A clearer understanding of risk factors for brain injury in early HIV infection is critical for rational intervention and neuroprotection efforts. Quantitative Magnetic Resonance (MR) Imaging methodologies can be used to generate objective measurements of the brain at different levels of analysis. This investigation will exploit these noninvasive technologies to systematically quantify brain injury in HIV patients in early stages of infection in order to identify factors associated with increased risk of neurological progression. The focus of this investigation concerns activated monocytes in the peripheral circulation and factors that influence monocyte trafficking (TNFa and MCP-1, in plasma, CSF). Immunologic (CD4+ and CD8+) and virologic (HIV RNA in plasma, CSF) factors will also be evaluated. These potential determinants of neurological progression will be evaluated for patterns of relationship to objective measurements of brain injury and cognitive impairment in HIV patients in early (within 6 months of seroconversion) and asymptomatic HIV infection. All subjects will be evaluated at baseline and at a follow-up assessment, two years post-baseline. Automated segmentation algorithms will be used to derive volume fractions of the normalized brain parenchyma and of specific tissue classes (gray matter, white matter and CSF). Diffusion Tensor Imaging (DTI) will be used to measure microstructural changes in the whole brain and in specific regions that are vulnerable to injury in HIV patients, including the basal ganglia and deep white matter. The bone marrow will also be interrogated with quantitative MR methodologies. The latter imaging studies are motivated by evidence that immune activation in the marrow influences monocyte trafficking to the brain, as well as HIV replication, and therefore may represent a critical determinant of neurological injury. The in vivo marrow measurements will be examined for the degree of relationship to brain injury and neurocognitive impairment. The histological significance of these measurements will be evaluated with respect to levels of activated monocytes in the peripheral circulation and marrow biopsy findings of monocyte expansion and hypercellularity. Magnetic Resonance techniques for measuring the brain will be used to determine if injury occurs in early HIV infection. These techniques will also be used to determine whether specific factors are associated with changes in the brain in early and asymptomatic stages of HIV infection. Changes occurring in the bone marrow will also be studied as indicators of increased risk of brain injury in HIV patients.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Stoff, David M
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Northwestern University at Chicago
Schools of Medicine
United States
Zip Code
Ragin, Ann B; Wu, Ying; Gao, Yi et al. (2015) Brain alterations within the first 100 days of HIV infection. Ann Clin Transl Neurol 2:12-21
Cao, Bokai; Kong, Xiangnan; Kettering, Casey et al. (2015) Determinants of HIV-induced brain changes in three different periods of the early clinical course: A data mining analysis. Neuroimage Clin 9:75-82
Cao, Bokai; Kong, Xiangnan; Zhang, Jingyuan et al. (2015) Identifying HIV-induced subgraph patterns in brain networks with side information. Brain Inform 2:211-223
Cao, Bokai; He, Lifang; Kong, Xiangnan et al. (2014) Tensor-based Multi-view Feature Selection with Applications to Brain Diseases. Proc IEEE Int Conf Data Min 2014:40-49
Kelly, Sean G; Taiwo, Babafemi O; Wu, Ying et al. (2014) Early suppressive antiretroviral therapy in HIV infection is associated with measurable changes in the corpus callosum. J Neurovirol 20:514-20
He, Lifang; Kong, Xiangnan; Yu, Philip S et al. (2014) DuSK: A Dual Structure-preserving Kernel for Supervised Tensor Learning with Applications to Neuroimages. Proc SIAM Int Conf Data Min 2014:127-135
Sidharthan, Shawn; Hutten, Ryan; Glielmi, Christopher et al. (2013) Hippocampal magnetization transfer ratio at 3T: validation of automated postprocessing and comparison of quantification metrics. J Neuroimaging 23:484-90
Kong, Xiangnan; Yu, Philip S; Wang, Xue et al. (2013) Discriminative Feature Selection for Uncertain Graph Classification. Proc SIAM Int Conf Data Min 2013:82-93
Li, Suyang; Wu, Ying; Keating, Sheila M et al. (2013) Matrix metalloproteinase levels in early HIV infection and relation to in vivo brain status. J Neurovirol 19:452-60
Becker, James T; Maruca, Victoria; Kingsley, Lawrence A et al. (2012) Factors affecting brain structure in men with HIV disease in the post-HAART era. Neuroradiology 54:113-21

Showing the most recent 10 out of 22 publications