| Neurochemical Modeling & Profiling of Brain Metabolism |
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Tuesday 21 April 2009 |
| Room 311 |
16:00-18:00 |
Moderators: |
In-Young Choi and Ivan Tkac |
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16:00 |
347. |
Multimodal NMR Assessment of
Erythropoietin as a Neuroprotective Agent Following
Hypoxia-Ischemia on P3 Pup Rat Brain |
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Yohan van de Looij1,2,
Alexandra Chatagner1, Nicolas Kunz1,2,
Petra S. Hüppi1, Rolf Gruetter3,4,
Stéphane V. Sizonenko1
1Division of Child Growth & Development,
Department of Pediatrics, University of Geneva,
Geneva, Switzerland; 2Laboratory for
Functional and Metabolic Imaging, Ecole
Polytechnique Fédérale de Lausanne, Lausanne,
Switzerland; 3Laboratory for Functional
and Metabolic Imaging, Ecole Polytechnique Fédérale
de Lausanne , Lausanne, Switzerland; 4Department
of Radiology, University of Geneva and Lausanne,
Switzerland |
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The 3-day old rat (P3)
shares some similarities in terms of cerebral
development to the very preterm infant. Animal
models of periventricular leukomalacia (most
important cerebral alteration after premature birth)
can be achieved by Hypoxia-Ischemia (HI). Here we
investigated the neuroprotective effect of EPO in a
model of neonatal HI injury in the P3 rat pup using
DTI, MRS and immunohistochemistry. EPO appears able
to reduce tissue loss and white matter injuries but
it retains compromised metabolism consistent with
incomplete recovery from EPO, giving a highly
relevant new insight in the neuroprotective effect
of EPO. |
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16:12 |
348. |
Neurochemical Profile of the
Mouse Hypothalamus Using 1H MRS at 14.1T |
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Hongxia Lei1,2,
Carole Poitry-Yamate1, Frederic Preitner3,
Bernard Thorens3, Rolf Gruetter1,4
1Ecole Polytechnique Federale de Lausanne,
Lausanne, Vaud, Switzerland; 2Radiology,
University of Lausanne , Lausanne, Vaud,
Switzerland; 3Institute of Physiology,
University of Lausanne , Lasuanne, Vaud,
Switzerland; 4Radiology, University of
Geneva, Geneva, Switzerland |
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MRS of hypothalamus in
mice is very challenging due to its small volume and
deep structure. In present study, we examine the
feasibilities of 1H MRS of the
hypothalamus in GLUT8 knockout mice at 14.1T. The
quality spectra resulted in nearly 20 metabolites,
so called the neurochemical profile of the mouse
hypothalamus. |
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16:24 |
349. |
1H MRS of the Visual Cortex
Under Chronic Ocular Hypertension |
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Kevin C. Chan1,2,
Kwok-fai So3, Ed X. Wu1,2
1Laboratory of Biomedical Imaging and Signal
Processing, The University of Hong Kong, Hong Kong
SAR, China; 2Department of Electrical and
Electronic Engineering, The University of Hong Kong,
Hong Kong SAR, China; 3Department of
Anatomy, The University of Hong Kong, Hong Kong SAR,
China |
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This study aims to
employ in vivo 1H MRS to monitor the
metabolic changes in the visual cortex in an
experimental model of chronic glaucoma. Five
Sprague-Dawley rats were prepared to induce ocular
hypertension unilaterally in the right eye by
photocoagulating the episcleral and limbal veins
using an argon laser. 1H MRS was performed to each
side of the visual cortex 6 weeks after laser
treatment. The results of this study suggest that
glaucoma is associated with alterations in the
metabolism of choline-containing compounds in the
normally-appearing visual cortex. Measurement of the
Cho:Cr reduction in the visual cortex may be a
noninvasive biomarker for the disease. |
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16:36 |
350. |
Proton MRS Investigation of
Human Glioma Models in Nude Mice at 14.1 T |
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Vladimir Mlynarik1,
Cristina Cudalbu1, Virginie Clément2,
Denis Marino2, Ivan Radovanovic2,
Rolf Gruetter1,3
1Laboratory of Functional and Metabolic
Imaging, Ecole Polytechnique Fédérale de Lausanne,
Lausanne, Switzerland; 2Dept. of Genetic
Medicine and Development, University of Geneva
School of Medicine, Geneva, Switzerland; 3Departments
of Radiology, Universities of Lausanne and Geneva |
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Injecting separated
fresh or cultured human glioma-initiating cells into
brain of nude mice produced tumors having two
different phenotypes. The tumors from cultured cells
grew fast and showed necrosis and Gd enhancement,
while the gliomas from fresh cells grew slowly and
showed no necrosis and very little Gd enhancement.
