ISMRM 21st Annual Meeting & Exhibition 20-26 April 2013 Salt Lake City, Utah, USA

MRS: Normal Metabolism & Systems Under Stress
Monday 22 April 2013
Room 150 AG  16:30 - 18:30 Moderators: Truman R. Brown, Dennis W. J. Klomp

16:30 0111.   
The C57BL/6 Mouse Exhibits Sporadic Congenital Portosystemic Shunts
Cristina Cudalbu1, Valérie A. McLin2, Hongxia Lei1,3, Joao M.N. Duarte1,4, Anne-Laure Rougemont5, Graziano Oldani6,7, Sylvain Terraz8, Christian Toso6, and Rolf Gruetter9,10
1Laboratory for Functional and Metabolic Imaging, Center for Biomedical Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland,2Département de l'Enfant et de l'Adolescent, Unité de Gastroentérologie, Hôpitaux Universitaires de Genève, Geneva, Switzerland, 3University of Geneva, Geneva, Switzerland, 4University of Lausanne, Lausanne, Switzerland, 5Service de Pathologie Clinique, Hôpitaux Universitaires de Genève, Geneva, Switzerland,6Transplantation Division, Department of Surgery, University of Geneva Hospitals, Geneva, Switzerland, 7University of Pavia, Pavia, Italy, 8Unité de radiologie abdominale, Service de Radiologie, Hôpitaux Universitaires de Genève, Geneva, Switzerland, 9Laboratory for Functional and Metabolic Imaging, Center for Biomedical Imaging, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 10University of Lausanne, University of Geneva, Lausanne, Geneva, Switzerland

Portosystemic shunting may be the most significant problem associated with C57BL/6 inbreeding both for its effect on gene expression in the central nervous system and its systemic repercussions.

16:42 0112.   Astrocyte Reactivity Is Associated with Decreased Levels of N-Acetyl-Aspartate in the Absence of Neurodegeneneration in the Rat Brain -permission withheld
Maria-Angeles Carrillo-de Sauvage1,2, Lucile Ben Haim1,2, Julien Valette1,2, and Carole Escartin1,2
1CEA-MIRCen, Fontenay-aux-Roses, France, 2CNRS URA 2210, Fontenay-aux-Roses, France

A decrease in the concentration of the neuronal metabolite NAA is usually interpreted as neuronal degeneration or dysfunction, although the molecular basis is still unknown. Reactive astrocytes are associated with degenerating or dysfunctional neurons and could indirectly modulate brain metabolite concentrations. In this study, we aimed at dissecting the MRS signature associated with astrocyte reactivity per se, using a model of selective astrocyte activation through lentiviral gene transfer of the cytokine CNTF, in absence of detectable effects on neurons. We show that, contrary to the classic interpretation, a decrease in NAA can occur in absence of neurodegeneration

16:54 0113.   7 T 1H Detects Human Brain Gutamate Concentration Changes in Response to Hypoglycemia: A Study of Diabetic Patients with and Without Hypoglycemia Unawareness -permission withheld
Melissa Terpstra1, Amir Moheet1, Anjali Kumar1, Lynn E. Eberly1, Elizabeth Seaquist1, and Gulin Oz1
1University of Minnesota, Minneapolis, MN, United States

Hypoglycemia unawareness (HU) is a condition under which patients with type 1 diabetes (T1D) are unable to sense dangerously low blood glucose levels. Glutamate is thought to be involved in the mechanism of aberrant glucose sensing in HU. The goal of this project was to determine whether human brain glutamate concentrations respond differently to experimentally induced hypoglycemia in patients with T1D and HU than in patients with T1D without HU and healthy controls (n = 5 per group). Human brain glutamate concentration decreased (p ≤ 0.02) after initiation of hypoglycemia in all three study groups.

