The present proposal is a supplement to the recently funded NeuroHIV Magnetic Resonance Spectroscopy Consortium grant (PI: Navia R01NS036524-05). The parent grant is a longitudinal study of brain metabolite changes and cognitive impairment associated with advancing HIV disease in the era of anti-retroviral therapy (ART). This supplement aims to support state-of-the-art longitudinal analyses of the structural MRI data that is automatically collected as part of the parent consortium grant. The present study will allow us to identify multiple MRI signatures of brain dysfunction associated with HIV, and in turn define the evolutionary stages of brain involvement in HIV. ART has dramatically improved survival rates among HIV patients, though the extent to which these agents provide lasting benefits to the brain remains unresolved. There is accumulating evidence that despite good peripheral viral suppression, a significant amount of HIV-associated brain injury continues to occur. In vivo volumetric magnetic resonance imaging (MRI) provides a sensitive measure of regional and specific HIV- associated brain abnormalities. The MRS Consortium is collecting neuroimaging, immunological/virological and cognitive data from 310 HIV subjects with a history of advanced HIV disease on stable ART and at different stages of immunological and neurocognitive compromise. Follow-up assessments occur every 26-32 weeks (including MRI). The T1 and dual echo (proton density/T2) sequences from each time point will be analyzed using semi-automated methods including segmentation, voxel based morphometry and automatic anatomical labeling in order to ascertain the extent and severity morphometric change in treated HIV patients. The primary aims include: 1) To examine the evolution/progression of brain parenchymal fraction (BPF), frontal lobe, basal ganglia, hippocampal, and corpus callosum atrophy associated with HIV infection relative to MRS markers of inflammation (Ml/Cr, and Cho/Cr) and neuronal health (NAA/Cr); 2) To assess the temporal relationships between change in MRS measures, volumetric loss, and progression of cognitive impairment; and 3) To identify host and viral factors (e.g., age, CD4 count, chemokines, and HIV RNA) that may predict risk for structural brain atrophy. We propose to derive multivariate longitudinal models and examine the CMS effects of HIV as a dynamic system of interrelated factors. The establishment of neuroanatomical sequelae among HIV subjects on ART will have critical ramifications for cognitive outcome as well as provide additional targets for therapeutic outcome. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS036524-07S1
Application #
7168025
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Wong, May
Project Start
1997-04-01
Project End
2010-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
7
Fiscal Year
2006
Total Cost
$486,390
Indirect Cost
Name
Tufts University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
039318308
City
Boston
State
MA
Country
United States
Zip Code
02111
Anderson, Albert M; Harezlak, Jaroslaw; Bharti, Ajay et al. (2015) Plasma and Cerebrospinal Fluid Biomarkers Predict Cerebral Injury in HIV-Infected Individuals on Stable Combination Antiretroviral Therapy. J Acquir Immune Defic Syndr 69:29-35
Daiello, Lori A; Gongvatana, Assawin; Dunsiger, Shira et al. (2015) Association of fish oil supplement use with preservation of brain volume and cognitive function. Alzheimers Dement 11:226-35
Harezlak, J; Cohen, R; Gongvatana, A et al. (2014) Predictors of CNS injury as measured by proton magnetic resonance spectroscopy in the setting of chronic HIV infection and CART. J Neurovirol 20:294-303
Posse, Stefan; Otazo, Ricardo; Dager, Stephen R et al. (2013) MR spectroscopic imaging: principles and recent advances. J Magn Reson Imaging 37:1301-25
Gongvatana, Assawin; Harezlak, Jaroslaw; Buchthal, Steven et al. (2013) Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy. J Neurovirol 19:209-18
Zhu, Tong; Zhong, Jianhui; Hu, Rui et al. (2013) Patterns of white matter injury in HIV infection after partial immune reconstitution: a DTI tract-based spatial statistics study. J Neurovirol 19:10-23
Chang, Linda; Cloak, Christine C; Jiang, Caroline S et al. (2012) Lower glial metabolite levels in brains of young children with prenatal nicotine exposure. J Neuroimmune Pharmacol 7:243-52
Randolph, Timothy W; Harezlak, Jaroslaw; Feng, Ziding (2012) Structured penalties for functional linear models-partially empirical eigenvectors for regression. Electron J Stat 6:323-353
Inacio, Vanda; Turkman, Antonia A; Nakas, Christos T et al. (2011) Nonparametric Bayesian estimation of the three-way receiver operating characteristic surface. Biom J 53:1011-24
Torelli, Federico; Moscufo, Nicola; Garreffa, Girolamo et al. (2011) Cognitive profile and brain morphological changes in obstructive sleep apnea. Neuroimage 54:787-93

Showing the most recent 10 out of 38 publications