Joint Annual Meeting ISMRM-ESMRMB 2014 10-16 May 2014 Milan, Italy

Molecular Imaging & Spectroscopy

Wednesday 14 May 2014   10:00 - 11:00

Space 1/Power Poster Theatre & Traditional Poster Hall 
Moderators: Jerry D. Glickson Ph.D., Michal Neeman, Ph.D.

Design of Novel Synthetic Antiferromagnets for Nano-RF reporters for Single Cell Tracking
Karl F. Stupic1, Kathryn E. Keenan1, Edward V. Denison1, Charles A. E. Little1, and Stephen E. Russek1
1National Institute of Stanards and Technology, Boulder, Colorado, United States

A new class of nanofabricated contrast agents, which operate as nano-resonators, is proposed and modeled. The agents are based on nanoscale synthetic antiferromagnets (nano-SAFs) which have resonant modes that are engineered to have large spectral densities at MRI proton frequencies. The resonance frequencies can be adjusted by tuning the layer thicknesses to give the desired resonances at all clinical field strengths. Initial nano-SAFs, with 830 nm diameter and 70 nm thicknesses, have been fabricated and imaged at 1.5 T. Strong T1 contrast was not observed indicating that smaller dimensions are required.


  0472.   Exploring the inherent CEST MRI signal of anticancer drug gemcitabine
Yuguo Li1,2, Kannie Chan1,2, peter van Zijl1,2, Bert Vogelstein3, Michael McMahon1,2, Shibin Zhou3, and Guanshu Liu1,2
1Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2FM Kirby center, Kennedy Krieger Institute, Baltimore, MD, United States, 3Ludwig Center, Howard Hughes Medical Institute and Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Non-invasive tracking of drug delivery is of great clinical interest. Herein, we explored a direct way to track liposome mediated delivery of gemcitabine, a first-line drug for treating pancreatic cancer. We show that this can be achieved using its inherent Chemical Exchange Saturation Transfer (CEST) MRI signal at 2.1 and 1.0 ppm originating from the exchangeable amino and hydroxyl protons, respectively. Unlike traditional approaches, the CEST MRI detection doesn’t require the use of extra contrast agents, and is able to directly convert the gemcitabine-loaded nanoparticle drug delivery system into a theranostic system.


  0473.   Generation of Multicolor/multiparametric MRI-CEST maps of murine tumor by using YbHPDO3A and Dy-loaded Red Blood Cells.
Giuseppe Ferrauto1, Enza Di Gregorio1, Daniela Delli Castelli1, Enzo Terreno1, and Silvio Aime1
1Molecular Biotechnologies & Health Sciences, Molecular Imaging Center, Torino, Italy

Three key hallmarks of the tumor development are represented by the increased vascular volume, the enhanced vascular permeability and the acidification of the extracellular/extravascular pH (pHe). CEST contrast agents appear well suitable to visualize simultaneously the three biomarkers by using the currently available 1H-MRI scanners. YbHPDO3A, a small hydrophilic, well tolerated paraCEST agent, chemical analogue of the clinically approved ProHance, provides the way to get information both on change in pHe and on change in vascular permeability. Semi-quantitative information on the vascular volume have been obtained by using Dysprosium- loaded Red Blood Cells, a new kind of CEST contrast agent.


  0474.   First clinical experience using fluorine-19 MRI to track immunotherapeutic dendritic cells in colorectal cancer patients
Eric T Ahrens1, Anthony Balducci2, Brooke Helfer2, Amy Wesa2, Charles O'Hanlon2, Claudiu Schirda3, David Bartlett4, and Pawel Kalinski4
1Radiology, University of California at San Diego, La Jolla, CA, United States, 2Celsense, Inc., Pittsburgh, PA, United States, 3Radiology, University of Pittsburgh, Pittsburgh, PA, United States, 4Surgical Oncology, University of Pittsburgh, Pittsburgh, PA, United States

Cell therapies, such as those employing immune or stem cells, can benefit from non-invasive imaging to visualize cells following transfer into the patient. We described the first clinical use of a fluorine-19 MRI tracer agent designed for MRI cell tracking. We labeled autologous immunotherapeutic dendritic cells (DCs) with a perfluorocarbon (PFC) tracer agent ex vivo. Labeled DCs were inoculated into colorectal cancer patients. Cells were detected using a 3T scanner using 19F MRI/MRS. Clinical 19F-based cell tracking is feasible and provides unambiguous information about the cell location, with no background signal, and can be used to quantify cells in situ.