17:06 0114.   
Early Increases in Glu/Gln, Tau and TCho 1H MRS Resonances in vivo, Anticipate Later Imaging Repercussions of the Cerebral Inflammatory Response in a Mouse Model of LPS-Induced Endotoxemia
Ana Belen Martín-Recuero1, Agnieszka Krzyzanowska2, Pilar López-Larrubia1, Carlos Avendaño2, and Sebastián Cerdán3
1Laboratorio de Modelos Animales, Instituto Investigaciones Biomédicas “Alberto Sols” CSIC-UAM, Madrid, Spain, 2Anatomy, Histology & Neuroscience, Medical School, Autonoma Univ. of Madrid, Spain, Madrid, Spain, 3Laboratorio de Modelos Animales, Instituto de Investigaciones Biomédicas - CSIC, Madrid, Spain

Cerebral inflammation underlies the most morbid and prevalent neurological disorders, including cancer, ischemia or neurodegeneration. However, the inflammatory component remains difficult to differentiate from the intrinsic pathology by most bioimaging methods, since in-vivo biomarkers of the inflammatory phenotype have not been characterized. With this aim, we report a longitudinal MRI and MRS characterization of the cerebral inflammatory component developed after systemic administration of LPS, an inflammation model devoid of additional intrinsic pathologies. Our results revealed that inflammation is characterized by early, severe, spectroscopic changes in Glu/Gln, tCho, Tau and Lac resonances, anticipating those detected later by multi-parametric MRI.

17:18 0115.   
23Na-MRI and EPT: Are Sodium Concentration and Electrical Conductivity at 298 MHz (7T) Related?
Astrid L.H.M.W. van Lier1, Paul W. de Bruin2, Sebastian A. Aussenhofer3, Peter R. Luijten1, Jan J.W. Lagendijk1, Cornelis A.T. van den Berg1, and Andrew G. Webb3
1Imaging Department, UMC Utrecht, Utrecht, Utrecht, Netherlands, 2Radiology, Clinical Physics, LUMC, Leiden, Zuid-Holland, Netherlands, 3Radiology, C.J. Gortercentrum, LUMC, Leiden, Zuid-Holland, Netherlands

The electrical conductivity at the Larmor frequency can be measured with electrical properties tomography (EPT). It is assumed that the conductivity at RF frequencies (>100 MHz) is not affected by impaired ion mobility (e.g. by cell membranes), but only by ion concentration. Comparing EPT-based conductivity maps and 23Na-MR images offers the possibility to investigate this hypothesis in vivo. Based on the graphical analysis of residuals, it is concluded that the conductivity of healthy brain tissue at 298 MHz can be described using a model derived for saline solutions. This might enable direct extraction of sodium concentrations from electrical conductivity images.

17:30 0116.   
Chlorine (35Cl) MRI in Humans: Cl- Alterations Do Not Correspond to Disease-Related Na+ Changes
Armin M. Nagel1, Marc-André Weber2,3, Frank Lehmann-Horn4, Karin Jurkat-Rott4, Alexander Radbruch3,5, Reiner Umathum1, and Wolfhard Semmler1
1Dpt. of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, 2Dpt. of Diagnostic and Interventional Radiology, University Hospital of Heidelberg, Heidelberg, Germany, 3Dpt. of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, 4Division of Neurophysiology, Ulm University, Ulm, Germany, 5Dpt. of Neuroradiology, University Hospital of Heidelberg, Heidelberg, Germany

Chlorine (Cl-) is the most abundant anion in the human body and is involved in many physiological processes. In this work 35Cl images of different pathologies were acquired for the first time in humans. Results were compared to 23Na MRI. 35Cl MRI revealed different signal behavior compared to 23Na MRI. Thus, 35Cl MRI can complement 23Na MRI in clinical research and might enable a better analysis of (patho-)physiological processes in the future.

17:42 0117.   
In Vivo Cardiac 1H MRS, 31P MRS, and MRI in Mouse Models of Increased Fatty Acid Oxidation with and Without Myocardial Lipid Accumulation
Desiree Abdurrachim1, Jolita Ciapaite1, Michel van Weeghel2, Bart Wessels1, Klaas Nicolay1, Sander M. Houten2, and Jeanine J. Prompers1
1Biomedical NMR, Eindhoven University of Technology, Eindhoven, Netherlands, 2Laboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, Netherlands

Using a combination of in vivo 1H MRS, 31P MRS, and MRI, we investigated the relative roles of cardiac lipotoxicity and impaired cardiac energetics in the development of cardiac dysfunction, using mouse models of increased fatty acid oxidation with and without myocardial lipid accumulation. In the mouse model with myocardial lipid accumulation, cardiac energy status was normal, whereas in the mouse model without myocardial lipid accumulation, cardiac energy status was reduced. Interestingly, in both mouse models, a similar degree of cardiac dysfunction was observed, suggesting that myocardial lipid accumulation and disturbances in cardiac energetics independently contribute to reduced cardiac performance.