Proton localized spectroscopy at 14.1 Tesla revealed
different metabolic profiles in the two types of
tumors. Characteristic changes of metabolite
concentrations were observed in the brain tissue
near the injection site of the cultured glioma-initiating
cells before solid tumors were detected by MRI. |
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16:48 |
351. |
Redox Dependence and
Compartmentation of [13C]Pyruvate in the
Brain of Deuterated Rats Bearing Implanted C6
Gliomas |
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Tiago Brandao
Rodrigues1, Pilar Lopez-Larrubia1,
Sebastián Cerdán1
1LISMAR, Instituto de Investigaciones
Biomédicas CSIC, Madrid, Spain |
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We investigated the
redox dependence and compartmentation of the
pyruvate pool in the brain of partially deuterated
rats bearing C6 gliomas. The rats were infused with
[1-13C]glucose and [2-13C]pyruvate
or [U-13C3]lactate. The
relative amounts of [3-13C]lactate
derived from glucose to the [2-13C] or
[U-13C3]lactate isotopomers
derived from monocarboxylates decreased in the order
contralateral>ipsilateral>tumor regions, revealing a
progressive reduction in glycolysis for regions
containing increasing endogenous lactate
concentrations. Deuterated animals bearing C6
tumors, infused with [1-13C]glucose and
[2-13C]pyruvate, showed different
deuterium enrichments in the methyl groups of
cerebral [3-13C] and [2-13C]lactate,
revealing a slow mixing of the [3-13C]
and [2-13C]pyruvate precursors in the
2H exchange timescale of their methyl
groups. |
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17:00 |
352. |
In Situ 3D MR Metabolic
Imaging of Microwave-Irradiated Rodent Brain: A New
Tool for Metabolomics Research |
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Robin A. de Graaf1,
Golam MI Chowdhury1, Peter B. Brown1,
Douglas L. Rothman1, Kevin L. Behar1
1MRRC, Yale University, New Haven, CT, USA |
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High-resolution and
high-sensitivity MR imaging and spectroscopy on
microwave-irradiated rat brain is demonstrated.
Structural integrity and metabolic stability are
confirmed for at least 12 hours through the use of
DTI and T2-weighted MRI and 1H MRS. 1H MR spectra of
microwave-irradiated rat brain are indistinguishable
from in vivo 1H MR spectra. When combined
with in vivo infusion of 13C-labeled
compounds, the in situ 1H MRSI data allows the
detection of metabolic fluxes at high spatial
resolution. |
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17:12 |
353. |
Quantification of Brain Glycogen Concentration and
Turnover Through Localized 13C NMR of
Both the C1 and C6 Resonance |
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Ruud Bernardus van
Heeswijk1, Florence D. Morgenthaler1,
Lijing Xin1, Rolf Gruetter1,2
1Center for BioMedical Imaging (CIBM), Ecole
Polytechnique Fédérale de Lausanne (EPFL), Lausanne,
VD, Switzerland; 2Departments of
Radiology, Universities of Lausanne and Geneva,
Lausanne and Geneva, Switzerland |
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Brain glycogen
concentration and turnover were determined in
vivo in the rat by simultaneously monitoring
both the C1 and C6 resonances with 13C
NMR. These resonances lie 3.9 kHz apart at 9.4 T, so
to prevent a chemical shift displacement artifact a
sequence based on the Fourier series window was
implemented. After bringing the C1 resonance in
steady state through 'pre-labeling' with 1-13C1
glucose, an acute infusion of 1,6-13C2
glucose was used to label the C6 resonance of
glycogen and so estimate its turnover time, while
the C1 resonance was used to monitor for
concentration changes. |
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17:24 |
354. |
17O T1/T2*
