component analysis and partial least square regression analysis and compared with histopathological data. Using HR MAS metabolic profiles, a subclassification of meningiomas correlating to histopathological grading was found. The spectra of brain metastases showed a subgroup of malignant melanoma metastases.

                  987.       Short Echo Time ¹H Magnetic Resonance Spectroscopic Imaging in the Differentiation of High Grade Gliomas and Metastases in the Human Brain.

Jannie Petra Wijnen¹, Miriam W. Lagemaat², Patrick Krooshof³, Albert J.S. Idema⁴, Geert J. Postma³, Lutgarde C.M. Buydens³, Tom W.J. Scheenen¹, Arend Heerschap¹

¹Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Gelderland, Netherlands; ²Radiology, Radboud Universtiy Nijmegen Medical Centre, Nijmegen, Netherlands; ³Analytical Chemistry, Radboud University Nijmegen, Nijmegen, Netherlands; ⁴Neurosurgery, Radboud Universtiy Nijmegen Medical Centre, Nijmegen, Netherlands

In this study we investigated the presence of possible differences in metabolite levels in glioblastoma multiforme and metastase as observed by ¹H Magnetic Resonance Spectroscopic Imaging. Typical regions in and around the tumor of patients with a glioblastoma multiforme (14) and patients with a metastasis (9) were examined with a short echo time semi-LASER sequence at 3T. Significant differences between these tumor types were observed in relative mI+Gly levels and relative Cho levels in the peritumoral T2 hyperintense regions pointing to differences in intersitial pressure and tumor infiltration.

                  988.       "Brain Surface Motion Imaging" to Detect Adhesion Between Meningioma and Brain.

Toshiaki Taoka¹, Toshiaki Akashi¹, Toshiteru Miyasaka¹, Hiroyuki Nakagawa¹, Kaoru Myochin¹, Satoru Iwasaki², Kimihiko Kichikawa¹

¹Radiology, Nara Medical University, Kashihara, Nara, Japan; ²Radiology, Higashiosaka City General Hospital, Higashiosaka, Osaka, Japan

The purpose of this study is to evaluate the feasibility of the imaging method we developed to observe pulsatile motion of brain surface (“brain surface motion imaging”) for providing pre-surgical information about adhesion between meningioma and brain surface. “Brain surface motion imaging” is a method in which subtractions of images in systolic and diastolic phase of CSF/brain pulsatile motion are made. In the current study, prediction for brain/meningioma adhesion by “brain surface motion imaging” agreed with surgical findings in 83% of the cases. This imaging method seems to be feasible as providing presurgical information about brain/meningioma adhesion.

                  989.       MR Based Longitudinal Assessment of Pituitary Adenoma Growth Using Fully Automated Coregistration and Intensity Normalization

Kyrre E. Emblem^1,2, Dominic Holland³, Geir Ringstad⁴, John K. Hald⁴, Anders M. Dale^3,5, Atle Bjornerud^1,6

¹Department of Medical Physics, Rikshospitalet University Hospital, Oslo, Norway; ²The Interventional Centre, Rikshospitalet University Hospital, Oslo, Norway; ³Department of Neurosciences, University of California, San Diego, USA; ⁴Clinic for Imaging and Intervention, Rikshospitalet University Hospital, Oslo, Norway; ⁵Department of Radiology, University of California, San Diego, USA; ⁶Department of Physics, University of Oslo, Oslo, Norway

Lifelong monitoring of residual tumor growth in patients diagnosed with pituitary adenomas is essential for their continued care and in the decision making of further therapy. Detection of small changes in tumor size is challenging using visual inspection alone and is further complicated by lack of image registration of images acquired at different time-points. We have evaluated the use of a novel rigid-bogy coregistration and intensity normalization method applied to 3D MR images acquired at different time points. The method was found helpful in making the diagnosis and resulted in a change of diagnosis in 38% of the patients.

                  990.       Perilesional Area of Brain Tumors: A Longitudinal Diffusion Tensor Imaging Study

Kun-Hsien Chou¹, Hsuan-Hui Wang², Wan-You Guo³, Ming-Tak Ho⁴, Ming-Hsiung Chen⁵, Woei-Chyn Chu¹, Ching-Po Lin^2,6

¹Institute of Biomedical Engineering, National Yang Ming University, Taipei, Taiwan; ²Institute of Biomedical imaging and Radiological Sciences, National Yang Ming University, Taipei, Taiwan; ³Division of Neuroradiology, Taipei Veterans General Hospital, Taipei, Taiwan; ⁴Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan; ⁵Institute of Neurological Neurosurgery, Taipei Veterans General Hospital, Taipei, Taiwan; ⁶Institute of Neuroscience, National Yang Ming University, Taipei, Taiwan

Peritumoral signal abnormalities (PSA) of brain tumors contain varieties of tissues, and are categorized mainly to abnormal protons (vasogenic edema, gliosis) and/or tumor infiltration. In clinical experience, T2-weighted MR images are usually used to identify PSA in patients with tumors, even though the two types of signal abnormalities can still hardly be distinguished effectively up to date. In an attempt to circumvent this problem, a novel method was proposed and DTI was applied to differentiate the complex contents of PSA by reversibility. Differentiating tissue contents of PSA may facilitate tumoral delineation and therefore change the therapeutic strategy.

                  991.       The Value of Two-Dimensional Gradient Echo Imaging (2D-GRE) and Susceptibility Weighted Imaging (SWI) in the Assessment of Hemorrhagic Lesions in Diffuse Brainstem Gliomas Treated with Radiation and Antiangiogenic Therapy

Ulrike Löbel¹, Jan Sedlacik¹, Mehmet Kocak², Alberto Broniscer³, Claudia M. Hillenbrand¹, Zoltán Patay¹

¹Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA; ²Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA; ³Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA

Two-dimensional gradient-echo imaging and susceptibility-weighted imaging (SWI) enhance visualization of magnetically susceptible substances such as hemorrhage and calcification. In patients with diffuse pontine glioma treated with conformal radiation and vandetanib, an angiogenesis inhibitor, both techniques were compared regarding their accuracy and validity for detecting hemorrhagic lesions. Image analysis and interpretation were found to be more accurate and straightforward with SWI as fewer lesions were missed or misinterpreted. We found that both techniques benefited from the availability of phase images, especially for differentiation of hemorrhage from calcification. However, SWI will likely become the new gold standard for imaging magnetically susceptible substances.

                  992.       Accurate T1 and T2 Maps Obtained with IR-TrueFISP Calibrated by a Patient Driven Model

Ralf Berthold Loeffler¹, Song Wu², Nicole van Groningen¹, Zoltan Patay¹, John O. Glass¹, Matthew P. Smeltzer², Claudia Maria Hillenbrand¹

¹Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA; ²Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA

Quantitative IR-TrueFISP T1 and T2 maps are sensitive to variation in the RF excitation pulse. To overcome this problem we developed a model for the transformation of IR-TrueFISP derived relaxation parameters in a large patient data set toward gold standard reference signals by density-varying calibration functions fitted through a natural cubic spline. We were able to create a calibration function that transforms the IR-TrueFISP such that the fitting error between the conventional data and the IR-TrueFISP data became very small and showed almost no bias, especially for the T2 values, which are usually more error prone.

                  993.       Differentiation of Oligodendroglial Genotypes Using Perfusion Weighted Imaging and Proton MR Spectroscopy

Sanjeev Chawla¹, Sangeeta Chaudhary¹, Ali Nabavizadeh¹, Sumei Wang¹, Gurpreet S. Kapoor², Gocke Timothy², Donald M. O'Rourke², Elias R. Melhem¹, Harish Poptani¹

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

To differentiate molecular subtypes of oligodendrogliomas, perfusion weighted imaging and multivoxel proton magnetic resonance spectroscopic imaging (1H-MRSI) were performed on 23 patients who were classified into two groups: 1p or 1p and 19q deletion (Group I), and 19q deletion only or intact alleles (Group II). Regions of oligodendrogliomas were categorized into high CBV and low CBV regions using a threshold value of 1.5 for rCBV (CBV normalized with respect to contralateral white matter). 1H-MRSI indices were computed from these regions and compared between two groups. Cho/Cr was significantly higher in-group I oligodendrogliomas from regions of high CBV only compared to group II.

                  994.       Brain Tumor Classification Using a Novel H1 HRMAS MRS Method and Robust Algorithmic Classifiers

Dionyssios Mintzopoulos^1,2, Ovidiu C. Andronesi^1,2, Konstantinos D. Blekas³, Loukas G. Astrakas^1,4, Peter M. Black⁵, A. Aria Tzika^1,2

¹NMR Surgical Laboratory, MGH & Shriners Hospitals, Harvard Medical School, Boston, MA, USA; ²Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, USA; ³Computer Science, University of Ioannina, Ioannina, Greece; ⁴Medical Physics, University of Ioannina, Ioannina, Greece; ⁵Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

We developed a novel approach that combines robust classification strategies with a 2D, solid-state, H1 HRMAS MRS method, TOBSY (TOtal Through-Bond SpectroscopY), which maximizes the advantages of HRMAS. We employed a linear Support Vector Machine (SVM) classifier combined with the powerful and robust minimum redundancy/maximum relevance (MRMR) feature-selecting method resulting in highly accurate classification. A robust classification approach and a sensitive multidimensional MRS technique at high magnetic fields should improve in vivo characterization, typing, and prognostication of brain tumors, and assist in stratifying patients for appropriate therapeutic protocols and for monitoring new therapies.

