ISMRM 24th Annual Meeting & Exhibition • 07-13 May 2016 • Singapore

Scientific Session: Brain Metabolism

Monday, May 9, 2016
Room 300-302
14:15 - 16:15
Moderators: Lindy Rae, Eric Schrauben

Dietary Restriction Improved Memory and Neuronal Metabolism in AßPP-PS1 Mouse Model of Alzheimer’s Disease: A 1H-[13C]-NMR Study
Anant Bahadur Patel1 and Kamal Saba1
1NMR Microimaging and Spectroscopy, CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India
Alzheimer's disease (AD) is the most common neurodegenerative disorders. Currently no effective treatment available for AD. Dietary restriction (DR) has been shown to improve longevity in rodents. In the present study, we evaluated the effects of DR on memory and brain energy metabolism in AβPP-PS1 mouse model of AD using 1H-[13C]-NMR spectroscopy in conjunction with infusion of [1,6-13C2]glucose. Our findings suggest that DR intervention had improved the memory and the neuro-metabolic activity in the AD mice.

A 1H-[13C]-NMR Study for Understanding Antidepressant Action of Lanicemine in Chronic Unpredictable Mild Stress Model of Depression
Pravin K Mishra1 and Anant Bahadur Patel1
1NMR Microimaging and Spectroscopy, CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India
Though, ketamine possess rapid antidepressant properties, its use is limited due to addictive and psychotomimetic properties. In the current study, we have evaluated the antidepressant activity of lanicemine in CUMS model of depression by 1H-[13C]-NMR spectroscopy together with infusion of [1,6-13C2]glucose. Exposure of lanicemine restored behavioral phenotype and activity of excitatory and inhibitory neurons in depression.

Brain Glycogen Supercompensation: A Role in the Development of Hypoglycemia Unawareness?
Gulin Oz1, Mauro DiNuzzo2, Anjali Kumar3, Amir Moheet3, Kristine Kubisiak4, Lynn E. Eberly4, and Elizabeth R. Seaquist3
1Radiology, Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, 2Museo storico della fisica e Centro di studi e ricerche Enrico Fermi, Rome, Italy, 3Medicine, University of Minnesota, Minneapolis, MN, United States, 4Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, United States
Supercompensated brain glycogen levels may contribute to the development of hypoglycemia associated autonomic failure (HAAF) following recurrent hypoglycemia (RH) by providing energy for the brain during subsequent periods of hypoglycemia. To assess the role of glycogen supercompensation in the generation of HAAF, we estimated the level of brain glycogen supercompensation following RH using 13C MRS and compared it to that following acute hypoglycemia (AH). Glycogen levels were found to increase after both AH and RH, but to a lesser extent after RH. These data suggest that glycogen supercompensation may be an epiphenomenon of HAAF.

In vivo detection of hypothalamic glucose metabolism in HFD and regular fed mice
Blanca Lizarbe1, Antonie Cherix1, Lijing Xin2, Hongxia Lei2,3, and Rolf Gruetter1,3,4
1Laboratory for Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 2Animal imaging and technology core (AIT), Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, Lausanne, Switzerland, 3Department of Radiology, University of Geneva, Geneva, Switzerland, 4Department of Radiology, University of Lausanne, Lausanne, Switzerland
Obesity is a pandemic syndrome that leads to reduced life expectancy, increasing the risk of heart disease, type-2 diabetes and some type of cancers.  Noteworthy, to understand the mechanisms of obesity onset and development, several animal models, such as administration high fat diets, have been developed. We used 1H-[13C] MRS methods in regular and in high fat diet fed mice to investigate the effects of high caloric diets and obesity in the hypothalamus, its effects in glucose metabolism and metabolic fluxes in neurons and glia. We found differences that suggest impaired glucose metabolism in the hypothalamus of obese mice.

Amide proton signals as pH indicator for in vivo MRS and MRI of the brain – Responses to hypercapnia and hypothermia
Takashi Watanabe1, Jens Frahm1, and Thomas Michaelis1
1Biomedizinische NMR Forschungs GmbH, Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany
Using proton MRS/MRI of mouse brain at 9.4 T, this work provides the first in vivo evidence of concurrent pH-dependent changes of amide signals and related metabolic responses to hypercapnia and hypothermia. During hypercapnia, amide MRS signals of glutamine and of unspecific compounds increase by ≥50% at 37°C and 22°C. They are strongly correlated with intracellular pH determined from a shift in creatine phosphokinase equilibrium. In MRI, saturation transfer to water protons alters signal intensities in dependence on pH and temperature. Irradiation of aliphatic compounds at -3.5 ppm frequency offset from water predominantly saturates lipids and water associated with myelin.

