MRS of Animal Brain

Room 713 A/B


Chairs: Jun Shen and Ivan Tkac


Prog #

14:00  113.  In Vivo High Resolution Magnetic Resonance Spectroscopy of the Adult Zebrafish Brain at 9.4T

Samira Kabli1, Herman P. Spaink1, Huub J. M de Groot1, A Alia1

1Leiden University, Leiden, Netherlands

Zebrafish is increasingly used as model organism for understanding brain diseases especially due to similar organization of brain components as that of human. In this study we optimized ο MRI and localized 1H MRS sequences at 9.4T to get metabolic profile of the zebrafish brain in vivo.  A high resolution spectrum was obtained from a voxel as small as 3.3 οl placed in the middle of the zebrafish brain which gave excellent separation of resonances from various brain metabolites. Our study suggests that zebrafish brain has similar metabolite profile as that of human brain which proves zebrafish as a good model organism for human brain disorders

14:12  114. Neurochemical Profile of Hippocampal-Specific Iron Transporter Slc11a2 (DMT-1) Knock-Out Mice

Ivan Tkac1, Erik S. Carlson1, Anna Petryk1, Michael K. Georgieff1

1University of Minnesota, Minneapolis, Minnesota, USA

In vivo 1H NMR spectroscopy at 9.4 T was used to investigate neurochemical changes in hippocampus of CamKII α -cre/S1c11a2 flox/flox double-mutant mice with knock-out of the iron transporter Slc11a2 in forebrain neurons. Iron content was selectively reduced in hippocampus by 40% in knock-out (KO) relative to wild type (WT) mice. Behavioral tests showed cognitive deficit of KO mice relative to WT. Of all 17 metabolites quantified in hippocampus only Lac levels were significantly reduced in KO mice relative to WT controls, which may indicate reduced energy production.

14:24 115. Metabolic Changes in Rat Frontal Cortex After Injection of Pentylenetetrazole Measured by Proton MR Spectroscopy at 9.4T

Shaolin Yang1, D. Bruce Vaupel1, Hanbing Lu1, Thomas J. Ross1, William Rea1, Steven M. Demny1, Elliot A. Stein1, Yihong Yang1

1National Institute on Drug Abuse, NIH, Baltimore, Maryland, USA

Seizures were induced in rats by intraperitoneal injection of pentylenetetrazole (PTZ, 70 mg/kg). The time series of metabolite concentrations in the frontal cortex of adult rat brain were measured in vivo before and after the injection by localized 1H MRS spectroscopy at 9.4T (3 time points before the injection and 4 time points after, 25 minutes for each time point). Compared to the baseline levels, the average concentrations of glutamine (Gln) and -aminobutyric acid (GABA) (n = 7) significantly increased post injection but reached peaks at different time.

14:36 116. Cerebral Activation by Fasting Results in Lactate Accumulation in the Hypothalamus

Ines R. Violante1, Jelena Anastasovska2, Gina J. Sanchez-Canon2, Tiago B. Rodrigues1, Laura Nieto1, Stephen R. Bloom3, James R. Parkinson3, Jimmy Bell2, Sebastian Cerdan1

1CSIC, Madrid, Spain; 2Hammersmith Hospital, London, UK; 3Imperial College, London, UK

We investigate the neuroglial metabolic interactions underlying appetite control during the feeding/fasting cycles. We administered an i.p. injection of (1-13C) glucose (20 mol/g) to C57BL/6 mice, fixed the brain with high power microwaves (5kW), dissect the hypothalamus from the remaining cerebral structures and analyzed the 13C distribution in these regions by 13C HRMAS. Our results indicate that cerebral activation by fasting results in increased (3-13C) lactate and decreased (4-13C) glutamate levels in the hypothalamus. This finding suggests that the activation by fasting occurs most probably through the Astrocyte to Neuron Lactate Redox Shuttle, as in other sensorial activation processes.

14:48 117. Preliminary Studies of MDMA Induced Brain Hyperthermia Using Spectroscopic Imaging and 1H-[13C]MRS

Lihong Jiang1, Robin A. de Graaf, Kevin L. Behar

1Yale University, New Haven, Connecticut, USA

In this study, we combined brain temperature mapping using the temperature-dependent frequency shift of water relative to NAA with 1H-[13C] MRS measurements of 13C turnover following acute MDMA-induced hyperthermia. The SI temperature map showed regional differences in temperature elevation, lower values in cortex and higher values in hippocampus. Glutamate and glutamine 13C turnover from [1,6-13C] glucose appeared faster during MDMA hyperthermia suggest increased oxidative metabolism.