Natural abundance in vivo 17O measurements at 9.4T
Klaus Möllenhoff1, Jörg Felder1, Sandro Romanzetti1, Ali Gordji-Nejad1, and N Jon Shah1,2
1INM-4, Research Centre Jülich GmbH, Jülich, Germany, 2Department of Neurology, RWTH Aachen University, Aachen, Germany

Knowledge of quantitative values of CMRO2 is of great interest to follow the treatment of the diseases. In the last decades, 15O was used to quantify CMRO2 with the use of PET imaging as a gold standard. In this preliminary study we show the feasibility of in vivo 17O imaging experiments with a sufficient SNR in acceptable measurement times at 9.4T in humans.


  0476.   Hyperpolarized [1-13C] glutamate: a surrogate marker of IDH1 mutational status in glioblastoma
Myriam M Chaumeil1, Peder E.Z. Larson1, Sarah M Woods1, Pia Eriksson1, Larry Cai1, Aaron Robinson2, Daniel B Vigneron1, Sarah J Nelson1, Russell O Pieper2, Joanna J Phillips2, and Sabrina M Ronen1,2
1Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States, 2Brain Tumor Research Center, UCSF, San Francisco, CA, United States

Following injection of hyperpolarized α-ketoglutarate, we previously reported the detection of hyperpolarized 2-hydroxyglutarate formation in IDH1-mutant tumors, not in in IDH1 wild-type, using 2D 13C dynamic CSI at clinical field strength. Here, we show that, contrarily to 2-hydroxyglutarate, hyperpolarized glutamate formation from hyperpolarized α-ketoglutarate could be detected in IDH1 wild-type perfused cells and tumors only, not in cells or tumors harboring the IDH1 mutation. Biochemical assays were performed to assess the underlying mechanisms. Hyperpolarized glutamate could thus potentially serve as a non-invasive additional surrogate marker of IDH1 mutational status in brain tumors.


  0477.   Detection of transgene expression using hyperpolarized 13C urea and diffusion-weighted MRS - permission withheld
P. Stephen Patrick1, Mikko I. Kettunen1,2, Sui-Seng Tee1, Tiago B. Rodrigues1, Eva M. Serrao1, Kerstin Timm1, and Kevin M. Brindle1
1CRUK Cambridge Institute and Department of Biochemistry, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom, 2A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland

Diffusion spectroscopy of hyperpolarized [13C]urea was used to assess urea transporter expression as a potential gene reporter in vivo. Significantly decreased apparent diffusion coefficient was measured for urea transporter expressing tumors compared to their non-expressing controls. No differences in tumor cellularity were observed. The results suggest that expression of transporter in combination with diffusion spectroscopy might be used as another approach for detecting gene reporter expression.


  0478.   Regional variations of GABA, glutamate, glutamine and NAAG in the human brain, as measured by 1H MRS at 7T in vivo
Changho Choi1, Sandeep Ganji1, Zhongxu An1, and Akshay Madan1
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas, United States

We report regional variations in metabolite levels in healthy human brain, focusing on GABA, glutamate, glutamine, and N-acetyl-aspartyl-glutamate. A GABA-tailored PRESS sequence (TE = 92 ms) was used, at 7T, to measure the metabolites in gray matter (GM) and white matter (WM) dominant regions in the frontal and occipital brain in 9 healthy volunteers. Metabolite levels in pure GM and WM were obtained with linear regression of metabolite estimates vs. fractional GM contents. The result indicated that the concentrations of many metabolites are significantly different between frontal and occipital brain as well as between GM and WM.