                  995.       Serial Analysis of Imaging Parameters in Patients with Newly Diagnosed Glioblastoma Multiforme

Yan Li¹, Janine Lupo¹, Wei Bian¹, Jason C. Crane¹, Soonmee Cha¹, Susan Chang², Sarah Nelson^1,3

¹Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA; ²Department of Neurological Surgery, University of California, San Francisco, CA, USA; ³Department of Bioengineering, University of California, San Francisco, CA, USA

Glioblastoma Multiforme (GBM) is the most common and the most malignant type of primary brain tumor, resulting in a median survival of approximately one year. Our study of 30 patients with GBM indicated that both the extent of resection and response to therapy were significantly associated with survival. Areas with a relatively large region having breakdown of the BBB, restricted diffusion or large CBV at pre-RT had shorter TTP. There was a relatively large increase in the nADC within the T2ALL lesion for the patients who progressed early compared to patients who progressed at a later time. The increase in anatomic volumes and values of nADC are significantly correlated with progression.

                  996.       FID-Based T1-Weighted UTE Imaging of Human Brain at 3T

Yongxian Qian¹, Tiejun Zhao², Fernando E. Boada¹

¹Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA; ²R&D, Siemens Medical Solutions USA, Pittsburgh, PA, USA

This abstract presents an alternative way to produce 3D T1-weighted brain images in which signal decays of short-T2 tissues or components are minimized by performing ultra-short echo time (UTE) acquisitions on free induction decay (FID) signals, instead of gradient- or spin-echoes. Brain Images of healthy volunteers and tumor patients acquired on a clinical 3T MRI scanner were demonstrated, with some interesting findings observed on the patient’s images.

                  997.       Short Echo Time MR Spectroscopy of Brain Tumors: Grading of Cerebral Gliomas

Jan Weis¹, Patrik Ring², Tommie Olofsson³, Francisco Ortiz-Nieto¹, Johan Wikström¹

¹Dept. of Radiology, Uppsala University Hospital, Uppsala, Sweden; ²Dept. of Radiology, Karolinska Institute, Stockholm, Sweden; ³Dept. of Pathology, Uppsala University Hospital, Uppsala, Sweden

The sets of MR spectra (TE 30 ms) were acquired from normal brain and gliomas grade II, III and IV. LCModel’s spectral fits were normalized (L2-norm). Mean measured spectra (MS), mean spectra of macromolecules and lipids (ML) in the range 1.4–0.9 ppm and mean difference spectra (DS = MS - ML - Lac) were computed. Correlation analysis of the patient and mean normalized spectral amplitudes was used for classification of the tumors. It was found advantageous to perform analysis using DS spectra. The shape of the ML spectrum was found to be good marker to discriminate between glioma grades.

                  998.       Comparison Study of MR Perfusion Imaging and Diffusion Tensor Imaging in the Grading of Non-Enhancing Cerebral Gliomas

Xiang Liu¹, Wei Tian², Sven Ekholm¹

¹Department of Radiology, University of Rochester Medical Center, Rochester, NY, USA; ²Department of Radiology, ; University of Rochester Medical Center, Rochester, NY, USA

The pre-operative grading of non-enhancing gliomas is difficult on conventional MRI and very important as up to 40% could be malignant. The purpose of this study was to evaluate if PWI and DTI could improve the grading accuracy. 39 patients with pathology confirmed non-enhancing supratentorial gliomas were included. The maximal and the mean FA showed significant difference between groups, accompanying with sensitivity and specificity of 90% based on threshold of 0.243 and 0.141 respectively. However, there was no significant difference of maximal rCBV and mean ADC. The maximal and average FA are better surrogate markers in differentiating non-enhancing supratentorial gliomas.

                  999.       Hybrid Functional Diffusion and Perfusion Maps for Evaluation of Gliomas

Benjamin M. Ellingson^1,2, Devyani P. Bedekar^1,2, Mark G. Malkin^1,3, Scott D. Rand^1,2, Alastair Hoyt⁴, Jennifer Connelly³, Shekar N. Kurpad^1,4, Kathleen M. Schmainda^1,2

¹Translational Brain Tumor Program, Medical College of Wisconsin, Milwaukee, WI, USA; ²Department of Radiology, Medical College of Wisconsin, Milwaukee, WI, USA; ³Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA; ⁴Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA

A new technique was developed that combines voxel-by-voxel changes in apparent diffusion coefficient (functional diffusion maps) and relative cerebral blood volume (functional perfusion maps) to examine regions of hypercellularity and hypervascularity, respectively. Results showed spatially separated clusters of hypercellularity and hypervascularity with an average separation of around 2-cm. Trends in affected volumes revealed two distinct temporal patterns after treatment with bevacizumab: vascular-independent and vascular-coupled tumor growth, which likely represent two distinct populations of tumor cells: infiltrative cells that thrive in ischemic/hypoxic conditions (such as "stem-like" cells) and cells that proliferate largely in the presence of high blood volume, respectively.

                  1000.     Improved RCBV Calculation with Leakage Correction and First Pass Extraction

Xintao Hu^1,2, Kelvin Wong^1,3, Pamela New⁴, Stephen Wong^1,3

¹Department of Radiology, The Methodist Hospital Research Institute, Houston, TX, USA; ²Department of Automation, Northwestern Polytechnical University, Xi'an, ShaanXi, China; ³Department of Radiology, Weill Medical College of Cornell University, New York, NY, USA; ⁴Department of Neurosurgery, The Methodist Hospital, Houston, TX, USA

Contrast agent leaking into extravascular space leads to inaccurate rCBV measurement using DSC-PWI. The errors might be magnified with the accumulated effect during blood recirculation phase. We introduced a method to extract the first pass of contrast agent concentration time curve by decomposing the tissue residue function R(t) into first pass and recirculation. R(t) was deduced from deconvolution using least-absolute-deviation regularization, which has been proved to preserve the shape of R(t) while reducing baseline oscillation. The proposed method was evaluated in CBV calculation in a longitudinal follow-up study of GBM patients undergoing gene therapy.

                  1001.     Diagnostic Value of Brain Functional Imaging in the Assessment of Intraaxial Tumors

Jose Maria Mateos-Pérez¹, Juan Adan Guzmán de Villoria², Irina Vidal-Migallón¹, Manuel Desco^1,3

¹Medicina y Cirugía Experimental, Hospital General Universitario Gregorio Marañón, Madrid, Spain; ²Radiodiagnostico, Hospital General Universitario Gregorio Marañón, Madrid, Spain; ³Centro de investigación en red en salud mental (CIBERSAM), Madrid, Spain

                  1011.     MRI Characterization of a Focal Rat Brain Necrosis Induced by Interlaced Microbeam Radiation Therapy.

Raphael Serduc^1,2, Nicolas Pannetier³, Audrey Bouchet², Thierry Brochard², Thomas Christen³, Gilles Berruyer⁴, Jean Laissue⁵, Francois Esteve³, Chantal Remy³, Emmanuel Barbier³, Alberto Bravin², Géraldine Le Duc², Elke Brauer²

¹CERCO, CNRS, Toulouse, France; ²Imaging Group, ESRF, Grenoble, France; ³U836, INSERM, Grenoble, France; ⁴Scisoft Group, ESRF, Grenoble, France; ⁵Bern Institute of pathology, Bern, Switzerland

We developed here a new irradiation modality which produced a very high (200Gy) uniform radiation dose to a restricted target in the rat brain using interlaced synchrotron microbeam radiation therapy. A local extravasation of Gd-DOTA (starting at day 7) and significant increases in T2W and ADC after exposure were observed by MRI at D30. Three months after irradiation, the lesion still exhibited higher ADC values. These changes characterized a focal necrosis confined to the radiation target while normal tissues surrounding the lesion were spared. This new irradiation method could be useful for any brain lesions involving radiosurgery.

                  1012.     Assessment of Vascular Reactivity in Two Rat Brain Gliomas (C6 and RG2) by Blood Volume Fraction MRI During CO₂ Challenge and Correlation to Mature Vessels

Benjamin Lemasson^1,2, Nicolas Pannetier^1,3, Thomas Christen^1,3, Jan Warnking^1,3, Alexandre Krainik^1,3, Régine Farion^1,3, Christoph Segebarth¹, Olivier Duchamp², Chantal Rémy^1,3, Emmanuel L. Barbier^1,3

¹Inserm, U836, Grenoble, F-38043, France; ²Oncodesign Biotechnology, Dijon, France; ³Université Joseph Fourier, Grenoble Institut des Neurosciences, UMR-S836, Grenoble, F-38043, France

To identify differences in microvascular maturity between two orthotopic glioma rat models (C6 and RG2, which differ in angopoietin-2 expression), we compared modification of blood volume fraction during a CO2 challenge. Observed differences are in good agreement with structural microvascular maturation detected by immunohistology (pericyte coverage index). MRI vasoreactivity measurement might be an important biomarker in neurooncology to better understand microvascular physiopathology and improve medical treatment.

