MRS: Normal Metabolism & Systems Under Stress

Monday 22 April 2013

Cristina Cudalbu¹, Valérie A. McLin², Hongxia Lei^1,3, Joao M.N. Duarte^1,4, Anne-Laure Rougemont⁵, Graziano Oldani^6,7, Sylvain Terraz⁸, Christian Toso⁶, and Rolf Gruetter^9,10
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.

Maria-Angeles Carrillo-de Sauvage^1,2, Lucile Ben Haim^1,2, Julien Valette^1,2, and Carole Escartin^1,2
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

Melissa Terpstra¹, Amir Moheet¹, Anjali Kumar¹, Lynn E. Eberly¹, Elizabeth Seaquist¹, and Gulin Oz^1
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.

Ana Belen Martín-Recuero¹, Agnieszka Krzyzanowska², Pilar López-Larrubia¹, Carlos Avendaño², and Sebastián Cerdán^3
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.

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. Webb^3
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.

Armin M. Nagel¹, Marc-André Weber^2,3, Frank Lehmann-Horn⁴, Karin Jurkat-Rott⁴, Alexander Radbruch^3,5, Reiner Umathum¹, and Wolfhard Semmler^1
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.

Desiree Abdurrachim¹, Jolita Ciapaite¹, Michel van Weeghel², Bart Wessels¹, Klaas Nicolay¹, Sander M. Houten², and Jeanine J. Prompers^1
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.

Ai-Ling Lin^1,2, Daniel Coman³, Lihong Jiang³, Douglas L. Rothman³, and Fahmeed Hyder^3
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.

Douglas E. Befroy^1,2, Nimit Jain³, Kitt Falk Petesen², Gerald I. Shulman^2,4, and Douglas L. Rothman^3,5
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.

Jessica A. M. Bastiaansen¹, Joao M.N. Duarte^2,3, Arnaud Comment⁴, and Rolf Gruetter^5,6
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.