Jacob Ellegood¹, Jason P Lerch¹, and R M Henkelman^1
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.

Chunlei Liu^1,2, Wei Li¹, G. Allan Johnson², and Bing Wu^1
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.

Cristina Cudalbu¹, Melanie Craveiro¹, Vladimir Mlynárik¹, Juliane Bremer², Adriano Aguzzi², and Rolf Gruetter^1,3
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.

Taeko Inoue¹, John P Leach¹, Daniela Marcano², Jacob Berlin², Thomas A Kent^3,4, James M Tour^2,5, and Robia G Pautler^1
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.

Lindsay K Hill¹, Karen C Briley-Saebo², Dung M Hoang¹, Asad Baig¹, Brian J Nieman³, Zahi A Fayad², and Youssef Z Wadghiri^1
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.

Vladimir Mlynarik¹, Lili Sun-Reimer¹, Sharon Janssens¹, Matthias Cacquevel², Hongxia Lei¹, Bernard Schneider², Patrick Aebischer², and Rolf Gruetter^1,3
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.

Lauri Juhani Lehto¹, Alejandra Sierra¹, Curtis Andrew Corum², Djaudat Idiyatullin², Michael Garwood², and Olli Heikki Gröhn^1
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.

Manisha Aggarwal¹, Susumu Mori¹, Michael I Miller², Wenzhen Duan³, and Jiangyang Zhang^1
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

Benjamin Sinclair^1,2, Jon Cleary², Marc Modat¹, Francesca Norris^2,3, Frances Wiseman⁴, Victor Tybulewicz⁵, Elizabeth Fisher⁴, Mark Lythgoe², and Sebastien Ourselin^1
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.

Jiachen Zhuo^1,2, Jake Mullins^2,3, Julie Hazelton⁴, Jonathan Simon⁵, Su Xu^1,2, Tuo Li⁶, Gary Fiskum⁴, and Rao Gullapalli^1,2
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.