| Animals in White Matter Diseases |
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Friday 24 April 2009 |
| Room 311 |
10:30-12:30 |
Moderators: |
Charles R.G. Guttmann and Victor Song |
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10:30 |
832. |
Deep Gray Matter T2
Hypointensity Correlates with Disability in a Murine
Model of MS |
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Istvan Pirko1,
Aaron J. Johnson2, Anne K. Lohrey2,
Jun Ying3, Diana Lindquist4,
R. Scott Dunn4
1Department of Neurology, University of
Cincinnati, Cincinnati, OH, USA; 2Department
of Neurology, University of Cincinnati, USA; 3Department
of Biostatistics and Epidemiology, University of
Cincinnati, USA; 4Imaging Research
Center, Cincinnati Childrens Hospital Medical
Center, Cincinnati, OH, USA |
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Advanced MRI studies
have demonstrated a variety of non-lesional
pathology in MS. T2 weighted scans of deep gray
matter nuclei often reveal hypointensity, which has
been shown to correlate with cognitive,
neuropsychiatric and motor dysfunction. In this
abstract we demonstrate the first MS model of deep
gray matter T2 hypointensity. In a TMEV induced MS
model in SJL/J mice, gradual development of thalamic
T2 hypointensity was observed. Quantitative
intensity analysis demonstrated a strong correlation
between the degree of hypointensity and disability.
This novel model will allow us to study the
pathogenesis and significance of deep gray T2
hypointensity in MS. |
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10:42 |
833. |
T2 Relaxation Parallels
Progressive Clinical Symptoms of Demyelination in a
Novel Transgenic Mouse Model |
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Thomas Mueggler1,
Hartmut Pohl2, Dieter Riethmacher3,
Christof Baltes1, Ueli Suter2,
Markus Rudin1,4
1Institute for Biomedical Engineering,
University and ETH Zurich, Zurich, Switzerland;
2Institute for Cell Biology, ETH Zurich,
Zurich, Switzerland; 3Human Genetics
Division, Southampton University School of Medicine,
Southampton, UK; 4Institute of
Pharmacology and Toxicology, University of Zurich,
Zurich, Switzerland |
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A novel mouse model of
demyelination uses intrinsic triggering of
oligodendrocyte cell death leading to progressive
symptoms allowing to disentangle the role of
apoptotic cell death from that of the immune system
in Multiple Sclerosis. To evaluate the sensitivity
of various MR readouts for monitoring the pathology
we assessed T2, MTR and infiltration of macrophages
in diseased and control mice. Whereas T2
hyper-intensities become apparent at a time-point of
first clinical symptoms a MTR decrease is only
present at progressed pathology stage. No
infiltration of macrophages could be measured
reflecting integrity of BBB and weak recruitment of
blood-borne immune cells. |
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10:54 |
834. |
Neural Precursor Migration
Following Intracerebroventricular Delivery During
the Chronic Phase of Experimental Allergic
Encephalomyelitis Is Reduced as Compared to the
Acute Phase |
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Naser Muja1,2,
Mikhal Cohen3, Jiangyang Zhang1,
Assaf A. Gilad1,2, Piotr Walczak1,2,
Tamir Ben-Hur3, Jeff W.M. Bulte1,2
1Radiology, Divivsion of MR Research, Johns
Hopkins University, Baltimore, MD, USA; 2Institute
for Cell Engineering, Johns Hopkins University,
Baltimore , MD, USA; 3Department of
Neurology, Hadassah-Hebrew University Medical
Center, Jerusalem, Israel |
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Using experimental
autoimmune encephalomyelitis (EAE) as a mouse model
for multiple sclerosis, we used serial MR imaging of
Feridex-labeled neural precursor cells (NPCs) to
detect potential differences in the migratory
response of ICV-transplanted NPCs between the acute
inflammatory or the chronic demyelinated phase of
the disease. We found that cell movements are
determined by the phase of EAE, with a
characteristic radial migration pattern of cells
moving out from the ventricular spaces into and
around blood vessels within the somatosensory cortex
during the acute but not the chronic phase. |
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11:06 |
835. |
MRI Estimation of Sub-Clinical
Disease in Japanese Macaque Encephalomyelitis |
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William D. Rooney1,
Steven G. Kohama, Paul Wang, Jeffrey M. Njus, Scott
W. Wong, Lawrence S. Sherman, Michael K. Axthelm,
Gail H. Marracci, Dennis N. Bourdette
1Advanded Imaging Research Center, Oregon
Health and Science University, Portland, OR, USA |
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A spontaneously
occurring demyelinating disease has recently been
