Animal Models of Brain Disease
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Monday 7 May 2012
Room 201  10:45 - 12:45 Moderators: Eric T. Ahrens, Shella D. Keilholz

10:45 0016.   Measurement of Metabolite concentration changes in the rat barrel cortex during sustained trigeminal stimulation
Nathalie Just1, and Rolf Gruetter1,2
1LIFMET, CIBM/EPFL, Lausanne, Switzerland, 2Department of Radiology, Universities of Lausanne and Geneva, Switzerland

Oxidative metabolism is considered to be the primary mechanism to fulfill the brain’s energetic demands both at rest and during activation. In the present work, functional MR spectroscopy was performed in a rat model during prolonged stimulation and rest. Timecourses of metabolite concentrations demonstrated significant positive changes for [Lactate] and [Glutamate] during sustained barrel cortex activation relative to rest while [Glucose] and [Aspartate] diminished in line with previous studies in humans. For the first time, the dynamics of metabolite concentration during sustained somatosensory activation in the rats using fMRS were evaluated.

10:57 0017.   Mapping the living mouse brain neural architecture: strain specific patterns of the brain connectional anatomy
Laura-Adela Harsan1, Marco Reisert1, Annette Merkle1, Jürgen Hennig1, and Dominik von Elverfeldt1
1Medical Physics, Department of Radiology, University Medical Center, Freiburg, Germany

In the present study we probe at microscopic level, the ensemble of anatomical neurocircuity of the living mouse brain, using diffusion fiber tracking, comparatively in BALB/cJ and C57Bl6/N mice. Exquisite brain anatomical details of the mouse brain neural architecture were revealed by combining the use of Cryoprobe technology for MRI data acquisition and a new global fiber tracking algorithm for post-processing. We depicted inter- and intra-strain variations in the general wiring scheme of the mouse brain. As a prominent feature, BALB/cJ mice show great within-strain variations in the callosal interhemispheric connectivity.

11:09 0018.   
Alterations in brain development induced by whole-brain irradiation in young mice
Lisa M Gazdzinski1, Kyle Cormier1, C Shun Wong2,3, Jason P Lerch1, and Brian J Nieman1
1Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada, 2Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada, 3Radiation Oncology, University of Toronto, Toronto, Ontario, Canada

Cranial radiotherapy for the treatment of childhood cancer has been implicated in the development of progressive neurocognitive dysfunction, but the mechanism remains poorly understood. Using longitudinal in vivo MRI, this study identified regions of the developing mouse brain most sensitive to irradiation at a young age. Irradiation led to bilateral decreases in growth rate and volume in both white and gray matter regions. The time course varied among brain structures and apparent recovery was observed in a subset of structures. The systematic approach used in this work will serve as a valuable tool for investigating neuroprotective strategies to mitigate neurocognitive late effects.

11:21 0019.   
Evidence of the myelin origin of the short T2* component in white matter: a combined magnetization transfer and T2* relaxometry experiment in the marmoset brain at 7T
Pascal Sati1, Peter Van Gelderen2, Afonso C Silva3, Hellmut Merkle4, Daniel S Reich1, and Jeff H Duyn2
1Translational Neuroradiology Unit, Neuroimmunology Branch, NINDS, NIH, Bethesda, Maryland, United States, 2Advanced MRI Section, Laboratory of Functional and Molecular Imaging, NINDS, NIH, Bethesda, Maryland, United States, 3Cerebral Microcirculation Unit, Laboratory of Functional and Molecular Imaging, NINDS, NIH, Bethesda, Maryland, United States, 4Laboratory of Functional and Molecular Imaging, NINDS, NIH, Bethesda, Maryland, United States

Recent gradient-echo studies suggest a multi-component T2* decay in white matter (WM) fibers of human brain with the existence of a short component (few ms) tentatively attributed to water protons trapped inside myelin. In this study, we performed a combined magnetization transfer and T2* relaxometry experiment at 7T in marmoset brain. We found that short T2* component in WM experienced an MT effect with a dependence on the delay time between MT pulse and multi-gradient echo acquisition that is distinctly different from that of other water compartments, reflecting the restricted exchange probably occurring between the various water pools in WM.

