This K23 application requests a period of career development to study advanced methods in Magnetic Resonance (MR) imaging and exploit them to study HIV-Dementia (HIV-D). Emerging MR methods provide microstructural information concerning white matter that cannot be obtained using other imaging techniques. Diffusion Tensor Imaging (DTI) is a non-invasive technique that may be useful in studying white matter integrity in normal, diseased or degenerating tissue in vivo. HIV-Dementia (HIV-D) is characterized by various pathologies involving white matter. This study represents an opportunity to evaluate information uniquely revealed by DTI in the context of other meaningful biological and clinical parameters. Subjects in this investigation will include well-characterized patients from a large, longitudinal cohort study_ef HIV-D. Extensive data is available from semi-annual evaluations over a number of years, including biological markers derived from plasma and CSF, as well as information concerning neurocognitive and psychiatric functioning. This study will determine whether microstructural measures of white matter integrity, derived using DTI, bear a relation to measures of advancing HIV infection (e.g. viral load and immune activation), severity of dementia and specific neuropsychiatric sequelae. In addition, the DTI findings will be evaluated in the context of biological markers of theoretical interest, including select measures of inflammation (e.g. TNF ) and endothelial integrity (e.g. MMP-9). These findings will contribute to an understanding of the pathogenesis of HIV-D and may provide insights concerning other CNS disorders. Experience gained during the proposed award will lay the foundation for further independent investigations of neurobiological factors in HIV-D.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH066705-05
Application #
7103675
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Stoff, David M
Project Start
2002-08-01
Project End
2007-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
5
Fiscal Year
2006
Total Cost
$115,143
Indirect Cost
Name
Northwestern University at Chicago
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Du, Hongyan; Wu, Ying; Ochs, Renee et al. (2012) A comparative evaluation of quantitative neuroimaging measurements of brain status in HIV infection. Psychiatry Res 203:95-9
Ragin, Ann B; Wu, Ying; Ochs, Renee et al. (2011) Marked relationship between matrix metalloproteinase 7 and brain atrophy in HIV infection. J Neurovirol 17:153-8
Ragin, Ann B; Wu, Ying; Ochs, Renee et al. (2010) Biomarkers of neurological status in HIV infection: a 3-year study. Proteomics Clin Appl 4:295-303
Ragin, Ann B; Wu, Ying; Ochs, Renee et al. (2009) Serum matrix metalloproteinase levels correlate with brain injury in human immunodeficiency virus infection. J Neurovirol 15:275-81
Wu, Y; Storey, P; Carrillo, A et al. (2008) Whole brain and localized magnetization transfer measurements are associated with cognitive impairment in patients infected with human immunodeficiency virus. AJNR Am J Neuroradiol 29:140-5
Wu, Y; Storey, P; Cohen, B A et al. (2006) Diffusion alterations in corpus callosum of patients with HIV. AJNR Am J Neuroradiol 27:656-60
Ragin, A B; Wu, Y; Storey, P et al. (2006) Monocyte chemoattractant protein-1 correlates with subcortical brain injury in HIV infection. Neurology 66:1255-7
Ragin, A B; Wu, Y; Storey, P et al. (2006) Bone marrow diffusion measures correlate with dementia severity in HIV patients. AJNR Am J Neuroradiol 27:589-92
Ragin, Ann B; Wu, Ying; Storey, Pippa et al. (2005) Diffusion tensor imaging of subcortical brain injury in patients infected with human immunodeficiency virus. J Neurovirol 11:292-8
Ragin, Ann B; Storey, Pippa; Cohen, Bruce A et al. (2004) Whole brain diffusion tensor imaging in HIV-associated cognitive impairment. AJNR Am J Neuroradiol 25:195-200

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