MRS: Cancer & Aberrant Metabolism

Tuesday 23 April 2013

Sandeep Ganji¹, Keith M. Hulsey¹, Elizabeth A. Maher^2,3, and Changho Choi^4
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.

Christine Leon^1,2, 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. Larson^1
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.

Stefan H. Hoffmann¹, Alexander Radbruch^1,2, Wolfhard Semmler¹, and Armin M. Nagel^1
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.

Lenka Minarikova¹, Stephan Gruber¹, Wolfgang Bogner^1,2, Katja Pinker-Domenig³, Siegfried Trattnig¹, Thomas Helbich³, and Marek Chmelik^1
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).

Hailiang Huang¹, Emily Decelle¹, Yannick Berker¹, Andreas Schuler^1,2, Isabel Dittman^1,2, Li Su³, Eugene J. Mark¹, Mark J. Daly¹, David C. Christiani^1,3, and Leo L. Cheng^1
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.

Fei Du¹, Alissa Cooper², Thida Thida², Selma Sehovic², Scott Lukas¹, Bruce Cohen¹, Xiaoliang Zhang³, and Dost Ongur^1
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.

Bretta Russell-Schulz¹, Alex L. MacKay^1,2, and Blair R. Leavitt^3
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.

Ivan I. Kirov¹, Assaf Tal¹, James S. Babb¹, Joseph Herbert², and Oded Gonen^1
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 cm^3 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).

Kim C.C. van de Ven^1,2, Marinette van der Graaf^1,3, Bastiaan E. de Galan⁴, Cees J. Tack⁴, and Arend Heerschap^1
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.

Naranamangalam R. Jagannathan¹, Uma R. Sharma¹, Sujeet R. Mewar¹, and Govind K. Makharia^2
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.