                  1013.     Avastin Alone or Combined to Campto® Reduces Local Blood Oxygen Saturation in an Orthotopic Human Glioblastoma Model (U87-MG) in Nude Rats

Benjamin Lemasson^1,2, Thomas Christen^1,3, Nicolas Pannetier^1,3, Régine Farion^1,3, Christoph Segebarth^1,4, Xavier Tizon², Peggy Provent², Philippe Genne², Emmanuel L. Barbier^1,3, Olivier Duchamp², Chantal Rémy^1,3

¹Inserm, U836, Grenoble, F-38043, France; ²Oncodesign Biotechnology, Dijon, France; ³Université Joseph Fourier, Grenoble Institut des Neurosciences, UMR-S836, Grenoble, F-38043, France; ⁴Université Joseph Fourier, Grenoble Institut des Neurosciences, UMR-S836, Grenoble,  F-38043, France

Glioma tumors are highly angiogenic, therapies directed against tumor vasculature or preventing angiogenesis have been developed. Monitoring changes in structural and functional microvasculature should help to evaluate the efficiency of these therapies. This study shows structural (Blood Volume fraction and Vessel Size Index) and functional (Blood Brain Barrier permeability and local Blood Oxygen Saturation) modification in response to an anti-angiogenic treatment used alone or combined to a chemotherapy on an orthotopic human glioma model (U87-MG) xenografted in nude rat. lSO2 seems to be a sensitive reporter of antiangiogenic therapeutic effect and to provide independent information from BVf, VSI and BBBpem.

                  1014.     Evaluating Treatment Response of Tumors with Temporal Diffusion Spectroscopy: Preliminary Results

Daniel C. Colvin¹, Mary E. Loveless¹, Mark D. Does¹, Zou Yue¹, Thomas E. Yankeelov², John C. Gore¹

¹Vanderbilt University Institute of Imaging Science, Nashville, TN, USA; ²Vanderbilt University Insitute of Imaging Science, Nashville, TN, USA

Diffusion-weighted MRI is a noninvasive imaging technique commonly used to quantify the rate of water diffusion within cancerous tissues. The apparent diffusion coefficient (ADC) in tissue reflects the influence of cellular membranes and subcellular organelles which serve to restrict the molecular motion. Consequently, measurements of ADC are sensitive to changes in tissue microstructure and therefore serve as a useful tool in evaluting tumor response to therapy. While conventional methods of measurement are capable of revealing changes in tumor cellularity, Oscillating Gradient Spin-Echo (OGSE) methods, which measure diffusion over much shorter time scales, reveal structural variations on an intracellular scale.

                  1015.     ¹H MAS NMR Spectroscopy of Metabolites and Lipids During Cell Growth Arrest Induced by Cisplatin in Cultured Rat Glioma BT4C Cells.

Ladan Mirbahai¹, Martin Wilson², Christopher S. Shaw, Carmel McConville², Roger D.G Malcomson³, Risto A. Kauppinen⁴, Andrew C. Peet²

¹ School of Sport and Exercise Sciences, University of Birmingham, Birmingham, West midlands, UK; ²School of Cancer Sciences, University of Birmingham, Birmingham, UK; ³Department of Histopathology, Birmingham Childern's Hospital NHS Foundation Trust, Birmingham, UK; ⁴Dartmouth Medical School, Hanover, NH, USA

The possibility of using the detected alterations in lipid and metabolite profiles as early biomarkers of cisplatin treatment, prior to appearance of morphological characteristics of apoptosis is suggested in this study. Lipid and metabolite alterations were investigated in cisplatin treated rat glioma cells by 1H MAS NMR spectroscopy. The presence of intracellular lipid vesicles was examined by TEM and Nile red staining. To determine cell viability status TB, H&E staining, and DAPI were used. The growth cycle stage was determined by flow cytometry. Lipid and metabolite alterations were detected at early stages after treatment when most cells appeared morphologically viable.

                  1016.     ¹H MRS Detected Mobile Lipids in Rodent Gliomas: Correlation with EPR Determined Tumour Oxygenation

S K. Hekmatyar¹, Timo Liimatainen², Neil Jerome¹, Nadeem Khan³, Harold M. Swartz³, Risto A. Kauppinen¹

¹Biomedical NMR Research Center, Dartmouth Medical School, Hanover, NH, USA; ²Center for Magnetic Resonance Research, University of Minnesota,, Minneapolis, MN, USA; ³EPR Center, Radiology, Hanover, NH, USA

¹H MR Spectroscopy detected lipids serve as biomarkers both for brain tumour classification and treatment monitoring. In the present study, two malignant rat glioma (9L and F98) models were used to examine tumour oxygenation (ptO₂) by electron paramagnetic resonance (EPR) and ¹H MR spectroscopic imaging to map the saturated lipids (1.3ppm) and lactate. Lipid 1.3ppm/creatine ratio was 2.5-times higher in F98 than in 9L glioma, but differences in lactate/Cr ratios were not detected. EPR showed ptO2 of 5.9±0.8 in F98 and 34.9±3.3 mm Hg in 9L. These data indicate association of ¹H MRS lipids with hypoxic tumour microenvironment.

                  1017.     MRI Characteristics of Primitive Neuroectodermal Tumors (PNETs) in a Spontaneous JCV T-Antigen Transgenic Mouse Brain Tumor Model at 7 Tesla

Feroze B. Mohamed¹, Harvey Hensley², Luis Del Valle³, Linda Knight, Chris Conklin, Kamal Khalili³, Scott H. Faro, Jennifer Gordon³

¹Radiology, Temple University, Philadelphia, PA, USA; ²Fox Chase Cancer Center; ³Neuroscience, Temple University

Medulloblastomas and primitive neuroectodermal tumors (PNETs), are highly cellular malignant primary brain tumors representing the most common solid tumors arising in children. Currently, to our knowledge, realistic animal models to study the in-vivo imaging characteristics of these tumors are lacking. In this work we have developed and studied the MR imaging characteristic of these PNET’s in a spontaneous JCV T-antigen transgenic mouse brain tumor model at 7 Tesla.

                 1018.     High Resolution 13C HR-MAS Spectroscopy Analysis of Different Brain Regions from Rats Bearing C6 Implanted Gliomas

Valeria Righi^1,2, Pilar Lopez-Larrubia², Luisa Schenetti³, Vitaliano Tugnoli⁴, Maria-Luisa Garcia-Martin^2,5, Sebastian Cerdan²

¹Department of Surgery, NMR Surgical Laboratory,MGH Harvard Medical School, Boston, Massachussetts, USA; ²Instituto  de Investigacion Biomedicas "Alberto Sols", Madrid, Spain; ³Departement of Chemistry, Università di Modena, Modena, Italy; ⁴Departement of Biochemistry, Università di Bologna, Bologna, Italy; ⁵RM Ntra. Sra. del Rosario, Madrid, Spain

We demonstrated that 13C High Resolution Magic Angle Spinning (HR-MAS) NMR is a useful tool to detect and quantify the 13C in cerebral metabolism and opening the way to investigate cerebral tissue heterogeneity within the microliter range. Recently, by using HR-MAS high quality 13C spectra from small tissue biopsies (10 mg) were obtained. Here, we report for the first time to our knowledge, a 13C HR MAS study of normal and diseased brain regions of rats bearing C6 gliomas implanted. The expression of the genes involved in the glycolytic metabolism was investigated in brain biopsies from the same cerebral regions.

                  1019.     Long-Term Antipsychotic Treatment Does Not Alter MRS Measures of Metabolite Levels in Normal Rat Brain

Diana M. Lindquist¹, R S. Dunn¹, Brian Zappia¹

¹Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA

                  1037.     Hemodynamic Scaling of FMRI-BOLD Signal Amplitude in Normal Aging

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

Vascular reactivity and resting CBF levels lead to inter-subject variability in fMRI-BOLD contrast during a neural task. This variability is exacerbated in an aging population. fMRI-BOLD studies were conducted in older and younger subject groups using a motor, cognitive and a breath hold task. Inter-subject BOLD signal response variability during motor task performance was largely vascular and may exacerbate BOLD signal amplitude variability in the elderly. However, cognitive task induced a BOLD signal amplitude variability that was largely neural, in both younger and older groups. These results suggest that age-related differences in BOLD signal during cognitive task performance, is principally a consequence of neural variability.

                  1038.     Age-Related Differences in FMRI During Weighted Arm Lifting

Joo-hyun Kim¹, Huijin Song¹, Jae-jun Lee¹, Seung-tae Woo¹, In-sung Kim¹, Moon-jung Hwang², Young-ju Lee², Yongmin Chang^1,3

¹Department of Medical & Biological Engineering, Kyungpook National University, Daegu, Korea; ²GE healthcare, Seoul, Korea; ³Department of Diagnostic Radiology and Molecuar Medicine, Kyungpook National University, Daegu, Korea

There has been no study of the effects of aging on the simple daily-life motor task such as forearm lifting with and without weight. The aim of this study was to investigate neural correlates of human brain between weighted and none-weighted arm lifting. Also we studied age-related alterations in normal aging brain when the task involves similar performance levels as in younger subjects.

                  1039.     White Matter Integrity and Cognitive Ageing: A Combined Diffusion Tensor and Magnetization Transfer MRI Study

Mark E. Bastin¹, Lars Penke¹, Catherine Murray¹, Susana Muñoz Maniega¹, Maria Valdes Hernandez¹, Alan Gow¹, Joanna M. Wardlaw¹, Ian J. Deary¹

¹University of Edinburgh, Edinburgh, Midlothian, UK

Here we present interim data from a unique cohort of subjects, termed the Lothian Birth Cohort 1936 (LBC1936). These subjects, who were born in 1936 and underwent cognitive testing in 1947 at age 11, are currently undergoing brain imaging and repeat cognitive testing in their early 70s. These data are used to test the hypothesis that white matter integrity, as measured by diffusion tensor and magnetization transfer MRI, is related to cognitive ability in youth and current age, and efficiency of the brain’s information processing.

