Spectroscopy Quantification & Metabolism
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Tuesday May 10th
Room 513A-D  16:00 - 18:00 Moderators: Ulrike Dydak and Ricahrd Edden

16:00 304.   Measurement of elevated 2-hydroxyglutaric acid in brain tumors by difference editing at 3T in vivo 
Changho Choi1, Sandeep Ganji1, Zoltan Kovacs1, Ralph DeBerardinis1, and Elizabeth Maher1
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.

16:12 305.   Elucidating Brain Metabolism by Dynamic 13C Isotopomer Analysis 
Alexander A Shestov1, Dinesh K Deelchand1, Kamil Ugurbil1, and Pierre-Gilles Henry1
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.

16:24 306.   Increased brain monocarboxylic acid transport and metabolism in T1DM patients with hypoglycemia unawareness 
Henk M. De Feyter1, Barbara I Gulanski2,3, 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 Sherwin2
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.

16:36 307.   Brain Glycogen Content and Metabolism in Type 1 Diabetes 
Gulin Oz1, Nolawit Tesfaye1, Anjali Kumar1, Dinesh K. Deelchand1, and Elizabeth R. Seaquist1
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.

16:48 308.   Definition of the macromolecular baseline based on T1 as well as T2 properties 
Daniel Guo Quae Chong1, Christine S Bolliger2, Johannes Slotboom3, Chris Boesch2, and Roland Kreis2
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.

17:00 309.   Metabolite concentration changes during visual stimulation using functional Magnetic Resonance Spectroscopy (fMRS) on a clinical 7T scanner 
Benoit Michel Schaller1, Ralf Mekle2, Lijing Xin3, and Rolf Gruetter1,4
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.

17:12 310.   Classification of single voxel 1H spectra of brain tumours using LCModel 
Felix Raschke1, Elies Fuster-Garcia2,3, Kirstie Suzanne Opstad1, and Franklyn Arron Howe1
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.

17:24 311.   Investigating the metabolic changes due to visual stimulation using functional proton magnetic resonance spectroscopy at 7T 
Yan Lin1,2, Mary C Stephenson1, Samuel J Wharton1, Lijing Xin3, Olivier E Mougin1, Antonio Napolitano4, and Peter G Morris1
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.

17:36 312.   Quantitative MRS of Ovaries and Ovarian Masses at 3T: Methodology and Initial Findings 
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.

17:48 313.   Hepatic glycogen metabolism in mice by in vivo 13C MRS at 14T 
Christine Nabuurs1, Frederic Preitner2, Bernard Thorens2, and Rolf Gruetter3
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.