15:00   118.  Overcoming Experimental Challenges in the Assessment of Metabolic Fluxes with [1,6-13C-2]glucose in Mouse Brain

Christine Nabuurs1, Dennis Klomp1, Andor Veltien1, Bart Van de Bank1, Arend Heerschap1

1Radboud University Nijmegen Medical Center, Nijmegen, Netherlands

One of the largest hurdles in the assessment of metabolic conversion by MRS with 13C labeled glucose infusion in mouse brain, is the determination of time resolved 13C  enrichment of labeled metabolites in vivo during the MR experiment. These preliminary results demonstrate a coil setup and method, that allows for detection of glutamate and glutamine signals using POCE and DEPT methods sequentially to obtain spectra in the same VOI in a mouse brain. This enables both good separate detection of labeled metabolites and evaluation of isotopic enrichment.

15:12 119. NMR Investigations of Acetate Transport and Metabolism in the Rat Brain In Vivo

Anant Bahadur Patel1, 2, Robin A. de Graaf1, Douglas L. Rothman1, Robert G. Shulman1, Kevin L. Behar1, Graeme F. Mason1

1Yale University School of Medicine, New Haven, USA; 2Centre for Cellular and Molecular Biology, Hyderabad, India

In the present study we investigated transport and metabolism of acetate in rat brain in vivo. Cerebral metabolite levels and 13C labeling were measured in vivo at 7 Tesla using 1H-[13C]-NMR spectroscopy in halothane-anesthetized rats receiving intravenous infusions of [2-13C]acetate. Steady-state brain acetate increased linearly with plasma level, whereas Gln-C4 labeling, which reflects the oxidation of acetate by the astroglial TCA cycle, reached saturation for plasma levels 15 mM. The maximum rate of acetate utilization was ~14% of total (neuronal + glial) oxidative metabolism.

15:24 120.
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Cerebral Phosphate Metabolite Profiles and Their Differentiation in Human, Cat and Rat Brains: A Comparison Study of In Vivo 31P MRS at High Fields

Xiao-Hong Zhu1, Fei Du1, Yi Zhang1, Wei Chen1

1Center for Magnetic Resonance Research, Minneapolis, Minnesota, USA

In vivo 31P MRS provides useful measures of a large number of cerebral phosphate metabolites and tissue pH. It is particularly important for studying the ATP metabolism and bioenergetics in the brain noninvasively. The reliability of 31P MRS measurement can be significantly improved at high field. We have conducted a study to determine the brain phosphate metabolite profiles in human and two animal species of cat and rat at high fields (7-9.4T). Significant differences were found in the measured metabolite concentrations and tissue pH among the human and animal brains. Our results provide the standard phosphate metabolite profiles of the healthy human, cat and rat brains. This information should be valuable for cerebral metabolic study in these species, especially when comparing physiology versus pathology states in a specific brain of interest.

15:36 121. In Vivo High Resolution Localized Two Dimensional Magnetic Resonance Spectroscopy in Mouse Brain

Niels Braakman1, Thomas Oerther2, Huub de Groot1, A Alia1

1Leiden University, Leiden, Netherlands; 2Bruker BioSpin GmbH, Rheinstetten, Germany

Localized two-dimensional magnetic resonance spectroscopy (2D MRS) is revolutionizing the in vivo studies of brain metabolites due to improved spectral resolution and unambiguous assignment opportunities. Despite the fact that there are large numbers of transgenic mouse models available for neurological disorders, localized 2D MRS has not yet been implemented in the mouse brain due to size constraints. In this study we optimized a localized 2D proton chemical shift correlated spectroscopic sequence at 9.4T to obtain highly resolved 2D spectra from localized regions in the mouse brain in vivo. To our knowledge this is the first in vivo application of 2D MRS in mouse brain. The L-COSY method yields consistent, reproducible results, and thus allows the clear and unambiguous identification of multiple brain metabolites from a single measurement. Such information will prove invaluable in future studies of brain disorders in mouse models.

15:48 122.
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Examining Neuro-Metabolic Correlations Between Resting Rat Brain Activity and Cerebral Metabolite Contents/Metabolic Rates: A 1H/31P MRS Comparison Study

Fei Du1, Yi Zhang1, Xiao-Hong Zhu1, Wei Chen1

1University of Minnesota, Minneapolis, Minnesota, USA

Increases in neuronal activity are accompanied by elevated cerebral metabolic rates of glucose and oxygen consumption (CMRglc, CMRO2) at the activated sites. The end result of glucose and oxygen consumptions is the production of ATP molecules in mitochondria through ATPase. ATP is the fundamental cellular energy currency, and its hydrolysis to inorganic phosphate (Pi) and ADP is coupled to all energy requiring process in the cells. It is, thus, interesting to understand the neuro-metabolic coupling in the brain. In this comparative study, we investigated the correlations between the varied EEG activity through changing the anesthesia depth and the cerebral metabolite concentrations and metabolic rates which can be measured by in vivo 31P and/or 1H MRS. We found that the ATP and glucose metabolic rates are more closely coupled with the varied EEG activity in the resting rat brain as compared to steady-state metabolite concentrations. Thus, the imaging of these rates should provide sensitive and quantitative measures of brain bioenergetics associated with neuronal activity. Finally, this comparison study also supports a tight neuro-metabolic coupling in the rat brain.