Tissue-Relaxation Rates with Anatomical Contrast in
the Rat Brain at 16.4 T |
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Hannes M. Wiesner1,
David Z. Balla1, Rolf Pohmann1,
Wei Chen2, Kamil Ugurbil2,
Kamil Uludag1
1High-Field Magnetic Resonance Center, Max
Planck Institute for Biological Cybernetics,
Tübingen, Germany; 2Radiology, Center for
Magnetic Resonance Research, University of Minnesota
Medical School, Minneapolis, MN, USA |
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The direct NMR detection
of 17O benefits particularly from higher
field strengths and is a promising tool in the study
of cerebral oxygen metabolism. The aim of this study
was to acquire anatomical MRS images of H217O
at natural abundance concentration in the rat head
at 16.4 Tesla. Intra-cortical contrast and
differences in tissue-specific relaxation of brain
and muscle tissue were found, enabling optimizations
in contrast and sensitivity. Based on these results
implications on the spatial specificity of oxygen
consumption (CMRO2) measurements using
17O2-enriched gas will be
discussed. |
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17:36 |
355. |
Effect of Short- And Long-Term
Type 1 Diabetes on the Neurochemical Profile in STZ-Induced
Diabetic Rats at 9.4 T |
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Wen-Tung Wang1,
Sang-Pil Lee2,3, Irina Smirnova4,
In-Young Choi1,5
1Hoglund Brain Imaging Center, University of
Kansas Medical Center, Kansas City, KS, USA; 21Hoglund
Brain Imaging Center, University of Kansas Medical
Center, Kansas City, KS, USA; 32Department
of Molecular & Integrative Physiology, University of
Kansas Medical Center, Kansas City, KS, USA; 4Department
of Physical Therapy and Rehabilitation Sciences,
University of Kansas Medical Center, Kansas City,
KS, USA; 52Department of Neurology,
Molecular & Integrative Physiology, University of
Kansas Medical Center, Kansas City, KS, USA |
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The neurological
consequences of diabetes mellitus were assessed
during short- and long-term streptozotocin-induced
diabetes in the rat brain. Early yet subtle changes
of neurochemical contents in the streptozotocin(STZ)-induced
diabetes were detected using in vivo
ultra-short echo time 1H MRS at 9.4 T. Acute
hyperglycemia led to significant changes in alanine,
ß-hydroxybutyrate, glutamine, myo-inositol, lactate,
taurine, and choline compounds (GPC+PCho). While
glutamine showed a transient increase during the
short-term hyperglycemic period, others maintained
persistent changes through the chronic stage. Four
weeks after the STZ-injection, aspartate,
glutathione and N-acetylaspartate started to show
significant decreases, indicating increased
oxidative stress and neuronal loss during the
disease progression. |
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17:48 |
356. |
Dynamic Metabolic Modeling of
[2-13C]Acetate Metabolism in the Rat Brain |
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Alexander A. Shestov1,
Dinesh K. Deelchand1, Pierre-Gilles Henry1
1Radiology, University of Minnesota Medical
School, Minneapolis, MN, USA |
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Carbon-13 MRS combined
with metabolic modeling allows measurement of
metabolic rates in vivo. Most 13C metabolic
modeling studies have been performed using
13C-glucose as the infused substrate. Acetate, a
glial-specific substrate, is an attractive
alternative to glucose for the study of neuronal-glial
interactions. Here we report kinetic parameters for
acetate transport and utilization, as well as
dynamic metabolic modeling of glutamate and
glutamine 13C turnover curves obtained during
13C-acetate infusion with a two-compartment
neuronal-glial model. |
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