ISMRM 21st Annual Meeting & Exhibition 20-26 April 2013 Salt Lake City, Utah, USA

MRS: Cancer & Aberrant Metabolism
Tuesday 23 April 2013
Room 255 BC  10:00 - 12:00 Moderators: Zaver M. Bhujwalla, Michal Neeman

10:00 0214.   
in vivo Spectroscopic Imaging of 2-Hydroxyglutarate in Human Gliomas at 7.0 T
Sandeep Ganji1, Keith M. Hulsey1, Elizabeth A. Maher2,3, and Changho Choi4
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas, United States, 2Harold C. Simmons Cancer Center, UT Southwestern Medical Center, Dallas, Texas, United States, 3Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, United States, 4Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States

We report the first in vivo spectroscopic imaging of 2HG at 7T using an optimized echo-time PRESS-based localization method in subjects with brain tumors. We present phantom and in vivo data and show the elevated 2HG levels in tumor patients. Metabolites concentration maps are also presented.

10:12 0215.   
Imaging Real-Time Cancer Metabolism with MAD-STEAM HP 13C MRSI
Christine Leon1,2, Adam B. Kerr3, Robert A. Bok4, Mark Van Criekinge1, Galen D. Reed1, Klaus Kruttwig5, Andrei Goga5, John Kurhanewicz1, John M. Pauly3, Daniel B. Vigneron1, and Peder E.Z. Larson1
1Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, 2UC Berkeley-UCSF Graduate Program in Bioengineering, Berkeley and San Francisco, CA, United States, 3Magnetic Resonance Systems Research Laboratory, Department of Electrical Engineering, Stanford University, Stanford, CA, United States, 4Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, 5Department of Medicine, University of California, San Francisco, San Francisco, CA, United States

Using MAD-STEAM single-voxel acquisition and reconstruction, real-time conversion can be directly observed, which may provide increased specificity for monitoring intracellular enzyme activity. Extending the method to dynamic MAD-STEAM MRSI provides improved localization of those changes, which can better differentiate tumor versus normal. In transgenic models of cancer, real-time generation of lactate was observed in a tumor and increased conversion to alanine was observed during tumor formation. This new technique has great biomedical potential as it could be used to better measure and understand tumor metabolic changes with cancer progression and response to therapy.

10:24 0216.   
Partial Volume Corrected CMRO2 Determination in a Glioblastoma Patient by 17O MRI
Stefan H. Hoffmann1, Alexander Radbruch1,2, Wolfhard Semmler1, and Armin M. Nagel1
1Dpt. of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, 2Department of Neuroradiology, University of Heidelberg, Heidelberg, Germany

In tumor cells energy production is shifted from aerobic to anaerobic metabolization of glucose and reduced CMRO2 was found in brain tumors in 15O PET studies. We present an 17O2 inhalation experiment performed in a glioblastoma patient. Direct 17O MRI was carried out to quantify CMRO2 in brain tissue and in the tumor region. Partial volume correction was applied to the dynamic data before CMRO2 determination. The data showed reduced CMRO2 in the tumor center and perifocal edema compared to brain tissue. The CMRO2 values we obtained by 17O MRI agree well with previous PET results.

10:36 0217.   
Improved Quantification of Choline in Breast MRS Using Dixon Imaging Water Referencing
Lenka Minarikova1, Stephan Gruber1, Wolfgang Bogner1,2, Katja Pinker-Domenig3, Siegfried Trattnig1, Thomas Helbich3, and Marek Chmelik1
1MR Center of Excellence, Department of Radiology, Medical University of Vienna, Vienna, Vienna, Austria, 2Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States, 3Division of Molecular and Gender Imaging, Department of Radiology, Medical University of Vienna, Vienna, Vienna, Austria

We propose semi-quantitative total choline signal estimation in 3D MR spectroscopic imaging at 3 T in breasts with additional correction to water content for each voxel, using information extracted from Dixon imaging to correct SNR of tCho. Our water-referencing correction improves tCho signal amplitudes homogeneity throughout a phantom volume therefore; corrected signal values reflect more real tCho concentrations. Furthermore, spatial CSI matrix shift can considerably influence tCho SNR in patient’s data. Our method is able to compensate for deviations in matrix positioning, which can noticeably help in repeated measurements (e.g. therapy monitoring).

10:48 0218.   
Using Paired Tissue and Serum Samples to Characterize Human Lung Cancer Metabolomics with ex vivo 1H HRMAS MRS
Hailiang Huang1, Emily Decelle1, Yannick Berker1, Andreas Schuler1,2, Isabel Dittman1,2, Li Su3, Eugene J. Mark1, Mark J. Daly1, David C. Christiani1,3, and Leo L. Cheng1
1Massachusetts General Hospital, Boston, Massachusetts, United States, 2Charité Universitätsmedizin, Berlin, Germany, 3Harvard School of Public Health, Boston, Massachusetts, United States

Despite lung cancer being the primary cause of cancer related death in both men and women in the United States, there is no early screening tool available to the general public. Due to the high costs and the radiation exposure of CT or PET, these technologies are not feasible as screening tools. Clinicians desperately need a new diagnostic tool to provide biochemical information that is essential for making early diagnoses and subsequent treatment decisions. In this study we are assessing the matched tissue and sera metabolomic profiles of lung cancer patients to discover serum metabolic markers for lung cancer.