11:33 0020.   
In vivo Hydrogen-1, Sodium-23, Phosphorus-31, and Potassium-39 Magnetic Resonance Imaging after Middle Cerebral Artery Occlusion permission withheld
Friedrich Wetterling1, Nagesh Shanbhag2, Lothar Schilling2, Stefan Kirsch1, and Lothar Rudi Schad1
1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany, 2Division of Neurosurgical Reasearch, Heidelberg University, Mannheim, Germany

In the current feasibility study, four single-tuned surface resonators for Hydrogen-1 (1H), Sodium-23 (23Na), Phosphorus-31 (31P), and Potassium-39 (39K) MRI were used in conjunction with a linearly-polarized 1H-volume resonator to examine in vivo brain tissue after induction of focal ischaemia. The 1H-Apparent diffusion coefficient, as well as the relaxation time weighted 1H-, 23Na-, 31P, and 39K-signals were analysed and expressed as a percentage change compared to contralateral normal tissue. We conclude that multi-parameter X-nuclei MRI at 9.4T provides a promising tool to study metabolic and ion concentration changes after cerebral artery occlusion non-invasively with sufficient spatial and temporal resolution.

11:45 0021.   
Longitudinal MRI assessment of brain microstructural changes induced by chronic Toxoplasma gondii infection in mice
Alexandru Parlog1,2, Marco Reisert1, Dominik von Elverfeldt1, Ildiko Dunay2, and Laura-Adela Harsan1
1Department of Radiology, University Medical Center, Freiburg, Germany, 2Institute for Medical Microbiology, Uniklinik Magdeburg, Magdeburg, Germany

In the present study we provide longitudinal insight into the pathological effects of the T. gondii infection on the mouse brain microstructure. We explore the use of DT-MRI and fiber tracking to investigate the impact of the T. gondii infection on the whole brain connectivity pattern, in the living mouse. MR images illustrate the presence of lesions in key brain structures leading to impaired structural connectivity between important areas of the somatosensory and limbic systems. These modifications might explain the sensorimotor deficits observed in the infected mice.

11:57 0022.   Hyperpolarized 13C Ascorbates in the Anesthetized Rat Brain
David M. Wilson1, John Kurhanewicz1, and Kayvan R. Keshari1
1Radiology and Biomedical Imaging, University of California, San Francisco (UCSF), San Francisco, CA, United States

The reducing agents glutathione and Vitamin C are maintained at high concentrations in the brain, and have a critical role in dealing with reactive oxygen species seen as culprits in aging, neurodegenerative disease, and ischemic injury. We have developed [1-13C] dehydroascorbate, the oxidized form of Vitamin C, as a redox sensor for in vivo imaging using hyperpolarized 13C spectroscopy. In anesthetized rats, hyperpolarized [1-13C] DHA was rapidly converted to [1-13C] Vitamin C within the brain. In contrast, hyperpolarized [1-13C] Vitamin C studies demonstrated no observable oxidation to [1-13C] DHA, with diminished signals in brain voxels consistent with limited blood-brain-barrier penetration.