characterized in Japanese macaques (Macaca fuscata)
at the Oregon National Regional Primate Center (ONPRC);
the disease has been named "Japanese macaque
encephalomyelitis" (JME). JME bears many
similarities to human multiple sclerosis (MS) but
has a much greater incidence. Typically, JME has an
acute onset with rapid progression and is readily
detected in affected individuals as impaired
ambulation or motor skills during routine
observation. The major finding of this study
suggests that JME occurs with an even higher
incidence that previously appreciated and with a
disease severity that ranges from benign to
fulminant. These observations have important
implications for the development of a non-human
primate model of MS based on a naturally occurring
disease. |
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11:18 |
836. |
Q-Space and Conventional DWI
of Axonal and Myelin Damage in the Rat Spinal Cord
After Axotomy |
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Jonathan Andrew David
Farrell1,2, Jiangyang Zhang2,
Melina Jones3, Cynthia A. DeBoy3,
Paul N. Hoffman3,4, Seth A. Smith1,2,
Daniel S. Reich3,5, Peter A. Calabresi3,
Peter C. van Zijl1,2
1F.M. Kirby Research Center for Functional
Brain Imaging, Kennedy Krieger Institute, Baltimore,
MD, USA; 2Neuroscience Section, Division
of MR Research, Dept. of Radiology, Johns Hopkins
University School of Medicine, Baltimore, MD, USA;
3Dept. of Neurology, Johns Hopkins
University School of Medicine, Baltimore, MD, USA;
4Dept. of Ophthalmology, Johns Hopkins
University School of Medicine, Baltimore, MD, USA;
5Division of Neuroradiology, Dept. of
Radiology, Johns Hopkins University School of
Medicine, Baltimore, MD, USA |
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Dorsal root axotomy
causes axonal degeneration with subsequent delayed
myelin damage in the dorsal column. We investigated
water diffusion perpendicular and parallel to the
rat spinal cord (3 and 30 days post-injury). We
compared contrasts from q-space analysis to
conventional anisotropy and diffusivity measurements
and histological staining for axonal and myelin
damage. Perpendicular diffusion was increased, and
more Gaussian in lesions compared to contralateral
white matter, but was not specific for myelin
damage. Parallel diffusion was decreased, and less
Gaussian, which may be specific for axonal damage.
Q-space contrasts, including kurtosis excess,
provide a comprehensive assessment of white matter
damage. |
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11:30 |
837. |
Diffusion Anisotropy
Correlates Compound Action Potential in the Optic
Nerve from Mice of Retina Ischemia |
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Qing Wang1,
Roman Vlkolinsky2, Sheng-Kwei Song3,
Andre Obenaus4
1Washington University, Saint Louis, MO, USA;
2Loma Linda University School of
Medicine; 3Washington University School
of Medicine; 4Loma Linda Unieristy School
of Medicine, Loma Linda, CA, USA |
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The compound action
potential (CAP) amplitude was measured by the
extracellular recording ex vivo on optic nerves from
the control, and retinal ischemia mice at 3 and 7
days after injury. The axonal and myelin integrity
of optic nerve from control and retinal ischemic
mice as evaluated using diffusion tensor imaging
(DTI). The correlation between DTI and CAP was
established. The results suggest that the decreased
diffusion anisotropy may reflect the function of
optic nerve after retinal ischemia better despite
the presence of axonal injury may be responsible for
the long term disability of visual function. And the
overall functional assessment would be best to be
evaluated by diffusion anisotropy than axial or
radial diffusivity alone. |
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11:42 |
838. |
White Matter Changes in a
Model of Temporal Lobe Epileptogenesis: A Combined
Diffusion Tensor Imaging and Histopathology Study |
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Willem Maarten Otte1,2,
Pieter van Eijsden1, W. S. van der Hel1,
O. van Nieuwenhuizen1, Rick M. Dijkhuizen2,
R A. de Graaf3, Kees P.J. Braun1
1Rudolf Magnus Institute of Neuroscience, UMC
Utrecht, Utrecht, Netherlands; 2Image
Sciences Institute, UMC Utrecht, Utrecht,
Netherlands; 3Department of Diagnostic
Radiology, Magnetic Resonance Research Center, Yale
School of Medicine, New Haven, CT, USA |
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Although epilepsy is
considered to be a grey matter disease, diffusion
tensor imaging (DTI) studies have demonstrated that
white matter is affected. However, interpretation of
DTI findings is often complicated by the lack of
histology. We characterized white matter changes
longitudinally during epileptogenesis using DTI and
histology in a rat model of temporal lobe epilepsy (TLE).
