Animal Models of Brain Disease Other than Stroke
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Friday May 13th
Room 510  10:30 - 12:30 Moderators: Emmanuel L. Barbier and Youssef Wadgihiri

10:30 694.   Neuroanatomical Abnormalities in a Neuroligin3 R451C Knockin Mouse Model of Autism 
Jacob Ellegood1, Jason P Lerch1, and R M Henkelman1
1Mouse Imaging Centre, The Hospital for Sick Children, Toronto, Ontario, Canada

The neuroligin and neurexin genes have been recognized in human autism association studies. The R451C substitution found in human autism has been replicated in a mouse model, the Neuroligin3 R451C knockin (NL3 KI).The purpose of this study was to examine the volumetric and white matter structural changes in the brain of the NL3 KI mouse using high resolution MRI and detailed statistical analysis. The NL3 KI mouse was found to have volume differences in many different structures in the brain. A Corpus callosum decrease is particularly interesting as it is seen in most human studies.

10:42 695.   High-Field (9.4 T) MRI of Brain Dysmyelination by Quantitative Mapping of Magnetic Susceptibility 
Chunlei Liu1,2, Wei Li1, G. Allan Johnson2, and Bing Wu1
1Brain Imaging and Analysis Center, Duke University, Durham, NC, United States, 2Radiology, Duke University, Durham, NC, United States

Myelin sheath wrapping around nerve axons is essential for proper functioning of the central nervous system. Abnormal myelination leads to a wide range of neurological diseases and developmental disorders. We demonstrated that loss of myelin in the shiverer mouse results in a dramatic reduction resulted in a near extinction of susceptibility contrast between gray and white matter. Our data provides new evidences indicating that myelin is the predominant source of susceptibility differences between deep gray and white matter observed in MRI. More importantly, our data suggest that quantitative magnetic susceptibility is a potential endogenous biomarker for myelination.

10:54 696.   In vivo longitudinal 1H MRS study of transgenic mouse models of prion disease in the hippocampus and cerebellum at 14.1T 
Cristina Cudalbu1, Melanie Craveiro1, Vladimir Mlynárik1, Juliane Bremer2, Adriano Aguzzi2, and Rolf Gruetter1,3
1Laboratory for Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, 2Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland, 3Departments of Radiology, Universities of Lausanne and Geneva, Geneva, Switzerland

The prion diseases form a group of fatal neurodegenerative diseases. We performed an in vivo longitudinal 1H MRS study at 14.1T to measure the neurochemical profile of Prnp -/- and PrPÄ32-121 mice in the hippocampus and cerebellum. Our data showed significant increase of Glu, Lac and Ins in the hippocampus of Prnp -/- mice which seems to indicate a dysfunction in the neurotransmitter metabolism and astrogliosis. The decrease of tNAA detected in PrPÄ32-121 mice seems to reflect neuronal loss in while the increase of Ins in the cerebellum may reflect astrogliosis, consistent with the histological features.

11:06 697.   Nanoantioxidants in the treatment of diabetic complications 
Taeko Inoue1, John P Leach1, Daniela Marcano2, Jacob Berlin2, Thomas A Kent3,4, James M Tour2,5, and Robia G Pautler1
1Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, Texas, United States, 2Department of Chemistry, Rice University, Houston, TX, United States,3Department of Neurology, Baylor College of Medicine, Houston, Texas, United States, 4Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, United States, 5Smalley Institute for Nanoscale Science and Technology, Rice University, Houston, TX, United States

Diabetes is associated with vascular complications, which increase the risk of premature death. Oxidative stress plays a key role in development of complications. Therefore, many antioxidant-based therapies have been studied in the hopes of combating complications. They have, however, been largely ineffective perhaps due to low potency or lack of targeting. PEG-HCCs are potent nanoantioxidants which we have tested in a mouse model of diabetes mellitus type 1. We found improvements in cortical blood flow of mice after intravenous treatment with nanoantioxidants. These results indicate that nanoantioxidants may prove effective in treatment of diabetic complications where traditional antioxidants have failed.

11:18 698.   Age-dependent Neurovascular Changes in C57BL/6 Wild Type Mice Using Contrast Enhanced Micro-MR Angiography 
Lindsay K Hill1, Karen C Briley-Saebo2, Dung M Hoang1, Asad Baig1, Brian J Nieman3, Zahi A Fayad2, and Youssef Z Wadghiri1
1Radiology, New York University School of Medicine, New York, NY, United States, 2Radiology, Mount Sinai School of Medicine, New York, NY, United States, 3Mouse Imaging Centre, Hospital for Sick Children, Toronto, Canada

There is increasing evidence that neurovascular dysfunction may be a very important risk factor in the development of Alzheimer’s Disease, an age-related condition. We utilized recently developed Gd-loaded micelles to achieve (100um)3 MR angiograms. Our approach was used to monitor 3D neurovascular changes in individual C57BL/6 wild type mice over one year of normal aging in order to establish a baseline for future research on age-dependent diseases such as Alzheimer’s Disease.