                  1040.     Diffusion Tensor Imaging of Creativity in Normal Human Subjects

Rex E. Jung^1,2, Arvind Caprihan¹, Robert S. Chavez¹, Ranee A. Flores¹, Richard J. Haier¹

¹Mind Research Network, Albuquerque, NM, USA; ²Neurosurgery, University of New Mexico, Albuquerque, NM, USA

Creativity is defined as the production of something both novel and useful. We hypothesized inverse relationships between diffusion tensor imaging (DTI) and measures of divergent thinking and openness to experience. DTI and behavioral measures were obtained in 37 normal adults (age range 18-29). We found that fractional anisotropy (FA) of the right inferior-frontal fasciculus inversely predicted divergent thinking ( p = .004, r2 = .20), while left anterior thalamic radiation FA inversely predicted Openness to Experience (p = .001, r2 = 25). The results suggest possible downregulation of frontal functioning supporting creative capacity as hypothesized previously (Dietrich, 2007).

                  1041.     Fiber Tractography in Healthy Adolescents: An Automated Approach

Ryan L. Muetzel^1,2, Paul F. Collins¹, Bryon A. Mueller², Kelvin O. Lim², Monica Luciana¹

¹Department of Psychology, University of Minnesota, Minneapolis, MN, USA; ²Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA

Adolescent brain development has been studied using conventional imaging methods and, more recently, diffusion tensor imaging. Traditional fiber tracking analyses require manually defined seed regions, which can be labor-intensive and can also lead to rater bias. In the present study, we use a fully-automated tractography method to generate white matter tracts in a sample of 144 healthy individuals ages 9-23. Significant correlations between age and mean fractional anisotropy were observed in the cingulum bundle, inferior fronto-occipital fasciculus, and superior longitudinal fasciculus. The data suggest the method used is sensitive to the subtle age-related changes in white matter in this population.

                  1042.     Comparison of Neighborhood Tractography Methods for Segmenting White Matter Tracts in the Ageing Brain

Mark E. Bastin¹, Susana Muñoz Maniega¹, Jonathan D. Clayden², Amos J. Storkey¹, Laura J. E. Brown¹, Alasdair M J MacLullich¹

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

Tractography provides a promising tool for assessing white matter connectivity in old age. However, tractography output is usually strongly dependent on user-specified ‘seed points’. We have shown, however, that it is possible to segment the same fasciculus in groups of subjects using a method we term neighborhood tractography (NT). In addition to the original ‘heuristic’ NT approach, we have recently developed two new NT methods which create probabilistic tract-matching models using supervised and unsupervised learning techniques. Here we investigate which of these three NT methods performs best in segmenting tracts in the brains of a cohort of elderly subjects.

                  1043.     Brain Aging Patterns with ADC Histogram Analysis: A Large Scale and Wide Age Range Retrospective Study (767 Subjects, 15 Days-93.8 Years)

Osamu Sakai¹, Steven Kussman¹, Al Ozonoff², Koji Tanabe¹, Kaan Erbay¹, Memi Watanabe¹, Naoko Saito¹, Hernan Jara¹

¹Radiology, Boston University School of Medicine, Boston, MA, USA; ²Biostatistics, Boston University School of Public Health, Boston, MA, USA

Purpose: To study the age dependencies of apparent diffusion coefficient (ADC) histogram of the brain in the large and wide age ranged population. Also to develop peak and width ADC vs. age mathematical model valid over the full human lifespan. Methods: Brain data of 767 subjects (15 days-93.8 years) obtained by SS-DW-SE-EPI were segmented into the whole intracranial matter leading to ADC histograms. Results: ADC peak value, as well as histogram width of the whole brain showed clear age-related patterns. Conclusion: The mathematical models for ADC peak value and histogram width vs. age valid throughout life have been developed with 767 subjects.

                  1044.     Whole-Brain N-Acetylaspartate Concentration Comparison of Young and Elderly Healthy: Evidence for Brain Durability

William E. Wu¹, Oded Gonen¹, Juchen Hirsch², Lutz Achtnichts², Katherine Weir², Andreas U. Monsch², Achim Gass²

¹Radiology, New York University School of Medicine, New York, NY, USA; ²Neurology, University Hospital of Basel, Switzerland, Basel, Switzerland

The burden to healthcare delivery from the most common neurological disorders in the elderly is expected to become staggering. It is necessary, therefore to develop and validate non-invasive tools that can identify and quantify these disorders at their earliest – treatable stage. Since they affect primarily neurons, their MR-spectroscopic marker - N-acetylaspartate (NAA) is a probe and whole-brain NAA (WBNAA) can be the sought methodology, given that most neurological diseases are global. This study compares the WBNAA in a cohort of cognitively intact elderly versus young controls to quantify the effects of 30 years of aging on the brain’s NAA concentration.

                  1045.     Metabolic Profiling of the Posterior Cingulate Gyrus in Healthy Adults: A ¹H MRS Study

Sarah Andrea Wijtenburg^1,2, Kathleen L. Fuchs³, Virginia I. Simnad³, Jack Knight-Scott^1,2

¹Radiology, Children's Healthcare of Atlanta, Atlanta, GA, USA; ²Biomedical Engineering, University of Virginia, Charlottesville, VA, USA; ³Neurology, University of Virginia, Charlottesville, VA, USA

Here, we employ short TE ¹H MRS to investigate changes to cerebral metabolite concentrations in the posterior cingulate gyrus as a function of age and gender: healthy young (HY), healthy middle-aged (HM), and healthy elderly (HE). Choline (p=0.003, 87% power) was the only metabolite that exhibited any significant differences: HE and HM as well as HE and HY, and this effect was driven by changes in men.

                  1046.     Concentration Changes of Vitamin C and GSH in the Human Brain as Function of Age

Uzay Emrah Emir¹, Susan Raatz², Carolyn Torkelson², Tonya White², Susuan McPherson², Pierre-Gilles Henry², Melissa Terpstra²

¹University of Minnesota , Minneapolis, MN , USA; ²University of Minnesota, Minneapolis, MN, USA

Vitamin C (Asc) and glutathione (GSH) are the most concentrated chemical antioxidants in the central nervous system. These anti-oxidant concentrations may reflect the pathogenesis of progressive neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease, as well as cognitive decline.Double editing with (DEW) MEGA PRESS at high field has enabled noninvasive detection of these compounds in the human brain.This abstract presents preliminary findings on [Asc] and [GSH] as a function of age

                  1047.     Posterior Cingulate Metabolic Profile at Ultra-High Field Indicates Decreased Anti-Oxidative Capacity with Aging.

Mary Charlotte Stephenson¹, Antonio Napolitano², Maryam Abaei², Mirjam I. Schubert², Peter Gordon Morris¹, Dorothee P. Auer²

¹SPMMRC, School of Physics and Astronomy, University of Nottingham, Nottingham, UK; ²Academic Radiology, Queens Medical Centre, University of Nottingham, Nottingham, UK

Metabolic profiles in the posterior cingulate have been shown to be altered due to healthy aging, development, and disease. The purpose of the experiment was to observe changes in metabolic profiles, using a sequence optimized for observation of coupled metabolites at ultra-high field, in order to characterize changes in healthy aging. Decreases in N-acetyl aspartate and glutamate indicate brain atropy with aging, whereas decreases in Glu/Cr with constant NAA/Cr indicate perturbed metabolism with age. Decreases in Taurine with increases in Guanidinoacetate indicate reduced ability of the aged brain to deal with oxidative stress.

                  1048.     MCMxxxVI (1936): A New Versatile Automatic Technique for Brain Lesion Segmentation and Volume Analysis

Maria Valdes Hernandez¹, Mark E. Bastin², Joanna M. Wardlaw¹

¹Clinical Neurosciences, University of Edinburgh, Edinburgh, UK; ²Medical Physics, University of Edinburgh, Edinburgh, UK

We describe an alternative approach to automatically segment brain tissues, haemosiderin deposits (HDs) including brain microbleeds (BMBs) and white matter lesions (WMLs). Two types of structural images are registered, modulated in frequency to the red/green space and fused. Minimum variance quantization quantifies and segments tissues and lesion volumes. The intra-observer reliability and intra-class correlation coefficient for WMLs segmentation was 0.99, with a similarity index of 0.9. HDs and BMBs are all detected along with high-iron-content areas like small vessels. This approach is fast, accurate, observer independent and increases the reliability and repeatability of WML, BMBs and HDs volume measurements.

