ISMRM 21st Annual Meeting & Exhibition 20-26 April 2013 Salt Lake City, Utah, USA

Animal Models 2

Tuesday 23 April 2013

Room 155 EF  16:00 - 18:00 Moderators: Ichio Aoki, Emmanuel L. Barbier

16:00 0335.   
A Modified Photothrombotic Stroke Model Using Implantable Optic Fiber: In-Bore Stroke Induction for Probing Peri-Infarct Spreading Depolarization
Yu-Chieh Jill Kao1, Hsin-Yi Lai1, Chris Kao1, and Yen-Yu Ian Shih1
1Experimental Neuroimaging Laboraory, Department of Neurology and Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, Chapel Hill, NC, United States, Chapel Hill, NC, United States

A photothrombotic stroke model using implantable optic fiber (IOF photothrombosis) was proposed in rats to visualize ADC and CBF changes before, during and after stroke onset. Peri-infarct spreading depolarization (PID) and post-PID oligemia were demonstrated for the first time by high resolution diffusion/perfusion MRI. IOF photothrombosis is highly feasible to create ischemic lesion in predetermined brain area with well-controlled infarct size, which opens up new avenues for preclinical stroke research.

16:12 0336.   in vivo Assessments of Ocular Dynamics, Axonal Transport and Microstructural Integrity in the Visual System Upon Neonatal Hypoxic-Ischemic Injury
Kevin C. Chan1,2, Swarupa Kancherla3, and Ed X. Wu4
1Neuroimaging Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, 2Departments of Ophthalmology and Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, 3Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, 4Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong, China

This study employed dynamic gadolinium-enhanced MRI, manganese-enhanced MRI and diffusion tensor imaging to evaluate the ocular dynamics, axonal transport and microstructural integrity in the visual system of adult rats that underwent neonatal unilateral hypoxic-ischemic injury. Dynamic Gd-enhanced MRI showed leakage of the Gd contrast into the vitreous humor from the anterior chamber in the ipsilesional eye but not the contralesional eye after systemic administration of Gd. Manganese-enhanced MRI showed reduced anterograde axonal transport of Mn2+ ions along the visual pathway projected from the ipsilesional eye compared to contralesional eye upon bilateral Mn2+ intravitreal injection. In addition, the superior colliculus ipsilateral to the injured hemisphere appeared to be displaced across the midline to the contralateral hemisphere. Diffusion tensor imaging showed disorganization of the ipsilesional optic nerve compared to the contralesional optic nerve. The results of this study provided important evidence for understanding the chronic pathophysiological changes in the visual system after neonatal unilateral hypoxic-ischemic injury.

16:24 0337.   A Novel Neuroprotective Strategy Using Methylene Blue---A Longitudinal MRI Study
Qiang Shen1, Fang Du1, Shiliang Huang1, Yash Vardhan Tiwari1, and Timothy O. Duong2
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States, 2Research Imaging Institute, UT Health Science Center at San Antonio, San Antonio, Texas, United States

Methylene blue (MB) has unique energy-enhancing and antioxidant properties. It has been recently demonstrated that MB substantially reduces infarct size in transient focal cerebral ischemia in rats by histology. As the next logical step, in this work, we evaluated MB’s neuroprotective effects using non-invasive magnetic resonance imaging (MRI) to longitudinally evaluate ischemic evolution. Comparisons were made with functional changes using neurological assessments. Our results showed that MB significantly reduces infarct size and behavioral deficit in the 60-min transient cerebral ischemia in rats. MB salvaged markedly more initial core and mismatch tissues than vehicle.

16:36 0338.   Rapamycin Treatment Ameliorates Brain Metabolite Levels After Transient Focal Ischemia in Rats
Anjali Chauhan1, Uma R. Sharma2, Naranamangalam R. Jagannathan2, and Y. K. Gupta1
1Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, Delhi, India, 2Department of NMR & MRI Facility, All India Institute of Medical Sciences, New Delhi, Delhi, India

Rapamycin is shown to afford neuroprotection in animal models of neurological disorders. We have previously demonstrated neuroprotective potential of rapamycin in middle cerebral artery occlusion (MCAo) model of stroke. The present study was undertaken to study the biochemical changes after MCAo and also evaluate effect of rapamycin on MCAo injury. We observed increased Lac and decreased Gln/Glu, Cr/PCr, GPC/PC, mI, NAA, Tau and GABA in vehicle group as compared to sham group. In rats treated with rapamycin, decreased Lac and increased Gln/Glu, Cr/PCr, GPC/PC, mI, NAA, Tau and GABA was observed in MCAo rats, suggesting to protective mechanism of rapamycin.

16:48 0339.   Longitudinal Evaluation of White Matter Injury in a Macaque Model of Ischemic Stroke with DTI
Yumei Yan1, Frank Tong2, Chunxia Li1, Stuart Zola1, Leonard Howell1, and Xiaodong Zhang1
1Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States, 2Department of Radiology, Emory University, Atlanta, GA, United States

Stroke induced white matter injury was evaluated in a macaque model of ischemic stroke by using DTI. The fiber tracking and fiber tract-based ROI analysis demonstrated that the white matter tissues in or adjacent to the infarct regions were injured due to the MCA occlusion, as seen in FA and MD and the fiber changes in quantities and their average length. These changes showed similar pattern as that observed in the infarct region, but the scale of the changes was reduced which may be due to the hypoperfusion effect. The results indicate DTI is a robust tool to access the white matter injury in stroke.