  0479.   3D GABA imaging with high spatial resolution at 3T using a navigated MEGA-LASER MRSI sequence
Wolfgang Bogner1, Borjan Gagoski2, Aaron T Hess3, Bernhard Strasser1, Himanshu Bhat4, Dylan Tisdall5, Andre J.W. van der Kouwe5, Ellen Grant2, Siegfried Trattnig1, Bruce Rosen5, and Ovidiu C Andronesi5
1High-field MR Center, Department of Biomedical Imaging and Image-guided Therapy, Medical University Vienna, Vienna, Vienna, Austria, 2Fetal-Neonatal Neuroimaging & Developmental Science Center, Boston Children's Hospital, Harvard Medical School, Boston, United States, 3Department of Cardiovascular Medicine, John Radcliffe Hospital, University of Oxford Centre for Clinical Magnetic Resonance Research, Oxford, United Kingdom,4Siemens Healthcare, Charlestown, United States, 5Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, United States

GABA, the major inhibitory neurotransmitters, is difficult to detect. Single-voxel MEscher-GArwood (MEGA) PRESS editing MRS is the most popular technique for non-invasive detection of GABA, but it has several limitations: MEGA editing is a subtraction technique and, therefore, prone to scanner instabilities and motion artifacts. Chemical shift displacement errors (CSDE) in PRESS reduce editing efficiency. Single-voxel localization does not allow the characterization of spatial concentration differences. Therefore, our study introduces a robust MEGA-editing 3D-CSI sequence for 3T that uses LASER localization to eliminate CSDE; spiral encoding to accelerate acquisition; and real-time motion-/B0-correction with selective data reacquisition to eliminate subtraction artifacts.


  0480.   Preliminary Study of Cerebral NAD Metabolism and Redox State in Parkinson’s Patients - permission withheld
Xiao-Hong Zhu1, Byeong-Yeul Lee1, Susan Rolandelli2, Ming Lu1, Paul Tuite2, and Wei Chen1
1CMRR, Department of Radiology, University of Minnesota Medical School, Minneapolis, MN, United States, 2Department of Neurology, University of Minnesota Medical School, MN, United States

Energy failure from mitochondrial dysfunction has been proposed as a central mechanism leading to neuronal death in a range of neurodegenerative diseases. However, it is difficult to evaluate the link between abnormal energetics and impaired mitochondrial functions associated with neurodegeneration in living human brain. Recently a new high-field in vivo 31P MRS approach has been developed and its capability for non-invasively assessing the intracellular nicotinamide adenine dinucleotide (NAD) contents and its redox ratio has been demonstrated in healthy human brain at 7T. In the present study, we applied this newly developed method for quantitative assessment and comparison of NAD redox state in Parkinson’s disease (PD) patients and matched controls. The preliminary findings demonstrated abnormal cerebral energy metabolism associated with PD and the potential influences of gender in the disease.


5D Echo-planar J-resolved spectroscopic imaging of cerebral metabolites in HIV-infected youth: a preliminary study
Neil E. Wilson1, Zohaib Iqbal1, Brian L. Burns1, Margaret A. Keller1, and M. Albert Thomas1
1University of California, Los Angeles, CA, United States

Perinatally HIV-infected youths often have compromised neurocognitive function that may be correlated with abnormal cerebral metabolite concentrations. Here, we look at 2D J-resolved spectra in a 3D acquisition acquired using an 8x undersampling and look for regional differences in metabolite concentrations between healthy and HIV-infected children. Two different reconstruction methods are compared.