                  1049.     Volumetric Measurement of Multispectral Brain MRI : Based on Independent Component Analysis and Support Vector Machine

Clayton Chi-Chang Chen¹, Jyh-Wen Chai¹, San-Kan Lee¹, Yen-Chieh Ouyang², Chein-I Chang³, Wu-Chung Shen⁴, Hsian-Min Chen⁴

¹Department of Radiology, Taichung Veterans General Hospital, Taichung, Taiwan; ²Department of Electrical Engineering, National Chung Hsing University, Taichung, Taiwan; ³Remote Sensing Signal and Image Processing Laboratory, Department of Computer Science and E.E., University of Maryland, Baltimore County, USA; ⁴Department of Radiology, China Medical University Hospital, Taichung, Taiwan

Independent component analysis implemented with support vector machine has the advantages of using an unsupervised technique to separate the distinct objects and then followed by a supervised classification technique to perform target substance discrimination. The method could be effective in image analysis of the major components of normal and diseased brain in multispectral MRI. However, there was a lack of comprehensive assessment of the proposed method for brain segmentation in the clinical applications. In this study, we tried to carry out an experiment to test the accuracy and reproducibility of the proposed method in the synthetic and clinical MRI data.

                  1050.     Morphometry of the Corpus Callosum: Comparing Male Orchestral Musicians and Non-Musicians

Vanessa A. Sluming¹, Ihssan Adeeb Abdul-Kareem¹, Marta Garcia-Finana², Patricia E. Cowell³

¹Health Sciences, University of Liverpool, Liverpool, Merseyside, UK; ²Centre for Medical Statistics and Health Evaluation, University of Liverpool; ³School of Human Communication Sciences, University of Sheffield

Corpus callosum (CC) is considered to be the “information superhighway” between the cerebral hemispheres and has shown differences in cross-sectional area between musicians and non-musician. We investigated CC morphometry between male orchestral musicians and non-musicians using a technique addressing regional CC anatomy and shape to advantage. In posterior part of CC (widths cluster W89-94), string-playing musicians showed larger cluster relative to non-musicians which we interpret as supporting visuospatial cognition, notably sight reading ability, essential for orchestral musical performance, through increasing connections between visual and language regions. Lack of significant findings in clusters within anterior parts of CC contradicts earlier studies.

                  1051.     Sex Differences in the Neuroanatomy of Human Mirror-Neuron System: A T1-VBM Investigation

Kun-Hsien Chou¹, I-Yun Chen², Pei-Chin Chen³, Ya-Wei Cheng², Jean Decety⁴, Ching-Po Lin^2,3

¹Institute of Biomedical Engineering, National Yang Ming University, Taipei, Taiwan; ²Institute of Neuroscience, National Yang Ming University, Taipei, Taiwan; ³Institute of Biomedical Imaging and Radiological Sciences, National Yang Ming University, Taipei, Taiwan; ⁴The University of Chicago, Departments of Psychology and Psychiatry, Chicago, USA

Females frequently perform better in interpersonal sensitivity than males. The mirror-neuron-system (MNS) has been proposed to play an important role in social cognition. It remains to be clarified whether the neuroanatomy of MNS exhibits sex differences. With the use of T1-VBM concurrent with the dispositional empathy measures, we demonstrate that females had larger gray matter volume in the pars opercularis and inferior parietal lobule than males. Moreover, self-report scores in the emotional empathic disposition was correlated with gray matter volume of the pars opercularis across all participants. These results indicate that the existence of neuroanatomical sex differences in the MNS.

                  1052.     The Menopause May Be Associated with Hippocampal Volume Reduction

Masami Goto¹, Osamu Abe², Sachiko Inano², Tosiaki Miyati³, Naoto Hayashi⁴, Shigeki Aoki⁵, Harushi Mori², Hiroyuki Kabasawa⁶, Kenji Ino¹, Keiichi Yano¹, Kyouhito Iida¹, Kazuo Mima¹, Kuni Ohtomo²

¹Radiological Technology, University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan; ²Radiology, University of Tokyo, Bunkyo-ku, Tokyo, Japan; ³Graduate School of Medical Science, Kanazawa University, odateno, Kanazawa, Japan; ⁴Computational Diagnostic Radiology and Preventive Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan; ⁵Radiology, Juntendo University, Bunkyo-ku, Tokyo, Japan; ⁶Japan Applied Science Laboratory , GE Yokogawa Medical Systems, Ltd , Hino-shi, Tokyo, Japan

Lord et al. studied the relation between estrogen therapy and hippocampal volume in estrogen therapy users, past users, never users, and men, and suggested a positive association between estrogen and hippocampal volume [1]. In the present study, a significant decrease in gray matter volume was found in the hippocampus bilaterally in the postmenopausal group compared with the premenopausal group. The results of the current study suggest that the decreased release of estrogen in menopausal women may be associated with hippocampal volume reduction.

                  1053.     DIR Imaging Using Compressed Sensing for Cortical Thickness Estimation

Sung-Min Gho¹, Eung-Yeop Kim², Hahnsung Kim¹, Dong-Hyun Kim^1,2

¹Electrical and Electronic Engineering, Yonsei University, Shinchon-Dong, Seoul, Korea; ²Radiology, Yonsei University, Shinchon-Dong, Seoul, Korea

DIR has shown the potential for volumetric study through gray matter imaging. By suppressing cerebrospinal fluid and white matter and by using a fast spin echo based acquisition, cortical thickness measurements near air-bone interfaces could be obtained with reduced susceptibility artifacts compared with the standard MP-RAGE sequence. One drawback however with the DIR acquisition is the long scan time needed to acquire the full 3D data set. Here, work on combining DIR imaging with the compressed sensing algorithm is presented.

                  1054.     Quantifying Typical Cortical Thickness Development in Children

David C. Carver^1,2, Qing Ji¹, John O. Glass¹, Deqing Pei³, Wilburn E. Reddick¹

¹Translational Imaging Research, St. Jude Children's Research Hospital, Memphis, TN, USA; ²Physics and Astronomy, East Tennessee State University, Johnson City, TN, USA; ³Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA

This project developed models of typical cortical thickness development in children to serve as a benchmark for direct comparison with cancer survivors. We analyzed 140 typical subjects (70 male, 70 female) ages 5-18 with FreeSurfer. Models were generated for each cortical region using a mixed-effects polynomial regression model testing for cubic, quadratic and linear age effects using a step-down selection procedure. Subjects showed steady rates of decrease in cortical thickness with age. The developed models can now be used to compare with survivors of childhood cancer. In addition, the longitudinal models will be made publicly available.

                  1055.     Is B1-Correction for Neuroanatomy Necessary?

Jeff Gunter¹, Gregory Preboske¹, Chad Ward¹, Prashanthi Vemuri¹, Matt Bernstein¹, Clifford Jack,Jr¹

¹Radiology, Mayo Clinic, Rochester, MN, USA

For large clinical trials on-scanner B1-correction may not be assumed. Is it worth acquiring additional scans to do off-line B1 correction or are other post-processing methods sufficient?

                  1056.     Simulation of MRI Related Tissue Changes Occurring During Formaldehyde Fixation of Human Brain Hemispheres

Robert J. Dawe¹, David A. Bennett², Julie A. Schneider², Konstantinos Arfanakis¹

¹Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA; ²Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA

Postmortem MRI of the human brain allows for invasive examination of the tissue specimen immediately following the MR scan, a practice that is not possible with living subjects. However, previous investigations have shown that MR properties of the tissue vary with both time and position as fixation progresses, causing misinterpretation of MRI results. In this study, computer simulation was used to model the fixation process in cadaveric brain hemispheres immersed in formaldehyde solution. The resulting changes in the simulated T2 values were shown to be in reasonable agreement with previous experimental observations.

                  1057.     Slower Transverse Relaxation in the Dominant Hemisphere

Jianli Wang¹, James R. Connor², Qing X. Yang^1,2

¹Radiology, Penn State College of Medicine, Hershey, PA, USA; ²Neurosurgery, Penn State College of Medicine, Hershey, PA, USA

Most of time, our two cerebral hemispheres have different functions and usually one side dominates over the other on some specific functions. It is not clear whether there is any difference in the brain tissue relaxation time between the two hemispheres. The characterization of hemispheric symmetry of transverse relaxation rate, R2 (1/T2), in a specific anatomic structure in the normal human brain is important baseline information for clinical applications of T2-weighted imaging and quantitative parametric mapping. In this abstract, we report the hemispheric difference of T2 relaxation in a large normal human brain cohort at 3.0 T.

                  1058.     Temporal Progression of Thalamic Plaques in Alzheimer’s Disease Transgenic Mice (TAS10, TPM, TASTPM) – Comparison of MRI and µCT

Andreas Pohlmann¹, Fatima Alarakhia², Brian P. Hayes³, Victor Musoko⁴, Marion J. Perren⁵, D Ceri Davies², Michael F. James⁴

¹Academic DPU, GlaxoSmithKline R&D Ltd, Cambridge, UK; ²Imperial College London, London, UK; ³Respiratory CEDD, GlaxoSmithKline R&D Ltd, Stevenage, UK; ⁴Immuno-Inflammation CEDD, GlaxoSmithKline R&D Ltd, Harlow, UK; ⁵Neuroscience CEDD, GlaxoSmithKline R&D Ltd, Harlow, UK

In Alzheimer’s disease transgenic mice a co-accumulation of calcium and ferrous iron in some thalamic amyloid plaques has been demonstrated, which co-localise with T2* hypointensities (THIs). We studied THI development with age and its correlation with calcium deposition using MRI and µCT. The age-related growth of THIs differed significantly between genotypes but followed a similar trend in MRI and µCT. THI volumes in µCT and MRI correlated well and all but very small THIs were visualised by µCT. Further characterization of THIs is necessary, but these findings may shed light on the pathogenesis of Alzheimer’s disease.