11:00 0219.   in vivo Evidence for Abnormal Cerebral Bioenergetics in Schizophrenia Measured by 31P Magnetization Transfer Spectroscopy
Fei Du1, Alissa Cooper2, Thida Thida2, Selma Sehovic2, Scott Lukas1, Bruce Cohen1, Xiaoliang Zhang3, and Dost Ongur1
1McLean Hospital, Harvard Medical School, Belmont, MA, United States, 2McLean Hospital, Belmont, MA, United States, 3Department of Radiology, University of California, San Francisco, San Francisco, CA, United States

Schizophrenia (SZ) is a common and severe brain disorder associated with poor functional outcome. Despite suggestions of abnormal mitochondrial and bioenergetic function in SZ, creatine kinase (CK) reaction rate, a direct biomarker of bioenergetics, has not previously been measured in vivo. Here, we report our primary results using a novel 31P MRS approach; the CK reaction rate was found a substantial reduction in SZ. Therefore we provided first direct and compelling in vivo evidence for a specific bioenergetic abnormality in SZ, which would provide crucial information for understanding underlying molecular mechanism, and novel targets for drug development in SZ.

11:12 0220.   
Longitudinal Magnetic Resonance Spectroscopy in Premanifest and Early Huntington Disease.
Bretta Russell-Schulz1, Alex L. MacKay1,2, and Blair R. Leavitt3
1Radiology, University of British Columbia, Vancouver, BC, Canada, 2Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada, 3Medical Genetics, University of British Columbia, Vancouver, BC, Canada

Huntington disease (HD) is a neurodegenerative disease that has no cure and leads to severe impairment, both cognitive and physical. This study is an extension of the earlier Track-HD study, examining MRS metabolites longitudinally in premanifest and early HD compared to controls across three years, in search of biomarkers for disease manifest and progression. The most significant changes in metabolite concentrations between groups were seen in tNAA, tCr and mI. tNAA and tCr showed the same pattern between the subject groups at all 4 timepoints. mI is a possible biomarker not only for disease identification but also disease progression.

11:24 0221.   
Serial Proton MR Spectroscopy of Gray and White Matter in Relapsing-Remitting Multiple Sclerosis
Ivan I. Kirov1, Assaf Tal1, James S. Babb1, Joseph Herbert2, and Oded Gonen1
1Radiology, New York University, New York, NY, United States, 2Neurology, New York University, New York, NY, United States

Proton magnetic resonance spectroscopic imaging (1H-MRSI) was used to characterize and follow global gray and white matter (GM/WM) metabolism in 18 early relapsing-remitting multiple sclerosis patients with semi-annual scans over 3 years. Absolute concentrations of N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (mI) were obtained for all GM and WM in the 360 cm3 1H-MRSI volume-of-interest. Patients’ average WM Cr, Cho and mI concentrations (over all time points) were 8%, 12% and 11% higher than controls’ (p≤0.01), while their WM NAA was 6% lower (p=0.07). There were increases with time of patients’ WM Cr, Cho and NAA (all p‹0.05).

11:36 0222.   Cerebral Glucose Metabolism During Euglycemia and Hypoglycemia in Patients with Type 1 Diabetes
Kim C.C. van de Ven1,2, Marinette van der Graaf1,3, Bastiaan E. de Galan4, Cees J. Tack4, and Arend Heerschap1
1Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, 2Present Address: Philips Healthcare, Best, Netherlands, 3Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, 4General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

Cerebral glucose metabolism was studied by 13C-MRS during [1-13C]glucose infusion under euglycemic and hypoglycemic conditions in patients with uncomplicated type 1 diabetes mellitus (T1DM). Time courses of 13C-label incorporation into different metabolites were used to calculate the tricarboxylic acid cycle flux (VTCA) by a one-compartment metabolic model. VTCA did not differ between the two glycemic conditions. However, upon comparison with results previously obtained among healthy volunteers, VTCA was approximately 45% higher in patients than in healthy subjects under hypoglycemic conditions. This finding suggests that the brain of T1DM patients may endure moderate hypoglycemia better than that of healthy subjects.

11:48 0223.   Metabonomics of Gastrointestinal Mucosa in Celiac Disease Using In-Vitro Proton NMR Spectroscopy
Naranamangalam R. Jagannathan1, Uma R. Sharma1, Sujeet R. Mewar1, and Govind K. Makharia2
1Department of NMR & MRI Facility, All India Institute of Medical Sciences, New Delhi, Delhi, India, 2Department of Gastroenterology & Human Nutrition, All India Institute of Medical Sciences, New Delhi, Delhi, India

Celiac disease is chronic autoimmune disorder caused by ingestion of dietary protein gluten present in wheat, barley and rye in genetically susceptible individuals. In vitro proton NMR spectroscopy of intestinal mucosal biopsies of patients with celiac disease showed higher concentration of leucine, aspartate, succinate and fumarate compared to controls. Accumulation of aspartate in intestinal mucosa may lead to deficiency of aspartate for urea cycle in liver and may be the reason for liver abnormalities in celiac disease patients. Accumulation of succinate suggests abnormality in Kreb’s cycle leading to energy deficiency and might affect processes of maintenance of mucosal integrity.