  0482.   1H-MRS study in investigating the effect of dioscorea modified pill to the cognitive impairment of patients with VCIND
Jun Chen1, Jinhuan Liu1, Zihu Tan2, Qiong Yang2, Hanchao Lan2, Yilin Zhao1, Dongjie Huang1, Qizhong Xu1, and Liang Zhang1
1Department of Radiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China, 2Department of Geriatrics, Hubei Hospital of Traditional Chinese Medicine, Wuhan, Hubei Province, China

Vascular Cognitive Impairment No Dementia (VCIND) is introduced to identify the earliest stage of cognitive decline associated with vascular disease, which does not meet dementia criteria but with an increased risk of death and institutionalization1. Early detection of VCIND has significant clinical implications for a valid prognosis and treatement2. Proton magnetic resonance spectroscopy (1H-MRS) has been proved useful in investigating neurodegenerative diseases3. In this study, the therapeutic effect of Dioscorea modified pill and Aricept to VCIND patients was evaluated using brain 1H-MRS, mini-mental state examination (MMSE), clinical dementia rating (CDR) and Montreal Cognitive Assessment (MoCA) simultaneously and the relationship of these measurements was investigated as well.


  0483.   Effects of APOE-lower case Greek epsilon4, Age and HIV on Glial Metabolite and Cognitive Deficits
Linda Chang1, Caroline S. Jiang1, Eric Cunningham1, Steven Buchthal1, Vanessa Douet1, Marilou Andres2, and Thomas Ernst1
1Department of Medicine, University of Hawaii at Manoa, John A. Burns School of Medicine, Honolulu, Hawaii, United States, 2University of Hawaii at Manoa, Pacific Biosciences Research Center, Honolulu, Hawaii, United States

Despite effective antiretroviral medications, milder forms of HIV-associated neurocognitive disorders (HAND) remain prevalent. The apolipoprotein-E(APOE)-lower case Greek epsilon4 gene was inconsistently found to increase the risk for HAND. Whether HIV subjects with APOE)-lower case Greek epsilon4 allele(s) would show greater neuroinflammation, which may contribute to cognitive deficits, is unknown and was evaluated. 177 participants (97 seronegative controls and 80 HIV subjects) were evaluated with 1H MRS, cognitive assessments and genotyping for APOE. HIV subjects showed elevated levels of myoinositol regardless of APOE-lower case Greek epsilon4 genotype and across the agespan, which was associated with poorer cognitive function. APOE-lower case Greek epsilon4 combined with 1H MRS may be useful markers to predict HAND.


  0484.   Detection of Metabolite Changes in Response to a Varying Visual Stimulation Paradigm Using Short TE 1H MRS at 7T
Ralf Mekle1, Simone Kuehn2, Harald Pfeiffer1, Florian Schubert1, and Bernd Ittermann1
1Medical Physics, Physikalisch-Technische Bundesanstalt, Berlin, Germany, 2Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany

The goal of this study was to detect differences in steady-state metabolite levels in response to a varying stimulation paradigm in the right human visual cortex using short TE 1H MRS methodology at 7T. Instead of a strict on/off paradigm, where global physiologic effects might adversely influence MRS data acquisition, a modified stimulation condition not affecting the target voxel was employed as baseline. Nineteen metabolites were reliably quantified. A reduction of the neurotransmitter GABA and an increase of lactate were observed as the only significant effects. Differences with previous studies were attributed to the modified experimental conditions.


In vivo measurements of acute pain induced changes of GABA+ and Glx in the brain by using functional 1H-MEGA-PRESS MR spectroscopy
Marianne Cleve1, Alexander Gussew1, and Jürgen R. Reichenbach1
1Medical Physics Group, Institute of Diagnostic and Interventional Radiology I, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany

: This study comprises results of time resolved measurements of acute heat pain induced changes in excitatory (Glx) and inhibitory (GABA+) neurotransmitter turnover in the aCC by using 1H-MEGA-PRESS spectroscopy. Compared to the reference condition Glx/tCr increased significantly up to a median value of 14.2% in aCC during stimulation. At the same time, GABA+/tCr decreased by a median value of 25.4%. The Glx/tCr increase may be ascribed to the elevated glutamatergic turnover, while the GABA+/tCr decrease may reflect reduced activity of the inhibitory system during pain processing.