Changho Choi¹, Sandeep Ganji¹, Zoltan Kovacs¹, Ralph DeBerardinis¹, and Elizabeth Maher^1
1University of Texas Southwestern Medical Center, Dallas, Texas, United States

Recent mass spectroscopy studies in-vitro and ex-vivo indicated that a fraction of gliomas contain mutations of isocitrate dehydrogenase-1 and -2, causing accumulations of 2-hydroxyglutaric acid (2HG). Here, we present in vivo detection of 2HG in human brain tumors by means of difference editing at 3T. The C2-proton resonance of 2HG at 4.02 ppm was edited using a 20 ms Gaussian radio-frequency (RF) pulse for selective 180„a rotation of the its coupling partners at ~1.9 ppm. In vivo measurement was conducted in various tumors. The results indicated that 2HG is elevated to 2 - 8 mM in low-grade gliomas and secondary glioblastomas.

Alexander A Shestov¹, Dinesh K Deelchand¹, Kamil Ugurbil¹, and Pierre-Gilles Henry^1
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States

Information from ¹³C isotopomers, which appear as multiplets in ¹³C NMR spectra can be measured and quantified in vivo. We show here that using this additional information on isotopomers along with an extended brain bionetwork model allows accurate fitting of the experimental dynamic ¹³C isotopomer turnover curves.

Henk M. De Feyter¹, Barbara I Gulanski^2,3, Kathleen A Page⁴, Anne Howard O'Connor², Ellen V Hintz², Susan M Harman², Renata Belfort De Aguiar², Graeme F Mason², Douglas L. Rothman², and Robert S Sherwin^2
1Diagnostic Radiology, Yale University, New Haven, CT, United States, ²Yale University, ³VA Connecticut Healthcare System, West Haven, ⁴USC Keck School of Medicine, Los Angeles, USA

Previously we showed in well-controlled type 1 diabetes patients increased brain metabolism of acetate, a monocarboxylic acid (MCA) transported over the blood-brain barrier via MCT1. However, it is unclear whether these adaptations are related to frequency and severity of hypoglycemic episodes or type 1 diabetes per se. We therefore investigated the relationship between cortical metabolic adaptations and i) severity of antecedent hypoglycemia unawareness and ii) counterregulatory response to acute hypoglycemia using ¹³C MRS and infusion of [2-¹³C]-acetate and show how the severity of hypoglycemia unawareness and lack of counterregulatory response is independent of diabetes and correlates with the degree of MCA transport and metabolism.

Gulin Oz¹, Nolawit Tesfaye¹, Anjali Kumar¹, Dinesh K. Deelchand¹, and Elizabeth R. Seaquist^1
1University of Minnesota, Minneapolis, MN, United States

Supercompensated brain glycogen levels may contribute to the development of hypoglycaemia unawareness in patients with type 1 diabetes (T1D) by providing energy for the brain during periods of hypoglycaemia. To determine if brain glycogen content is higher in patients with T1D and hypoglycaemia unawareness, brain glycogen content and turnover was measured in 5 patients and 5 age/gender/BMI matched healthy controls using ¹³C MRS and IV infusion of [1-¹³C]glucose followed by [1-¹²C]glucose for a total of 50h. A strong trend for lower glycogen levels in patients than controls (p=0.05) was observed, refuting supercompensated glycogen levels in T1D and hypoglycaemia unawareness.

Daniel Guo Quae Chong¹, Christine S Bolliger², Johannes Slotboom³, Chris Boesch², and Roland Kreis^2
1Dept. of Diagnostic, Interventional and Pediatric Radiology (DIPR), Inselspital, Bern, Switzerland, ²Dept. of Clinical Research, University of Bern, Bern, Switzerland,³Institute for Diagnostic and Interventional Neuroradiology, Inselspital, Bern, Switzerland

Macromolecule baseline (MMBl) determination have usually been done with inversion recovery or saturation recovery techniques. This abstract presents an alternative using both T1 and T2 information by combining inversion recovery and 2D JPRESS spectra iteratively. Part of the study involves ensuring repeatability and the result suggests that MMBl has inter-individual variability.