12:09 0023.   19F/1H MRI of Brain Inflammation in Experimental Autoimmune Encephalomyelitis
Helmar Waiczies1,2, Stefano Lepore1,2, Jason M Millward3,4, Bettina Purfürst5, Thoralf Niendorf2,3, and Sonia Waiczies1,2
1Ultrahigh Field Imaging in Neuroinflammation, Experimental and Clinical Research Center (ECRC), a cooperation of the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine, Berlin, Deutschland, Germany, 2Berlin Ultrahigh Field Facility (B.U.F.F.), Max-Delbrueck-Center for Molecular Medicine, Berlin, Deutschland, Germany, 3Experimental and Clinical Research Center (ECRC), Charité University Medicine Campus Berlin Buch, Berlin, Deutschland, Germany, 4Experimental Neuroimmunology, Charité Universitätsmedizin Berlin, Berlin, Germany, 5Electron Microscopy, Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany

In the present study we employed an animal model of MS, the Experimental Autoimmune Encephalomyelitis (EAE) to explore the in vivo uptake of fluorine (19F) nanoparticles by inflammatory cells during encephalomyleitis. Using a 32-leg 1H/19F birdcage coil dedicated for mouse head imaging, we detected and quantified19F nanoparticles (containing perfluoro-15-crown-5-ether) taken up and transported by macrophages within the cerebellum following intravenous application. The application of 19F nanoparticles for imaging immune cells in conditions such as encephalomyelitis is an emerging field that will be ideal to study the kinetics of immune cell localization during the development of inflammation.

12:21 0024.   Reduction of Brain Virus by minocycline and combination anti-retroviral therapy produces neuronal protection in a primate model of AIDS
Eva-Maria Ratai1,2, Robert J Fell1, Julian He1,2, Michael Piatak3, Jeffrey D Lifson3, Tricia H Burdo4, Jennifer Campbell4, Patrick Autissier4, Lakshmanan Annamalai5, Eliezer Masliah6, Susan V Westmoreland2,5, Kenneth C Williams4, and R Gilberto González1,2
1Neuroradiology Division, Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, 2Harvard Medical School, 3SAIC Frederick, Inc., Frederick, MD, United States, 4Biology Department, Boston College, Chestnut Hill, MA, United States,5Department of Pathology, New England Primate Research Center, Southborough, MA, United States, 6Department of Neurosciences, University of California at San Diego, La Jolla, CA, United States

MR spectroscopy was used to investigate the neuropathogenesis of HIV-Associated Neurocognitive Disorders (HAND). Twenty-three simian immunodeficiency virus-infected, CD8- T-lymphocyte depleted rhesus macaques were studied. Antiretroviral therapy and minocycline were used to modulate their disease progression. Both treatments resulted in the decrease of viral RNA in the brain. Severity of neuronal damage measured by NAA/Cr was shown to be dependent on CNS viral levels. The degree of CNS viral infection was directly influenced by plasma viral load and infected/activated monocytes that traffic virus into the brain. These findings suggest monocyte-directed therapies for a future direction of HAND treatment.

12:33 0025.   Characterization of Cerebrovascular Parameters using MRI in eNOS and sGClower case Greek alpha1 Knockout Mice
Ji-Yeon Suh1, Shunning Huang1, Dmitriy N. Atochin2, Paul L. Huang2, Emmanuel S Buys3, Peter Brouckaert4, Jeong Kon Kim1,5, Woo Hyun Shim1, Seon Joo Kwon1, and Young Ro Kim1
1Athinoula A, Martinos Center for Biomedical Imaging, Massachusettes General Hospital, Charlestown, MA, United States, 2Cardiology, MGH, Boston, MA, United States, 3Anesthesia, Massachusetts General Hospital, Boston, MA, United States, 4VIB Department of Melecular Biomedical Research, Ghent University, Ghent, Belgium, 5Asan Medical Center, University of Ulsan, Seoul, Korea, Republic of

Although constitutively produced eNOS and sGC are necessary enzymes for maintaining a normal endothelial function, cerebrovascular characters in the mouse brain lacking these enzymes have not been investigated. We aimed to characterize MRI-derived vascular parameters in eNOS and sGC knockout mice. Our results show an increased water exchange index (WEI) and a lower aquaporine expression in knockout mice, which imply the inherently weakened BBB function precluding the increased channel-mediated water exchange, This work provides a basis for elucidating the pathophysiological relationship between NO synthase and the BBB integrity, and its involvement with ischemic damage.