17:54 0118.   Caloric Restriction Enhances Oxidative Brain Metabolism in Healthy Aging Detected by 1H[13C]MRS
Ai-Ling Lin1,2, Daniel Coman3, Lihong Jiang3, Douglas L. Rothman3, and Fahmeed Hyder3
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, 2Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, 3Magnetic Resonance Research Center, Yale University, New Haven, CT, United States

Caloric restriction seems to increase the lifespan in rodents. In the study, we used in vivo 1H[13C] MRS to characterize the effect of caloric restriction on rates of neuronal TCA cycle flux (VTCA,N) and total glutamatergic neurotransmission flux (Vcyc(tot)) from the glutamate and glutamine cycle in aged rats (24 months). We found that caloric restricted rats had significantly higher VTCA,N and Vcyc(tot) relative to controls, suggesting that caloric restricted rats had enhanced neuronal metabolism and that was similar to younger aged rats. This indicates that caloric restriction may delay brain age-related metabolic reduction in rodents.

18:06 0119.   Rates of Human Hepatic Oxidative Metabolism Estimated in Vivo Using a Novel 13C-MRS Method
Douglas E. Befroy1,2, Nimit Jain3, Kitt Falk Petesen2, Gerald I. Shulman2,4, and Douglas L. Rothman3,5
1Diagnostic Radiology, Yale University, New Haven, CT, United States, 2Internal Medicine, Yale School of Medicine, New Haven, CT, United States, 3Diagnostic Radiology, Yale School of Medicine, New Haven, CT, United States, 4Howard Hughes Medical Institute, Yale School of Medicine, New Haven, CT, United States,5Biomedical Engineering, Yale University, New Haven, CT, United States

We have previously demonstrated that oxidative metabolism can be observed in human liver in vivo using 13C-MRS in conjunction with a novel 13C-labeling strategy. In this study we describe the implementation of this methodology to determine rates of hepatic TCA cycle flux and anaplerosis in healthy individuals. To accurately simulate the kinetics of 13C-label turnover and generate robust estimates of these fluxes we also developed a model of hepatic metabolism that includes phenomena which distinguish the liver from other tissues. These studies provide the first direct estimates of liver TCA cycle flux and anaplerosis in vivo.

18:18 0120.   
Acetylcarnitine Turnover in Rat Skeletal Muscle Measured in Vivo Using Localized 13C NMR at 14.1 T -permission withheld
Jessica A. M. Bastiaansen1, Joao M.N. Duarte2,3, Arnaud Comment4, and Rolf Gruetter5,6
1Laboratory of Functional and Metabolic Imaging, EPFL, Lausanne, Switzerland, 2Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 3Department of Radiology, University of Lausanne, Lausanne, Switzerland, 4Institute of Physics of Biological Systems, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 5Laboratory of Functional and Metabolic Imaging, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 6Department of Radiology, University of Lausanne and Geneva, Lausanne and Geneva, Switzerland

Acetate has been widely used as a metabolic probe for measuring TCA cycle kinetics in vivo in skeletal muscle. To cross the mitochondrial membrane, acetate needs to be transformed into acetylcarnitine, a metabolite which has not been observed in vivo using non-hyperpolarized 13C MRS. The aim was to detect the [2-13C]acetylcarnitine resonance in vivo using localized DEPT at 14.1T. This study demonstrates that at high field using a polarization transfer technique acetylcarnitine can be observed. This allows for a more detailed characterization of acetate oxidation in skeletal muscle in vivo and in studies of metabolic disorders where carnitine deficiency occurs.