                  1059.     The Effects of Genotype and Age on Fractional Anisotropy and Learning in an Alzheimer's Mouse Model

Jason C. Pych¹, Alice M. Wyrwicz¹

¹Center for Basic MR Research, NorthShore University Healthcare, Evanston, IL, USA

                  1060.     Perfusion and Diffusion Imaging in a Mouse Model of Alzheimer's Disease

Eric Raymond Muir^1,2, Jeromy Dooyema³, Lary C. Walker^3,4, James J. Lah^4,5, Timothy Q. Duong²

¹Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA; ²Research Imaging Center, University of Texas Health Science Center, San Antonio, TX, USA; ³Yerkes National Primate Research Center, Emory University, Atlanta, GA; ⁴Neurology, Emory University, Atlanta, GA; ⁵Center for Neurodegenerative Disease, Emory University, Atlanta, GA

Alzheimer's disease is a neurodegenerative disorder characterized by a decline in memory, cognitive function and cerebrovascular dysfunction. In this study we used a presenilin-1/amyloid precursor protein (PS/APP) transgenic mouse model of AD to assess perfusion and diffusion MRI methods that could be useful in detecting and studying AD. We utilized a recently developed cardiac spin labeling (CSL) technique to image basal cerebral blood flow and hypoxia-induced blood oxygen level dependent (BOLD) and CBF changes in PS/APP mice. Additionally, diffusion tensor imaging was performed to image apparent diffusion coefficient and fractional anisotropy in PS/APP and control mice.

                  1061.     Monitoring Therapy in a Triple Transgene Model of Alzheimer's DIsease Using MRS, Histology and Behavioral Correlations

Bruce G. Jenkins¹, Ji-Kyung Choi¹, Alpaslan G. Dedeoglu^2,3

¹Radiology, Massachusetts General Hospital, Charlestown, MA, USA; ²School of Medicine, Boston University, Boston, MA, USA; ³Neurology, Boston VA Hospital, Boston, MA, USA

Using a triple transgene model of AD including A-beta and tau pathology we found that treatement with the NSAID flurbiprofen produced reductions in elevated glutamine and protection of learning and tau pathology. There were significant correlations of glutamate values with learning and significant correlations of glutamine with histopathological markers of neurofibrillary tangles.

                  1062.     Deformation Based Morphometry in a Rodent Model of Parkinson's Disease

Anthony Christopher Vernon¹, Saga Johansson¹, William R. Crum², Michel Modo¹

¹Neuroscience, Institute of Psychiatry, Kings College London, London, UK; ²Centre for Neuroimaging Science, Institute of Psychiatry, Kings College London, London, UK

Imaging research for Parkinson’s disease (PD) has focused on identifying sensitive methods to assess nigrostriatal degeneration. Herein, we used longitudinal T2-weighted magnetic resonance imaging (MRI) with manual segmentation and deformation based morphometry (DBM) analysis to identify regional brain volume changes in a rodent in vivo model of PD. Significantly reduced striatal volume and lateral ventricular enlargement were detected 1,3 and 5 weeks post-lesion, when rats exhibited hemi-parkinsonian behavioural deficits. Unbiased DBM analysis revealed additional significant volume changes in globus pallidus and neocortex. These data suggest MRI volumetric measures could be used to monitor disease progression in this rodent PD model.

                  1063.     Progressive Neuroanatomical Changes in the YAC128 Mouse Model of Huntington’s Disease

Jason Philipp Lerch¹, Jeffrey B. Carroll², Matthijs van Eede¹, Michael R. Hayden², R. Mark Henkelman¹

¹Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada; ²Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada

We investigated the YAC128 mouse model of Huntington's Disease at 8 and 12 months of age using high-resolution MRI and found progressive atrophy in the striatum. The sensorimotor cortex, on the other hand, was thicker in YAC128 mice at 8 months of age but thinner than wild-type controls at 12 months, suggesting a potential compensatory mechanism in early stages of the disease.

                  1064.     MRI and MRSI Characterization of the Quinolinic Acid Lesion Model of Huntington's Disease Over 49 Days: Persistence of Low Apparent Diffusion Coefficients and Spontaneous Recovery of N-Acetyl Aspartate Levels

Noam Shemesh¹, Ofer Sadan², Eldad Melamed³, Daniel Offen³, Yoram Cohen¹

¹School of Chemistry, Tel Aviv University, Tel Aviv, Israel; ²Laboratory of Neurosciences, FMRC, Rabin Medical Center, Sackler School of Medicine , Tel Aviv University, Tel Aviv, Israel; ³Laboratory of Neurosciences, FMRC, Rabin Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

We characterized the spatial and temporal evolution of the Quinolinc acid (QA) lesion using T2 and diffusion weighted images (WI), and MRSI performed on days 1, 8, 25 and 49 post-QA injection. On day 1, a marked affected area was viewed as hyperintensity by the T2WI. On day 49, the apparent diffusion coefficient (ADC) maps from the striatum revealed areas characterized by both high and low ADCs, which correlated to necrotic regions and dense macrophage regions respectively. Normalized N-Acetyl-Aspartate levels revealed a statistically significant spontaneous recovery from 0.67±0.15 of the contralateral value on day 1 to 0.90±0.12 on day 49.

                  1065.     Intracellular PH Is a Promising Biomarker of Early Neurodegeneration, as Shown by ³¹P MRS in a 3-NP Rodent Model of Huntington's Disease

Myriam Marianne Chaumeil^1,2, Celine Baligand³, Emmanuel Brouillet², Philippe Hantraye², Pierre Carlier³, Vincent Lebon^1,2

¹CEA-NeuroSpin, Gif-Sur-Yvette, France; ²CEA-MIRCen, Fontenay-aux-roses, France; ³Association Institut de Myologie, Paris, France

To investigate whether cerebral pH can serve as an early biomarker of neurodegeneration, we conducted a study on a rat model of Huntington’s disease (n=5, chronic intoxication using 3-NP). Cerebral pH was measured at D0, D1, D3 and D5 post-intoxication using a ³¹P-PRESS sequence. T2-weighted imaging was performed to detect cerebral lesions. This study shows a significant increase in cerebral pH before the onset of striatal lesions (pH_D0=7.08±0.03 vs. pH_D3=7.17±0.02). Furthermore, pH variations are shown to correlate with SDH inhibition (p<0.05). Consequently, cerebral pH appears to be a relevant early biomarker of neurodegeneration, reflecting precocious metabolic changes.

                  1066.     Reduced T2 Reveal Therapeutic Effect of the Antioxidant Vitamin E in the G93A-SOD1 Mouse Model of ALS

Selina Bucher^1,2, Heiko G. Niessen³, Thomas Kaulisch⁴, Michael Neumaier³, Albert C. Ludolph¹, Detlef Stiller³

¹Department of Neurology, University of Ulm, Ulm, Germany; ²Department of Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany; ³In-Vivo Imaging Unit, Department of Drug Discovery Support, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany; ⁴In-Vivo Imaging Unit, Department of Drug Discovery Support, Boehringer Ingelheim Pharma GmbH & Co. KG,, Biberach, Germany

We investigated the effects of a preclinical antioxidant treatment with vitamin E on T2 relaxation time in order to evaluate if T2 is a sensitive non-invasive biomarker for the assessment of therapeutic approaches in the G93A-SOD1 mouse model of amyotrophic lateral sclerosis (ALS). A clear benefit of Vitamin E treatment for a significantly reduced ALS progression was shown in the study by means of MRI and validated by histology. In more general terms, it was shown that the measurement of the relaxation time T2 enables for a longitudinal non-invasive evaluation of therapeutic approaches in the G93A-SOD1 mouse model of ALS.

                  1067.     Diffusion Tensor Imaging of ALS-PDC at 21.1 T:  in Utero Vs ex Utero Exposure

Timothy Michael Gould^1,2, Jens Throvald Rosenberg^1,2, Ihssan Sabri Masad^1,2, Yemi Banjo³, Christopher A. Shaw^3,4, Samuel Colles Grant^1,2

¹Chemical & Biomedical Engineering, Florida State University, Tallahassee, FL, USA; ²National High Magnetic Field Laboratory, Tallahassee, FL, USA; ³Program in Neuroscience, University of British Columbia, Vancouver, BC, Canada; ⁴Ophthalmology, Physiology, and Experimental Medicine, University of British Columbia, Vancouver, BC, Canada

A variant environmental form of Amyotrophic Lateral Sclerosis (ALS) pathology called ALS-Parkinsonian Dementia Complex (ALS-PDC or Guamanian ALS) is introduced by administration of purified sterol β-D-glucoside (BSSG) in utero and ex utero. Excised brain and spinal cord specimens were analyzed by DTI at 21.1-T to generate fractional anisotropy (FA), apparent diffusion coefficient (ADC), and volumetric tractography data. Our analysis shows that ex utero administration exhibits significantly high ADC in the spinal cord white matter tracts and substantia nigra. These findings suggest that higher-grade ALS-PDC neuropathogenesis will result if individuals are exposed to BSSG after birth.