17:00 0340.   Effect of Normobaric Hyperoxia (NBO) on Progression of Ischemic Stroke
Yash Vardhan Tiwari1, Fang Du1, Qiang Shen1, and Timothy O. Duong2
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States, 2Research Imaging Institute, UT Health Science Center at San Antonio, San Antonio, Texas, United States

We used quantitative MRI to longitudinally evaluate the effects of normobaric hyperoxia (NBO) treatment on the outcome of ischemic stroke in rats. The major finding is that NBO treatment decreased infarct size by 27.4 % compared to control at day 2. NBO treatment stopped ADC lesion growth at the acute phase, thereby delaying the progression of ischemic penumbra to ischemic core. With reperfusion, substantially more tissue was salvaged compared to controls. The implication of these findings is that NBO can be used to “buy” time and expand the treatment time window in stroke patients

17:12 0341.   MR Elastography in a Murine Stroke Model Reveals Correlation Between Macroscopic Viscoelastic Properties of the Brain and Neuronal Density
Ingolf Sack1, Florian B. Freimann2, Susanne Müller3, Kaspar-Josche Streitberger1, and Juergen Braun4
1Department of Radiology, Charité - Universitätsmedizin Berlin, Berlin, Berlin, Germany, 2Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Berlin, Berlin, Germany, 3Center of Stroke Research, Charité - Universitätsmedizin Berlin, Berlin, Berlin, Germany, 4Institute of Medical Informatics, Charite - University Medicine Berlin, Berlin, Berlin, Germany

Blood flow interruption in a cerebral artery causes brain ischemia with dramatic impact to metabolism and function of the brain. We use MR elastography (MRE) to reveal the alteration of elasticity and viscosity in the murine brain within 28 days after middle cerebral artery occlusion and compared the results to histological markers. MRE-parameters significantly correlated with the number of neurons in both hemispheres and displayed a stroke-related reduction at day 7 after stroke. Our results suggest that neurons contribute to the macroscopic mechanical properties of brain tissue such that a loss of neuronal density reduces the viscoelasticity of brain tissue.

17:24 0342.   
Treatment Efficacy of FTY720 on Experimental Autoimmune Encephalomyelitis Mice Assessed by in vivo Diffusion Basis Spectrum Imaging
Xiaojie Wang1, Yong Wang2, Anne H. Cross3,4, and Sheng-Kwei Song2,4
1Chemistry, Washington University, St. Louis, MO, United States, 2Radiology, Washington University, St. Louis, MO, United States, 3Neurology, Washington University in St. Louis, St. Louis, MO, United States, 4Hope Center of Neurological DIsorders, Washington University, St. Louis, MO, United States

In vivo DBSI was performed on experimental autoimmune encephalomyelitis (EAE) mice undergoing daily treatment with 1 mg/kg FTY720 beginning immediately after immunization. Axon and myelin integrity of optical nerves was assessed using axial and radial diffusivity, respectively, while inflammation extent was evaluated using cellularity and edema water ratio derived by DBSI. Prophylactic treatment with FTY720 prevented optic neuritis in mice induced to develop EAE and preserved optic nerve axons and white matter integrity. The findings suggest that in vivo DBSI may serve as a non-invasive tool to assess the efficacy of disease modifying interventions in EAE and potentially MS.

17:36 0343.   
Microtubule Stabilizer Ameliorates Functional Connectivity in a MAP6 Deficient Mouse: A Manganese Enhanced Magnetic Resonance Imaging Study
Alexia Daoust1,2, Emmanuel Luc Barbier1,2, Annie Andrieux1,2, Sylvain Bohic1,3, and Jean-Chritophe Deloulme1,2
1INSERM U836, grenoble, France, 2Université Joseph Fourier, Grenoble institut des neurosciences, grenoble, France, 3European Synchrotron Radiation Facility, grenoble, France

The STOP/MAP6 null mouse is a microtubule-deficient model of schizophrenia. Using MEMRI, we traced the cortico-thalamic tract after MnCl2 injection in the primary somatosensory cortex. Twenty-four hours after injection, the MRI relative signal intensity revealed that polysynaptic thalamo-cortical and cortico-pontic tracts were affected but not the monosynaptic tracts. These alterations were reversed after administration of a microtubule stabilizer to the animals.

17:48 0344.   Layer-Specific Manganese-Enhanced MRI of Diabetic Rat Retinas Associated with Light and Dark Adaptation at 11.7T
Bryan H. De La Garza1, Charkradhar Velagapudi2, Hanna E. Abboud2, Guang Li1, and Timothy O. Duong3
1Ophthalmology/Radiology, Research Imaging Institute, Univ. of Texas Health Science Center at San Antonio, san antonio, tx, United States, 2Division of Nephrology, Department of Medicine, Univ. of Texas Health Science Center at San Antonio, San Antonio, tx, United States, 3Ophthalmology/Radiology, UT Health Science Center at San Antonio, san antonio, tx, United States

This study used high-resolution manganese-enhanced MRI (MEMRI) to investigate the manganese uptake in different layers of the retina of diabetic retinopathy (DR) rats under light and dark adaptation. In normal rats, dark adaption lowered inner retina MEMRI activity, increased outer retina activity, and did not affect the choroid compared to light adaptation. In DR rats compared to controls, MEMRI revealed significant reduced Mn uptake in all three (inner, outer, and choroid) retinal layers. Differential reduced MEMRI activity in the dark in the outer layer in DR rats compared to control animals, suggesting outer retina dysfunction at early DR.