Nathalie Just¹, and Rolf Gruetter^1,2
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.

Laura-Adela Harsan¹, Marco Reisert¹, Annette Merkle¹, Jürgen Hennig¹, and Dominik von Elverfeldt^1
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.

Lisa M Gazdzinski¹, Kyle Cormier¹, C Shun Wong^2,3, Jason P Lerch¹, and Brian J Nieman^1
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.

Pascal Sati¹, Peter Van Gelderen², Afonso C Silva³, Hellmut Merkle⁴, Daniel S Reich¹, and Jeff H Duyn^2
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.

Friedrich Wetterling¹, Nagesh Shanbhag², Lothar Schilling², Stefan Kirsch¹, and Lothar Rudi Schad^1
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.

Alexandru Parlog^1,2, Marco Reisert¹, Dominik von Elverfeldt¹, Ildiko Dunay², and Laura-Adela Harsan^1
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.

David M. Wilson¹, John Kurhanewicz¹, and Kayvan R. Keshari^1
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.

Helmar Waiczies^1,2, Stefano Lepore^1,2, Jason M Millward^3,4, Bettina Purfürst⁵, Thoralf Niendorf^2,3, and Sonia Waiczies^1,2
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.

Eva-Maria Ratai^1,2, Robert J Fell¹, Julian He^1,2, Michael Piatak³, Jeffrey D Lifson³, Tricia H Burdo⁴, Jennifer Campbell⁴, Patrick Autissier⁴, Lakshmanan Annamalai⁵, Eliezer Masliah⁶, Susan V Westmoreland^2,5, Kenneth C Williams⁴, and R Gilberto González^1,2
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.

Ji-Yeon Suh¹, Shunning Huang¹, Dmitriy N. Atochin², Paul L. Huang², Emmanuel S Buys³, Peter Brouckaert⁴, Jeong Kon Kim^1,5, Woo Hyun Shim¹, Seon Joo Kwon¹, and Young Ro Kim^1
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.