Non-Proton MRS

Wednesday 14 May 2014

Yunjung Lee¹ and Hyeonjin Kim^1,2
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.

Jose Luis Izquierdo Garcia¹, Pia Eriksson¹, Cai Larry¹, Myriam Chaumeil¹, Russell O Pieper², Joanna J Phillips², and Sabrina M Ronen^1
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.

Andrew Bresnen¹ and Timothy Q. Duong^1
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.

Marta Lai¹, Bernard Lanz^1,2, Carola Jaquelina del Carmen Romero^1,3, Cristina Cudalbu³, and Rolf Gruetter^1,4
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.

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 Bachoo^2
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

Ming Lu¹, Xiao-Hong Zhu¹, Yi Zhang¹, Gheorghe Mateescu^2,3, and Wei Chen^1
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, -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 -ketoglutarate/glutamate exchange rate can be achieved in animal and human brains.

Sergey Cheshkov^1,2, Ivan Dimitrov^1,3, Karlos Moreno¹, and Craig Malloy^1,2
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.

Jessica A.M. Bastiaansen¹, Joao M.N. Duarte¹, and Rolf Gruetter^1,2
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).

Armin M. Nagel¹, Reiner Umathum¹, Marc-André Weber^2,3, Jan-Oliver Neumann⁴, and Armin Biller^5
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.

Samuel A Stein¹, Bradley P Weegman¹, Thomas M Suszynski², Meri T Firpo³, Melanie L Graham², Klearchos K Papas⁴, and Michael Garwood^1
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.