                  1068.     Increases in Creatine Detected by MRS Utilizing a Macaque Model of NeuroAIDS Suggests Glial Activation and Inflammation

Eva-Maria Ratai¹, Jeffrey Bombardier¹, Chan-Gyu Joo¹, Julian He¹, Lakshman Annamalai², Susan V. Westmoreland², Tricia H. Burdo³, Jennifer H. Campbell³, Caroline Soulas³, 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

Proton magnetic resonance spectroscopy has emerged as one of the most informative neuroimaging methods for the study of neuroAIDS as it provides surrogate markers to assess disease progression and monitor therapeutic treatment. Changes in N-Acetylaspartate (NAA) and NAA/creatine (NAA/Cr) are established markers of neuronal injury/loss. However, the biochemical basis of creatine alterations is less well understood. Utilizing the accelerated macaque model of neuroAIDS, we find increases in Cr during disease progression and hypothesize that these changes are related to increased energy demand due to astrocytosis and gliosis as a consequence of SIV infected monocytes entering the brain.

                  1069.     7 Tesla MR Spectroscopy Reveals That CD8 T Lymphocyte Depletion Alone Has No Effect on Brain Metabolite Concentrations Confirming the Accelerated Rhesus Macaque Model of NeuroAIDS

Eva-Maria Ratai^1,2, Sarah Pilkenton^1,2, Jeffrey Bombardier¹, Chan-Gyu Joo^1,2, Katherine W. Turk¹, Margaret R. Lentz^1,2, Julian He^1,2, Lakshman Annamalai^2,3, Shawn O' Neil^2,3, Susan V. Westmoreland^2,3, Tricia H. Burdo⁴, Jennifer H. Campbell⁴, Caroline Soulas⁴, Patrick Autissier⁴, Woong-Ki Kim⁵, Kenneth Williams⁴, R. Gilberto Gonzalez^1,2

¹Radiology, Massachusetts General Hospital - A.A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA; ²Harvard Medical School, Boston, MA, USA; ³New England Regional Primate Research Center, Southborough, MA, USA; ⁴Biology Department, Boston College, Boston, MA, USA; ⁵Eastern Virginia Medical School, Norfolk, VA, USA

SIV infection followed by CD8 lymphocyte depletion produces rapidly progressing neuro-AIDS that is characterized by consistently declining levels of N-acetyl-aspartate/creatine (NAA/Cr). This model makes possible the definitive testing of neuroprotective drugs within 3 months in as few as 4 animals. However, it remains unknown whether CD8+ depletion alone has an effect on cerebral metabolism. To answer this question, four rhesus macaques were examined by 7T 1H MR spectroscopy before and biweekly after CD8 depletion for 8 weeks. Data were compared to SIV infected CD8 depleted animals and revealed that CD8 depletion alone has no effect on brain metabolite concentrations.

                  1070.     Viral Burden and AIDS-Related Neurodegeneration: The Role of Blood and Cerebrospinal Fluid

Jeffrey P. Bombardier¹, Eva-Maria Ratai^1,2, Chan Gyu Joo^1,2, Jeffrey D. Lifson³, Michael Piatak, Jr³, Elkan Halpern¹, Susan V. Westmoreland⁴, Lakshmanan Annamalai⁴, Kenneth Williams⁵, Ramon Gilberto Gonzalez^1,2

¹Radiology, Massachusetts General Hospital, Charlestown, MA, USA; ²Radiology, Harvard Medical School, Charlestown, MA, USA; ³AIDS and Cancer Virus Program, SAIC-Frederick, National Cancer Institute, Frederick, MD, USA; ⁴New England regional Primate Research Center, Harvard Medical School, Southborough, MA, USA; ⁵Biology, Boston College, Chestnut Hill, MA, USA

We tested the hypothesis that brain injury is more closely related to SIV levels in blood rather than in cerebrospinal fluid. Neuronal injury was quantified by measuring N-acetylaspartate (NAA) levels with 1H-MRS in an accelerated SIV-infected macaque model of neuroAIDS. We found that NAA/Cr is correlated to the peripheral blood viral burden, and not to the viral levels in the CSF at later time points. This supports the theory that brain injury is primarily derived from activated/infected monocytes that traffic across the blood-brain barrier, rather than virus directly infecting the choroid plexus, then infecting the CSF, and finally the brain.

                  1071.     Short-Echo-Time ¹H MRS of the Mouse Lacking Prion Protein (Prnp-/-) at 14.1T

Cristina Cudalbu¹, Vladimir Mlynárik¹, Juliane Bremer², Adriano Aguzzi², Rolf Gruetter^1,3

¹Laboratory for Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; ²Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland; ³Departments of Radiology, Universities of Lausanne and Geneva, Switzerland

The prion diseases form a group of fatal neurodegenerative diseases. Animal models were created to study the role of the prion protein. The aim of our study was to use in vivo 1H MRS at 14.1T to measure the neurochemical profile in mice lacking of prion protein (Prnp-/-). We have evaluated the in vivo concentration of 18 metabolites in the hippocampus of Prnp-/- mice. The Ins increase and the trend towards a decrease in Gln detected may reflect gliosis, consistent with the histological features, whereas the reduced NAA, Gln and Glu seem to indicate a dysfunction in the neurotransmitter metabolism.

                  1072.     Novel Treatment Strategy in Mouse Model of Maple Syrup Urine Disease

William J. Zinnanti¹, Jelena Lazovic², John Flanagan³

¹Biochemistry, Pennsylvania State University, Hershey, PA, USA; ²Biology, California Institute of Technology, Pasadena, CA, USA; ³Biochemistry, Pennsulvania State University, Hershey, PA, USA

Maple syrup urine disease (MSUD) is an inborn error of branched-chain amino acid (BCAA) metabolism that requires life-long leucine restriction and monitoring. Despite strict diet adherence, children with MSUD commonly suffer encephalopathy associated with catabolic stress of non-specific childhood illnesses. Encephalopathy may involve accumulation of brain leucine and usually results in life-threatening cerebral edema and death. Using a recently developed mouse model of MSUD, we show development of brain damage after induction of encephalopathy with a high-protein diet. Administration of 5% norleucine reduces brain leucine accumulation, delays encephalopathy and enhances survival of MSUD mice.

                  1073.     Diffusion Tensor Imaging of Rat Model of Obsessive-Compulsive Disorder

Michael Dagan¹, Oded Klavir², Lior Brimberg², Daphna Joel², Yaniv Assaf¹

¹Department of Neurobiology, Tel Aviv University, Tel Aviv, Israel; ²Department of Psychology, Tel Aviv University, Tel Aviv, Israel

The localization of cognitive domains can be achieved by functional imaging modalities. It was recently shown that voxel-wise correlation between diffusion tensor imaging (DTI) indices and various behavioral measures allows brain localization of cognitive performance. In the present study we localized the behavioral manifestation of the signal attenuation (SA) rat model of obsessive-compulsive disorder (OCD) using DTI. It was found the FA and ADC reduces in many areas of the limbic system (mainly the hippocampus) as well as in the ventral striatum. These results suggest the behavior-DTI correlation may be used for characterization of plasticity induced morphological tissue changes.

                  1074.     Using MRI to Quantify Optic Nerve Injury in Monkeys with Experimental Glaucoma: Atrophy and Diffusivity Effects

Alexandre Coimbra¹, Miller Ogidigben², Robert Peiffer², Lynn O'Neil-Davis², Marie Holahan¹, Jacquelynn Cook¹, Donald Williams¹

¹Imaging, Merck Research Laboratories, West Point, PA, USA; ²Ophthalmic Research, Merck Research Laboratories, West Point, PA, USA

Glaucoma is a disease of the optic nerve (ON) whose pathophysiology is poorly understood and clinical management is currently limited to intraocular pressure reduction strategy. Current methods for examining ON degeneration in glaucoma are ex-vivo preclinical studies and in-vivo imaging of nerve fiber layer in the periphery of the ON head. The present study accesses the ability of MRI to quantify degeneration of the ON in the retroorbital space of laser-induced glaucoma monkeys and shows that MRI renders quantitative indices that correlate with atrophy and intra-ocular pressure (IOP) and may be used to study ON degeneration induced by increased IOP.

                  1075.     Histological Confirmation of the Bilateral Effect of Unilateral Nerve Injury Detected by ²H NMR

Tal Ben-David¹, Galit Saar¹, Hadassah Shinar¹, Gil Navon¹

¹School of Chemistry, Tel Aviv University, Tel Aviv, Israel

Our original finding of the surprising effect of the unilateral sciatic nerve injury on the contralateral nerve by ²H double quantum filtered NMR, is now confirmed by the histological finding. The comparison of the NMR and the histology helps us in the assignment of the satellites with the quadrupolar splittings of 200 and 500 Hz to the water of the endoneurium and the myelin respectively.

                  1076.     Long Term Effects of Recurrent Hyperglycemia on Hippocampal Neurochemistry in Developing Rats

Ivan Tkac¹, Kathleen Ennis², Raghavendra Rao²

¹Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA; ²Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

In vivo ¹H NMR spectroscopy at 9.4T was used to investigate long-term effect of the recurrent hyperglycemia on the developing brain. Hyperglycemia of graded severity was induced in rat pups from postnatal day (P)3 to P12 and the spectroscopic data were collected on P30. Changes in Asc, Glu, PE and Tau indicated long-term alternation in hippocampal neurochemical profile. These finding imply that recurrent HG may have a role in the cognitive deficits common in preterm infants.