Assessing metabolic and structural alterations of brain cells in the APP/PS1/tauP301L mouse model of Alzheimer’s disease using MRS and diffusion-weighted MRS in vivo
Clemence Ligneul1,2, Marco Palombo1,2, Juliette Le Douce1,2, Pierrick Jego1,2, Martine Guillermier1,2, Gilles Bonvento1,2, and Julien Valette1,2
1CEA/DSV/I2BM/MIRCen, Fontenay-aux-Roses, France, 2CNRS Université Paris-Saclay UMR 9199, Fontenay-aux-Roses, France
In this work we use in vivo MRS and diffusion-weighted MRS to detect alterations in cellular metabolism and structure in a triple transgenic APP/PS1/tauP301L mouse model of Alzheimer’s disease. We are able to detect massive remodeling of metabolic content in the hippocampus, as well as subtle but significant variations in diffusion properties of astrocytic metabolites. These results are essentially consistent with the metabolic and structural signature of activated astrocyte, a cell status represented around amyloid plaques.

Brain Sodium MRI depicts upper motor neuron involvement in Amyotrophic Lateral Sclerosis patients
Aude-Marie Grapperon1, Adil Maarouf2,3, Annie Verschueren1, Amandine Sevy1, Elisabeth Soulier2, Sylviane Confort-Gouny2, Patrick Viout2, Jean-Philippe Ranjeva2, Maxime Guye2,3, Sharham Attarian1, and Wafaa Zaaraoui2
1APHM, Hôpital Timone, Pôle Neurosciences, Marseille, France, 2CRMBM - CNRS - Aix-Marseille Université, Marseille, France, 3APHM, Hôpital Timone, CEMEREM, Marseille, France
Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease that involves the death of upper (in brain) and lower (in spine) motor neurons. As conventional MRI failed to show brain motor neurons impairment in ALS, advanced techniques are needed to improve the diagnosis of the disease and monitor its progression. 23Na brain MRI was performed to 4 ALS patients and showed accumulation of sodium in the primary motor areas in the 3 patients presenting with clinical brain motor neuron signs. Besides, more patients were clinically affected, more the sodium accumulation was extended. In conclusion, sodium accumulation, which is an indicator of neuronal injury, could be a marker of ALS diagnosis and disease progression.

Modulations of cerebral TCA cycle activity studied by hyperpolarized Acetate 13C MRS - Permission Withheld
Elise Vinckenbosch1, Mor Mishkovsky1, Arnaud Comment2, and Rolf Gruetter1,3
1Laboratory of functional and metabolic imaging, EPFL, Lausanne, Switzerland, 2Institute of Physics of Biological Systems, EPFL, Lausanne, Switzerland, 3Department of Radiology, University of Lausanne and Geneva, Lausanne, Switzerland
Hyperpolarized [1-13C] acetate enables for in vivo detection of 2-oxoglutarate, a tricarboxylic acid (TCA) cycle intermediate, in intact brain at high field. The aim of this study is to examine saturation substrate dose conditions and to compare it with a partially inhibited TCA cycle model. We conclude that 2-oxoglutarate production rate can be calculated as a function of varying substrate concentrations and is affected as well as the cerebral acetate kinetics by TCA cycle activity modulations.

Brain lactate concentration falls in response to hypoglycemia in type 1 diabetes patients with impaired awareness of hypoglycemia
Evita Wiegers1, Hanne Rooijackers2, Cees Tack2, Arend Heerschap1, Bastiaan de Galan2, and Marinette van der Graaf1,3
1Radiology and Nuclear Medicine, Radboud umc, Nijmegen, Netherlands, 2Internal Medicine, Radboud umc, Nijmegen, Netherlands, 3Pediatrics, Radboud umc, Nijmegen, Netherlands
TThe effect of hypoglycemia on cerebral lactate concentration was assessed in patients with type 1 diabetes (T1DM) and impaired awareness of hypoglycemia (IAH), patients with normal awareness of hypoglycemia (NAH) and in healthy subjects. Brain lactate concentrations were determined during stable euglycemic and stable hypoglycemic conditions using a J-editing semi-LASER 1H-MRS sequence at 3T. We found a 20% decrease in brain lactate concentration in T1DM patients with IAH in response to hypoglycemia, which may reflect increased lactate oxidation. No changes in cerebral lactate concentrations were observed in the other two groups.

Differential Metabolic Profiles in Rat Retrosplenial Cortex, Cingulate Cortex and Medial Prefrontal Cortex: Relationship with Cytoarchitecture and Functional Implications
Hui Zhang1 and Hao Lei1
1National Center of Magnetic Resonance in Wuhan, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, China, People's Republic of
In this study, we measured regional neurochemical variations in rat prelimbic cortex (PrL)/infralimbic cortex (IL), cingulate cortex (Cg) and retrosplenial cortex (RSC)  with in vivo 1H-MRS at 7T. It was found that the regional metabolic variations follow cytoarchitectural/receptor-architectonical organization in these brain regions.

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