Benoit Michel Schaller¹, Ralf Mekle², Lijing Xin³, and Rolf Gruetter^1,4
1Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Vaud, Switzerland, ²Physikalisch-Technische Bundesanstalt, Berlin, Germany, ³Department of Radiology, University of Lausanne, Lausanne, Switzerland, ⁴Department of Radiology, Universities of Lausanne and Geneva, Switzerland

Functional MR Spectroscopy allows direct measurement of low concentrated metabolites with small concentration changes (<0.2µmol/g) during neuronal activation providing insight into brain metabolism. In this study, the inter-subject analysis revealed an increase of [Lac] of 20±3%, [Glu] of 10±5% and a decrease of [Asp] of 5±4% in the visual cortex during the activation. The use of SPECIAL sequence at 7T yielded increased SNR compared to STEAM providing a twofold time resolution for the time courses of different metabolites concentration (Lac and Glu). Fewer scans had to be averaged to enable reliable metabolite quantification.

Felix Raschke¹, Elies Fuster-Garcia^2,3, Kirstie Suzanne Opstad¹, and Franklyn Arron Howe^1
1Division of Clinical Science, St George’s University of London, London, United Kingdom, ²IBIME and ITACA, Universidad Politécnica de Valencia, Valencia, Spain, ³Universitat Internacional Valenciana, Valencia, Spain

This study presents a novel method for the direct classification of single voxel 1H MR spectra of brain tumours using the widespread analysis tool LCModel. LCModel is designed to estimate individual metabolite proportions by fitting a linear combination of metabolite spectra to an in vivo MR spectrum, but here is used to fit representations of complete tumour spectra. Classification according to the highest estimated tumour proportion in a test set of 46 spectra comprising high grade gliomas, low grade gliomas and meningiomas, LCModel gives a classification accuracy of 93% compared to 95% by the INTERPRET Decision Support System.

Yan Lin^1,2, Mary C Stephenson¹, Samuel J Wharton¹, Lijing Xin³, Olivier E Mougin¹, Antonio Napolitano⁴, and Peter G Morris^1
1Sir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom, ²Medical Imaging Department, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, China, People's Republic of, ³Laboratory of Functional and Metabolic Imaging, Ecole Poly technique Federale de Lausanne, Lausanne, Switzerland, ⁴Academic Radiology, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom

Previous functional proton MRS studies of the activated human brain at 7T investigated the changes in the levels of Lac, Glu, Asp and Glc, these related mainly to oxidative energy metabolism. Our results demonstrate the changes in Glu (increased by 2%¡À1%), Gln (decreased by 5%¡À3%), Asp(decreased by 9%¡À6%), Lac(increased by 9%¡À6%), Glc (decreased by 30%¡À14%), GSH (increased by 7%¡À2%), and Gly (decreased by 19%¡À5%), in response to visual stimulation. On the basis of these results from the visual cortex, we propose an increase in oxidative metabolism, excitatory neurotransmitter cycling and GSH synthesis, possibly related to Glu clearance and ROS detoxification.

Patrick J Bolan¹, Jori S Carter², Navneeth Lakkadi¹, and Levi S Downs Jr.^2
1Radiology/CMRR, University of Minnesota, Minneapolis, MN, United States, ²Obstetrics, Gynecology, and Women’s Health, University of Minnesota, Minneapolis, MN, United States

This work describes the development of a methodology for performing quantitative ¹H MRS in ovarian masses and normal ovaries at 3T and reports the initial findings in 68 spectra. MRS performance varied depending on the structure measured: healthy ovaries had low SNR due to small size, cystic regions had low metabolic content, and solid regions regularly showed a total choline (tCho) resonance and occasionally other metabolites including creatine, glycine, and an unidentified 2.05ppm resonance. The new quantification method, which uses T₂-corrected water as an internal reference, found tCho ranging from 0.2-3.4 mmol/kg in solid regions.

Christine Nabuurs¹, Frederic Preitner², Bernard Thorens², and Rolf Gruetter^3
1CIBM, Hôpitaux Universitaires de Genève (HUG), Lausanne, Switzerland, ²Mouse Metabolic Facility, Center for Integrative Genomics, UNIL, Lausanne, Switzerland,³Laboratory of Functional and Metabolic Imaging (LIFMET), l'Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland

Contributions of direct and indirect glycogen synthesis in liver tissue can be determined by ₁₃C MRS upon labeled glucose infusion. We optimized a protocol for in vivo MRS at 14T in mouse liver to study the incorporation of ₁₃C into different positions of glycogen by overcoming the large bandwidth needed for simultaneous detection of signals with a chemical shift difference of 6kHz by applying interleaved transmitter frequencies. This allowed for sufficient time resolution and omits signal losses and the need for pulse shape corrections when studying alternative pathways of glycogen synthesis in mouse models with disorders in hepatic carbohydrate metabolism.