                  1077.     MRI Reveals Brain Asymmetry Following 6-OHDA Lesions in the Mouse Brain

Stephen J. Sawiak¹, Nigel I. Wood², G B. Williams¹, A J. Morton³, T A. Carpenter¹

¹Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, UK; ²Department of Pharmacology, University of Cambridge; ³Department of Pharmacology, University of Cambridge, UK

6-OHDA (6-Hydroxydopamine) lesions are commonly used to selectively target dopaminergic neurons in the brain. This pilot study examines how MRI can be used to assess the morphological changes following lesioning, by focusing in particular on asymmetry. Images were registered to a symmetric target and SPM was used with paired t-test on the Jacobian determinants (local volume changes) between flipped and unflipped images to find lateral effects. The method detected both the lesion and asymmetric morphology in the striatum, showing it will be useful in a larger, longitudinal in vivo study.

                  1078.     S. Aureus Abscess Development in a Murine Model Measured Using MR Relaxometry and Diffusion Tensor Imaging

Michael Douglas Boska¹, Mariano Uberti¹, Amy Aldrich², Erin McIntyre¹, Tammy Kielian²

¹Radiology, University of Nebraska Medical Center, Omaha, NE, USA; ²Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA

This murine model of bacterial brain abscess has been used extensively for studying the molecular and cellular events accompanying disease progression. This work extends prior studies by using quantitative MRI to characterize lesion development. Initial results demonstrate high T₁ three days after infection in both the lesion and the surrounding tissue shown to be composed of activated macrophages/microglia. Day 7 shows the initial formation of the abscess wall as an area of low T₁ and high FA which progresses to a more organized lesion and wall, reflected as decreasing T₁, decreasing D_av, and increasing FA.

                  1079.     Evidence That Exposure to Escalating Doses of Vaporized Alcohol Causes Increase in the Concentration of Choline-Containing Compounds in the Basal Ganglia of the Rat

Dirk Mayer^1,2, Natalie M. Zahr^2,3, Juan Orduna², Edith V. Sullivan³, Adolf Pfefferbaum^2,3

¹Radiology, Stanford University, Stanford, CA, USA; ²Neuroscience Program, SRI International, Menlo Park, CA, USA; ³Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA

An MRS study using constant time point-resolved spectroscopy (CT-PRESS) of rats reported an increase in the signal from choline-containing compounds (Cho) in the basal ganglia with escalating exposure to vaporized alocohol. This signal change could be explained by either a change in concentration or in transverse relaxation constant (T₂). Here we used the CT-PRESS data to calculate the T₂s and echo-time corrected signal intensities. The results provide confirmation for the conclusion that the increase in Cho observed with increasing exposure to vaporized alcohol was due to an increase in metabolite concentration rather than a change in T₂.

                  1080.     Binge Ethanol Induced Structural and Neurochemical Changes in the Rat Brain Detectable at 3T

Natalie May Zahr^1,2, Dirk Mayer^2,3, Torsten Rohlfing², Michael Hasak², Oliver Hsu^1,2, Shara Vinco², Juan Orduna², Edith V. Sullivan¹, Adolf Pfefferbaum^1,2

¹Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA; ²Neuroscience Program, SRI International, Menlo Park, CA, USA; ³Radiology, Stanford University, Stanford, CA, USA

The effects of binge ethanol (EtOH) exposure and abstinence on the rodent brain were examined using MR imaging and spectroscopy (MRS). Intragastric EtOH administration (4d) resulted in blood alcohol levels of ~258mg/dL and brain damage detected on FSE images as an increase in lateral ventricular cerebral spinal fluid (CSF) volume. Abstinence (7d) was associated with CSF volume normalization. EtOH exposure was associated with an MRS detectable EtOH peak, a decrease in N-acetyl-aspartate and total creatine, and an increase in choline-containing compounds; metabolite levels returned to baseline with abstinence. These results suggest that binge EtOH exposure can transiently damage the brain.

                  1081.     Short-Echo-Time 1H MRS Studies of Alcohol Exposure on the Mouse Brain Over-Expressing  Glutamate Dehydrogenase

Wen-Tung Wang¹, Sang-Pil Lee², Elias Michaelis³, In-Young Choi^1,4

¹Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, USA; ²1Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, USA; ³Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, USA; ⁴Department of Neurology, Molecular & Integrative Physiology, Hoglund Brain Imaging Center, Kasnas City, KS, USA

Localized in vivo 1H magnetic resonance spectroscopy (MRS) was used to study hippocampal and striatal metabolite levels in the transgenic mice, who have mutation in glutamate dehydrogenase 1 (Glud1) and thus are hypersensitive to ethanol, as well as age-matched wild type mice. MRS data were acquired from hippocampus and striatum in the brain of both groups before and after ethanol diet. Our results show that there were small changes between the neurochemical profiles of the wt and the Glud1 tg mice, especially for metabolites Glu, Gln, and Asp linked to Glu metabolism, suggesting a modest effect of Glud over-expressing on amino acid homeostasis. With 2-week ethanol diet, the Gln level had significant changes for both brain regions in both wt and Glud tg mice. It remains to be determined whether Glud over-expressing will exacerbate the chronic effect of alcohol on the brain.

                  1082.     Diffusion Tensor Imaging Supports the Cytotoxic Origin of Brain Edema in Experimental Hepatic Encephalopathy

Laia Chavarria¹, Marc Oria¹, Juli Alonso², Juan Córdoba¹, Silvia Lope-Piedrafita³

¹Liver Unit, CIBEREHD, Hospital Vall Hebron, Barcelona, Spain; ²Magnetic Resonance Unit, CIBEREHD, Hospital Vall Hebron, Barcelona, Spain; ³Servicio de Resonancia Magnética Nuclear, CIBER-BBN, Universidad Autónoma de Barcelona, Cerdanyola del Valles, Barcelona, Spain

T2 mapping, ADC mapping and localized spectroscopy were performed on a rat model of hepatic encephalopathy aiming to detect brain abnormalities that support the development of brain edema secondary to the metabolism of ammonia to glutamine in astrocytes. An increase in ADC was detected compatible with the development of cytotoxic brain oedema. This abnormality was present at early stages, precedes the development of neurological manifestations and is accompanied by an increase in glutamine due to ammonium accumulation and a decrease in myo-inositol to compensate for it. At coma stage, a significant increase in lactate was observed, sign of anaerobic metabolism activation.

                  1083.     A Volumetric Analysis of the Adult Zebra Finch Brain After Single and Repetitive Ecstasy Exposure

Parastou Foroutan^1,2, Susanne L. T. Cappendijk³, Samuel C. Grant^1,2

¹The National High Magnetic Field Laboratory, Tallahassee, FL, USA; ²Chemical & Biomedical Engineering, Florida State University, Tallahassee, FL, USA; ³Biomedical Sciences, College of Medicine, The Florida State University, Tallahassee, FL, USA

Ecstasy use has increased worldwide in recent years, and previous human studies have shown that users may experience lasting impairment in learning and cognition. In this study, Ecstasy-induced neurodegeneration was examined in the zebra finch, a model for studies of cognitive processes and neuronal plasticity. To assess changes in excised finch brain, high-resolution MRI at 11.75 T combined with histology was performed. Numerous structures in the finch brain could be segmented without exogenous contrast enhancement. Although volumetrics showed no statistical difference in the adult finch in response to acute Ecstasy exposure, demyelination of certain areas may have been identified.

                  1084.     Effect of Long-Term Caffeine Consumption on Glucose Transport and Osmolarity Alterations in the Hippocampus of STZ-Induced and Goto-Kakizaki Diabetic Rats: in Vivo¹H MRS Study at 9.4 T

João M. N.  Duarte^1,2, Rui A. Carvalho², Rodrigo A. Cunha², Rolf Gruetter^1,3

¹LIFMET - CIBM, EPFL, Lausanne, Vaud, Switzerland; ²Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; ³Departments of Radiology, Universities of Lausanne and Geneva, Switzerland

Diabetes may affect the morphology and plasticity of the hippocampus, leading to cognitive impairment. We now studied alterations of metabolism in the hippocampus of diabetic rats and the protective effect of caffeine consumption.

                  1085.     An Investigation Into Young and Aged Rat Brain Volume Differences by Optimized Voxel-Based Morphometry

Ronan Kelly¹, Laurence O' Dwyer¹, Eric O' Hanlon¹, Colm Connolly¹, Marina Lynch², Christian Kerskens¹

¹Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland; ²Department of Physiology, Trinity College Dublin, Dublin, Ireland

Voxel-based morphometry has proven to be a reliable tool in analysing between group volume concentration differences in the human brain. Here we describe a modulated application of this tool, that of studying volume changes in the rat brain. Skull-stripped MRI images were registered to a generic brain template image, the output of which was averaged to produce a study-specific template file. A variety of statistical tests was then carried out, thus creating statistical maps highlighting regions of significant decline with age. Among these regions were the primary and secondary visual cortices, and CA1 and CA2 fields of the hippocampus.

                  1086.     SPMMouse: A New Toolbox for SPM in the Animal Brain

Stephen J. Sawiak¹, Nigel I. Wood², G B. Williams¹, A J. Morton², T A. Carpenter¹

¹Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, UK; ²Department of Pharmacology, University of Cambridge, UK

SPM is a popular package for structual and functional morphometry though it is not easy to use for non-human brains. We present SPMMouse - a toolbox allowing SPM to use any non-human brain for morphometry, including a demonstration of its use for the mouse brain. The tool allows SPM 'glass brains' to be created from any image, and automatically adjusts defaults length scales based on the headers of image files or user entered data. Priors for image registration and template prior probability maps are included for the C57 mouse brain. This open-source software will be available from the authors.