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

Non-Proton MRS

Wednesday 14 May 2014
Blue 1 & 2  10:00 - 12:00 Moderators: Naranamangalam R. Jagannathan, Ph.D., Linda Moy, M.D.

10:00 0532.   The Potential Advantage of High Resolution In Vivo 31P-MRS in the Assessment of Nonalcoholic Fatty Liver Disease - permission withheld
Yunjung Lee1 and Hyeonjin Kim1,2
1Radiology, Seoul National University Hospital, Seoul, Korea, 2Biomedical Sciences, Seoul National University, Seoul, Korea

The advantage of high resolution in-vivo 31P-MRS in assessing nonalcoholic fatty liver disease (NAFLD) was investigated at 9.4T in CCl4-treated rats. In all spectra phosphomonoester (PME) and phosphodiester (PDE) were well resolved into phosphoethanolamine (PE) and phosphocholine (PC), and into glycerophosphorylethanolamine (GPE) and glycerophosphorylcholine (GPC), respectively. Those MRS measures quantifiable only in highly resolved spectra had higher correlations with histology than those conventional MRS measures. In multivariate analyses the statistical model allowed the classification and prediction of the animals according to disease severity with 70-80% accuracy. High resolution in-vivo 31P-MRS may further extend the applicability of 31P-MRS in assessing NAFLD.

10:12 0533.   Glutamine is the main source of 2-HG production in IDH1 mutant glioma cells
Jose Luis Izquierdo Garcia1, Pia Eriksson1, Cai Larry1, Myriam Chaumeil1, Russell O Pieper2, Joanna J Phillips2, and Sabrina M Ronen1
1Radiology, UCSF, San Francisco, CA, United States, 2Neurological Surgery, Helen Diller Research Center, UCSF, San Francisco, CA, United States

Mutations in Isocitrate dehydrogenase (IDH1) have been reported in over 70% of low-grade gliomas and secondary glioblastomas (GBM) and they are associated with the accumulation of the oncometabolite 2-HG within the tumor. Despite these observations, the metabolic fluxes associated with 2-HG production are not fully understood. This study demonstrates using 13C MRS in combination 13C-labeled glucose and glutamine that glucose does not contribute significantly to 2-HG production and that glutamine is the main source of 2-HG in our U87 GBM mutant IDH1 cells.

10:24 0534.   
Brain high-energy phosphates and creatine kinase synthesis rate under graded isoflurane anesthesia: An in vivo 31P Magnetization Transfer Study at 11.7 Tesla
Andrew Bresnen1 and Timothy Q. Duong1
1UTHSCSA - Research Imaging Institute, San Antonio, Tx, United States

The accelerated 31P Four Angle Saturation Transfer (FAST) technique was implemented to evaluate the brain high-energy phosphates and the forward CK synthesis rate under graded isoflurane anesthesia. High field (11.7 Tesla) and a small sensitive surface coil were used to improve 31P signal sensitivity. The major findings were: i) the forward creatine kinase rate and the metabolic flux of the rat brain were reliably measured, and ii) changing isoflurane concentration from 1.2% to 2.0% did not change the PCr and ATP concentrations, but significantly decreased the forward creatine kinase synthesis rate and the metabolic flux.

10:36 0535.   
In vivo 13C MRS in the mouse brain at 14.1 T and metabolic flux quantification during infusion of [1,6-13C2] Glucose
Marta Lai1, Bernard Lanz1,2, Carola Jaquelina del Carmen Romero1,3, Cristina Cudalbu3, and Rolf Gruetter1,4
1Laboratory of Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 2Department of Radiology, University of Lausanne, Lausanne, Switzerland, 3Centre d’Imagerie Biomedicale, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 4Departments of Radiology, University of Lausanne and Geneva, Switzerland

13C MRS in conjunction with [1,6-13C] Glucose infusion is a powerful tool to access in vivo brain energy metabolism and neurotransmission. Unfortunately, due to the intrinsic low sensitivity of 13C detection, acquisitions are commonly limited to fairly big volumes restricting its in vivo application in the rat brain. With our present work we want to overcome these limitations proving the feasibility of 13C MRS in the mouse brain at 14.1 Tesla. Successful completion of 10-minutes spectra acquisition in the mouse brain allows metabolic fluxes quantification and opens the possibility to study a wide range of transgenic mice models in vivo.

10:48 0536.   Beta Oxidation of Octanoate by Diverse Human Primary and Metastatic Brain Malignancies in an Orthotopic Transplant Model
Kumar Pichumani1, Tomoyuki Mashimo2, Koji Sagiyama1, Masaya Takahashi1, Vamsidhara Vemireddy2, Shyam Sirasanagandla2, Suraj Nannepaga2, Kimmo Hatanpaa3, Bruce Mickey4, Elizabeth Maher2, Ralph DeBeraridinis5, Craig Malloy1, and Robert Bachoo2
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States, 2Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX, United States, 3Pathology, UT Southwestern Medical Center, Dallas, TX, United States, 4Neurological Surgery, UT Southwestern Medical Center, Dallas, TX, United States, 5Children's Medical Center Research Institute, UT Southwestern Medical Center, Dallas, TX, United States

Beta oxidation of octanoate by human brain tumors in an orthotopic mouse model using 13C NMR spectroscopy

11:00 0537.   
Quantitative Assessment of Glucose Metabolism in Rat Brains using In Vivo Deuterium Magnetic Resonance
Ming Lu1, Xiao-Hong Zhu1, Yi Zhang1, Gheorghe Mateescu2,3, and Wei Chen1
1Center for Magnetic Resonance Research, University of Minnesota Medical School, Minneapolis, Minnesota, United States, 2Case Center for Imaging Research and Radiology Department, Case Western Reserve University, Cleveland, Ohio, United States, 3Chemistry, Case Western Reserve University, Cleveland, Ohio, United States