Our analysis demonstrated significant reduction in
Lambda1 of the corpus callosum at four weeks, before
spontaneous seizures occur. Histology confirmed that
myelin was affected at four weeks, but normalizes.
Axonal integrity was not affected. Diffusion
properties behave different during epipileptogenesis
than in TLE. |
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11:54 |
839. |
Long-Term Treatment with
Antipsychotics Affects NAA T1 in Normal Rat Brain |
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Diana M. Lindquist1,
R S. Dunn1
1Radiology, Cincinnati Children's Hospital
Medical Center, Cincinnati, OH, USA |
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Multiple MRS studies
have been reported comparing schizophrenic patients
and normal subjects, with mixed results. Differences
between normal subjects and patients may be due to
changes in either water or metabolite relaxation
times. Changes in relaxation times could result from
the disease and/or the drugs used to treat it. In
this 6-month study, we found that NAA T1 times in
normal rat brain are significantly shorter for rats
treated with either haloperidol or clozapine. Long
term treatment with antipsychotics appears to
decrease NAA T1 values, which may result in an
overestimation of the NAA concentration in treated
schizophrenic patients. |
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12:06 |
840. |
Imaging Model of
Antidepressant Effects: A Pre-Clinical Investigation
Using Pharmacological Magnetic Resonance Imaging |
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Sakthivel Sekar1,
Marleen Verhoye2, Johan Van Audekerke2,
Greetje Vanhoutte2, Andrew M. Blamire3,
Thomas Steckler4, Mohammed Shoaib1,
Annemie Van der Linden2
1Psychobiology Research Group, Newcastle
University, Newcastle upon Tyne, Tyne and Wear, UK;
2Bio-Imaging Lab, University of Antwerp,
Antwerp, Belgium; 3Newcastle Magnetic
Resonance Centre, Newcastle University, Newcastle
upon Tyne, UK; 4Johnson & Johnson
Pharmaceutical Research & Development, Beerse,
Belgium |
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Pharmacological MRI (phMRI)
is a rapidly developing non-invasive advancement of
functional Magnetic Resonance Imaging (fMRI) - phMRI
signatures (neuroactivity maps) can be utilized to
investigate the effects of psychotropic compound’s
activity, thus serving as surrogate markers to
screen for novel therapeutics. The study aims to map
the key regions susceptible to acute and chronic
exposure of the novel antidepressants: citalopram,
reboxetine & bupropion in rodents there by to
pharmacologically characterize the mechanisms
underlying their clinical efficacy, using phMRI.
This approach has also been extended to investigate
the specific-receptor involvement by combining
antidepressant with a highly receptor-selective
antagonist, to obtain deeper insight felicitating
translational research activities, to & from the
clinic. |
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12:18 |
841. |
Pathological Correlates of the
Decreased Axial Diffusivity in White Matter Injury |
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Mingqiang Xie1,
Matthew D. Budde2, Chin-I Chen2,
Kathryn Trinkaus3, Regina C. Armstrong4,
Anne H. Cross5, Sheng-Kwei Song2
1Radiology, Washington University, St. Louis
, MO, USA; 2Radiology, Washington
University, St. Louis, MO, USA; 3Biostatistics,
Washington University, St. Louis, MO; 4Anatomy,
Physiology, and Genetics, Uniformed Services
University of the Health Sciences, Bethesda, MD,
USA; 5Neurology and Neurosurgery,
Washington University, St. Louis, MO, USA |
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Decreased axial
diffusivity from DTI has recently been used as a
noninvasive biomarker for detecting axonal injury.
The current study compared axial diffusivity with
histology of YFP mouse corpus callosum (CC)
throughout cuprizone-induced demyelination.
Decreased axial diffusivity, axonal injury and
increased microglia/macrophages at 4 weeks of
cuprizone ingestion, and then they returned to the
control level at 10 weeks of continuous treatment.
In contrast, astrogliosis increased at 4 weeks and
further increased at 10 weeks. The results
demonstrate that decreased axial diffusivity mirrors
the reversible nature of axonal injury and microglia/macrophage
infiltration in cuprizone-treated mouse CC, and is
not related to astrogliosis. |
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