The overall goal of our study is to establish the predictive correlation between neuroimaging markers of NeuroAIDS and the discrete neuropathogenetic processes that occur as a result of Human Immunodeficiency Virus (HIV-1) infection of the Central Nervous System (CNS).
The correlation of whole-brain data from different neuroimaging modalities will be computed topographically and at multiple levels of resolution, via the registration of complementary data sets relative to the same subject; in vivo and ex vivo.
High-resolution MRI protocols, applied postmortem, will be used to localize and classify white matter (WM) signal abnormalities and to measure morphometric parameters relative to cortical and subcortical grey matter (GM). Secondly, DTI-based fractional anisotropy (FA) and mean Diffusivity (MD) maps, reflecting WM integrity will be registered to MRI volumetric data in order to highlight any discrepancy in the detection of macroscopic WM changes by different imaging modalities. These maps will also be registered to newly established DTI-based atlases of connectivity identifying major fiber tracts that are compromised by the lesions, and thus tracing specific functional networks affected by WM pathology. This component of the project will characterize, for each case, the contribution and relationship between grey matter and white matter HIV-related changes in generating observed neurobehavioral profiles. Subsequent whole-brain histopathological analysis, using computer-aided large-field microscopy and stereology will afford the microscopic localization and quantification of HIVE markers (viral burden, inflammation, axonal integrity and cortical degeneration). Our protocol allows for the precise topographic registration of neuropathological and imaging data using 2-dimensional (2D) and 3-dimensional (3D) routines and culminates in the translation, for each subject, of these postmortem correlations into the parameters contained in clinical images obtained in vivo.
The multimodal examination of brain specimens from individuals who have been well characterized radiologically, clinically, and behaviorally provides a unique context in which to develop the detailed correlation between specific neuropathology and imaging markers, and relate these to the characteristics of scans acquired in vivo. This translation is the key to understanding the pathological basis of those imaging markers that are clinically indispensable for the neurological diagnosis and the prognosis of the disease.
Funded by The National Institute of Mental Health (NIMH).