Simultaneous assessment of cerebral glucose consumption rate and associated major metabolic fluxes, such as TCA cycle, lower case Greek alpha-ketoglutarate/glutamate exchange and oxygen consumption, is crucial to understanding neuroenergetics under various physiological and pathological conditions. However, such simultaneous measurement has not been possible. In this study, a novel Deuterium MR (DMR) approach is proposed and tested in rat brains at 16.4 T. Following a brief injection of deuterated glucose, the dynamic glucose, glutamate/glutamine (Glx) and water concentration changes in the brain tissue were monitored by tracking their separate resonance signals in the 2H spectra. To test the sensitivity of this method in response to altering metabolic rates, dynamics of brain deuterated glucose and Glx under 2% isoflurane anesthesia and constant morphine infusion were compared. As expected, increasing glucose consumption and labeled Glx turnover rates were found in the morphine group. The overall results indicate that the new in vivo DMR approach is robust and reliable for simultaneously detecting the changes in glucose and Glx contents in the rat brain with superior sensitivity. When combined with metabolic modeling, simultaneous measurement of glucose consumption rate, TCA cycle flux and lower case Greek alpha-ketoglutarate/glutamate exchange rate can be achieved in animal and human brains.

11:12 0538.   Fat Compostion Determination via Combined 13C and 1H MRS at Ultra High Field
Sergey Cheshkov1,2, Ivan Dimitrov1,3, Karlos Moreno1, and Craig Malloy1,2
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States, 2Radiology, University of Texas Southwestern Medical Center, Dallas, TX, United States, 3Philips Medical Systems, Cleaveland, OH, United States

Studies indicate that composition of body adipose tissue, which is sensitive to diet, may predispose to cancer. Utilizing the increased chemical shift dispersion, proton MRS at 7T has been used as a non-invasive tool for fat composition determination in human calf muscle and breast. Compared to proton MRS, 13C with its large chemical shifts provides significant advantage in measuring multiple additional lipid fractions. In this work we investigate a combined 13C and 1H MRS benefiting from the high specificity of 13C and high signal to noise of 1H spectrum for ultimately more reliable lipid composition determination.

11:24 0539.   
Metabolic flux analysis of acetylcarnitine turnover and mitochondrial oxidation of [2-13C]acetate in rat skeletal muscle in vivo measured by 13C MRS
Jessica A.M. Bastiaansen1, Joao M.N. Duarte1, and Rolf Gruetter1,2
1Laboratory of Functional and Metabolic Imaging, EPFL, Lausanne, Switzerland, 2Department of Radiology, University of Geneva and University of Lausanne, Switzerland

Acetylcarnitine is a necessary intermediate in acetate metabolism. Time courses of 13C labeled acetylcarnitine would allow for more detailed mathematical models to quantify mitochondrial oxidation of acetate. Using localized DEPT we monitored 13C enrichment and isotope turnover in glutamate and acetylcarnitine in skeletal muscle in vivo following [2-13C]acetate infusion. Two different modeling approaches were evaluated to determine metabolic fluxes, either with or without the 13C labeling of acetylcarnitine and the enzymatic fluxes of acetylCoA synthesase (ACS) and acetylcarnitine transferase (CAT).

11:36 0540.   
Combined Imaging of Cl- and Na+ at 7 Tesla: First Results in Brain Tumors
Armin M. Nagel1, Reiner Umathum1, Marc-André Weber2,3, Jan-Oliver Neumann4, and Armin Biller5
1Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, 2Diagnostic and Interventional Radiology, University Hospital of Heidelberg, Germany, 3Radiology, German Cancer Research Center (DKFZ), Germany, 4Dpt. of Neurosurgery, University Hospital of Heidelberg, Heidelberg, Germany, 5Dpt. of Neuroradiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Chlorine (Cl-) is the most abundant anion in the human body and is involved in many important physiological processes such as the regulation of the electric excitability and cell migration in cancer. Sodium (Na+) plays also a fundamental role in cellular processes. In this work combined 35Cl and 23Na MRI was performed for the first time in brain tumor patients. In the calculation of the Cl-/Na+ ratio maps differences in the point spread functions of35Cl and 35Na MRI were accounted for. In the tissue affected by the gliomas, the measured Cl-/Na+ ratio was markedly decreased compared to healthy brain tissue.

11:48 0541.   Monitoring Tissue-Engineered Graft Oxygenation In Vivo by Fluorine-19 Magnetic Resonance Spectroscopy
Samuel A Stein1, Bradley P Weegman1, Thomas M Suszynski2, Meri T Firpo3, Melanie L Graham2, Klearchos K Papas4, and Michael Garwood1
1Radiology, University of Minnesota, Minneapolis, MN, United States, 2Surgery, University of Minnesota, Minneapolis, MN, United States, 3Medicine, University of Minnesota, Minneapolis, MN, United States, 4Surgery, University of Arizona, Tucson, AZ, United States

Transplantation of tissue-engineered grafts (TEGs) has the potential to treat numerous debilitating diseases. Non-invasive monitoring of the oxygen partial pressure (pO2) in TEGs is critically important because of the harmful effects of prolonged or even short-term exposure to hypoxia and anoxia. This pilot study evaluated the utility of 19F-MRS in the non-invasive measurement of in vivo pO2 within macroencapsulated TEGs following implantation in the murine model. These preliminary studies confirm that 19F-MRS can be used to non-invasively measure pO2 in vivo within a TEG and suggest that the encapsulated TEG becomes hypoxic 1 week post-transplant despite the oxygen permeable membrane.