This core will provide state-of-the-art bioimaging support for projects 1, 2, and 3, J. Zheng, H. Gendelman, and Y. Persidsky. The work will include quantitative magnetic resonance imaging (MRI), MR spectroscopic imaging (MRSI), and single photon emission computed tomography (SPECT). Two 7-Tesla small animal MRI/S systems, now operative at the University of Nebraska Medical Center, will provide quantitative neuroimaging and superparamagnetic iron oxide (SPIO) labeled cell tracking for rodent neuroAIDS animal models of HIV-1 associated dementia (HAD). One GammaMedica Ideas animal SPECT will be used in determining biodistribution of gamma emitter labeled cells or molecular probes and provides an excellent complement to MRI cell tracking methods. The image-processing laboratory has developed custom MRI/SPECT animal holders incorporating visible fiducial markers to allow coregistration of these two modalities. This allows anatomical details for SPECT images and validation of cell quantification by MRI. The bioimaging core methods also include quantitative mapping of blood-brain barrier permeability (project 3, Y. Persidsky), quantitative arterial spin labeled perfusion mapping, and quantitative proton MRSI (1H MRSI) (projects 2 and 3, H. Gendelman and Y. Persidsky). In addition, advanced imaging and spectroscopic analysis methods have been developed within the MRI/S core facility to allow automated mouse brain subimaging and coregistration/warping of imaging results with histology (all projects). This core will also support developmental therapeutics relevant to microglial activation in HAD. The long-term aims of these works are to assess the physiological MRI and biochemical 1H MRSI predictors of neuropathology and cell migration dynamics (MRI and SPECT) in mouse models of neuroAIDS. This will provide sensitive and specific screens of the onset and/or progression of disease as well as providing response kinetics to a variety of therapeutic interventions. The results obtained from this core will have direct applicability for monitoring the course of human neurodegenerative disorders. Significant modifications of the core were made in both focus and design so that it can unambiguously provide novel data that cannot readily be btained by histopathological examinations alone.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS043985-07
Application #
7983553
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
2009-03-01
Budget End
2010-02-28
Support Year
7
Fiscal Year
2009
Total Cost
$114,104
Indirect Cost
Name
University of Nebraska Medical Center
Department
Type
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198
Kiyota, Tomomi; Machhi, Jatin; Lu, Yaman et al. (2018) Granulocyte-macrophage colony-stimulating factor neuroprotective activities in Alzheimer's disease mice. J Neuroimmunol 319:80-92
McMillan, JoEllyn; Szlachetka, Adam; Zhou, Tian et al. (2018) Pharmacokinetic testing of a first generation cabotegravir prodrug in rhesus macaques. AIDS :
Olson, Katherine E; Bade, Aditya N; Namminga, Krista L et al. (2018) Persistent EcoHIV infection induces nigral degeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-intoxicated mice. J Neurovirol 24:398-410
Schutt, Charles R; Gendelman, Howard E; Mosley, R Lee (2018) Tolerogenic bone marrow-derived dendritic cells induce neuroprotective regulatory T cells in a model of Parkinson's disease. Mol Neurodegener 13:26
Thomas, Midhun B; Gnanadhas, Divya Prakash; Dash, Prasanta K et al. (2018) Modulating cellular autophagy for controlled antiretroviral drug release. Nanomedicine (Lond) 13:2139-2154
Kiyota, Tomomi; Machhi, Jatin; Lu, Yaman et al. (2018) URMC-099 facilitates amyloid-? clearance in a murine model of Alzheimer's disease. J Neuroinflammation 15:137
Kevadiya, Bhavesh D; Woldstad, Christopher; Ottemann, Brendan M et al. (2018) Multimodal Theranostic Nanoformulations Permit Magnetic Resonance Bioimaging of Antiretroviral Drug Particle Tissue-Cell Biodistribution. Theranostics 8:256-276
McMillan, JoEllyn; Szlachetka, Adam; Slack, Lara et al. (2018) Pharmacokinetics of a Long-Acting Nanoformulated Dolutegravir Prodrug in Rhesus Macaques. Antimicrob Agents Chemother 62:
Sillman, Brady; Woldstad, Christopher; Mcmillan, Joellyn et al. (2018) Neuropathogenesis of human immunodeficiency virus infection. Handb Clin Neurol 152:21-40
Zhou, Tian; Su, Hang; Dash, Prasanta et al. (2018) Creation of a nanoformulated cabotegravir prodrug with improved antiretroviral profiles. Biomaterials 151:53-65

Showing the most recent 10 out of 240 publications