11:30 699.   Proton and phosphorus MRS of a 5xFAD mouse model of Alzheimer's disease 
Vladimir Mlynarik1, Lili Sun-Reimer1, Sharon Janssens1, Matthias Cacquevel2, Hongxia Lei1, Bernard Schneider2, Patrick Aebischer2, and Rolf Gruetter1,3
1Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 2Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 3Departments of Radiology, Universities of Lausanne and Geneva, Switzerland

A new transgenic mouse model of Alzheimer's disease was studied by in vivo by proton and phosphorus MR spectroscopy. This model developed changes in the neurochemical profile, which are characteristic for the human form of this disease (an increase in myo-inositol and a decrease in N-acetylaspartate), as early as in the 40th week of age. In addition, a significant decrease of GABA was observed in the transgenic mice compared with controls. The pseudo-first-order rate constant of the creatine kinase reaction as well as relative concentrations of phosphorus-containing metabolites were not changed significantly in the 36-week old transgenic mice. These results suggest that mitochondrial activity in the 5xFAD mice at this age is sufficient.

11:42 700.   Calcification Imaging with SWIFT in Rat Brain 
Lauri Juhani Lehto1, Alejandra Sierra1, Curtis Andrew Corum2, Djaudat Idiyatullin2, Michael Garwood2, and Olli Heikki Gröhn1
1Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Eastern Finland, Finland, 2Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota, United States

Phase images acquired with gradient echo usually require multiple acquisitions and/or significant post-processing. With SWIFT, phase images can be generated without any post-processing steps. SWIFT preserves off-resonance spin signals up to its full acquisition bandwidth due to the near zero dead time. SWIFT phase imaging was applied to calcification detection formed in epileptic and traumatic brain injury rat brains, ex vivo and in vivo. The calcifications were identified based on their dipole like fields, and due to their diamagnetic susceptibility, have opposite sign than paramagnetic/ferromagnetic objects. Good correspondence between calcification volumes calculated from SWIFT images and histological sections was seen.

11:54 701.   Longitudinal in vivo MRI based spatiotemporal mapping of brain atrophy in the R6/2 mouse model of Huntington's disease 
Manisha Aggarwal1, Susumu Mori1, Michael I Miller2, Wenzhen Duan3, and Jiangyang Zhang1
1Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2Center for Imaging Science, Johns Hopkins University, Baltimore, MD, United States, 3Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Huntington's disease (HD) is a fatal neurodegenerative disorder characterized by progressive brain atrophy. Longitudinal studies in mouse models of HD are therefore important to understand the spatiotemporal progression of brain atrophy in order to identify windows for therapeutic intervention. In this study, longitudinal analysis of deformation based morphometry (DBM) metrics is used to analyze three dimensional in vivo MR images of the R6/2 model of HD from 3 to 12 weeks of age. Longitudinal analysis of DBM-derived metrics enabled elucidation of the growth patterns of wild-type brain development and the spatiotemporal patterns of progressive atrophy in the R6/2 HD brains.

12:06 702.   Tensor based morphometry on the Tc1 mouse model of Down syndrome highlights previously undetected phenotypes 
Benjamin Sinclair1,2, Jon Cleary2, Marc Modat1, Francesca Norris2,3, Frances Wiseman4, Victor Tybulewicz5, Elizabeth Fisher4, Mark Lythgoe2, and Sebastien Ourselin1
1Centre for Medical Image Computing, UCL, London, United Kingdom, 2Centre for Advanced Biomedical Imaging, UCL, London, United Kingdom, 3Centre for Mathematics and Physics in the Life Sciences and EXperimental Biology (CoMPLEX), 4UCL, Institute of Neurology, London, United Kingdom, 5MRC National Institute for Medical Research, London, United Kingdom

This study investigates the neurological characteristics of the Tc1 mouse model of Down syndrome using tensor based morphometry.

12:18 703.   Diffusion Kurtosis - A sensitive marker for Traumatic Brain Injury (TBI) 
Jiachen Zhuo1,2, Jake Mullins2,3, Julie Hazelton4, Jonathan Simon5, Su Xu1,2, Tuo Li6, Gary Fiskum4, and Rao Gullapalli1,2
1Radiology, University of Maryland School of Medicine, Baltimore, MD, United States, 2Core for Translational Research in Imaging at Maryland (C-TRIM), University of Maryland School of Medicine, Baltimore, MD, 3Neuroscience, University of Maryland Baltimore, Baltimore, MD, 4Anesthesiology and Center for Shock Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD, 5Electrical & Computer Engineering, University of Maryland, College Park, College Park, MD, 6University of Maryland School of Medicine

Understanding of tissue alterations at early stage following TBI is critical for injury management and prevention of severe secondary damage to the brain. In this study, both DTI and DKI parameters including mean diffusivity, fractional anisotropy & mean kurtosis (MK) were investigated for brain tissue damage at acute and sub-acute stages post-controlled cortical impact injury in a rat model. A significantly increased MK was observed at the sub-acute stage that was not picked up by MD & FA and correlated with increased astrocytic immunoreactivity. Our study indicates that diffusion kurtosis may serve as a sensitive marker for TBI.