Neuroimaging has been shown to be a viable tool for detection of CNS abnormalities, clinical management of HIV-infected patients, and to better understand the pathogenesis of HIV infection in the brain. Diffusion tensor imaging (DTI) provides information about the integrity of white matter tracts and may be helpful especially in studying diseases associated with demyelination (1, 2). DTI parameters, including fractional anisotropy (FA), which is sensitive to white matter integrity, and mean diffusivity (MD), which quantifies water molecular diffusion at levels approximating cellular dimensions, were determined for aggregate 3D volumes of interest. We used the well-validated International HIV Dementia Scale (HDS) a brief and reliable measure of global cognitive function that is reliably able to identify features of HIV-associated dementia (3). Myelin loss and axonal damage are both observed in white matter injuries that might occur in HIV. Hence, in the current study, our specific aim was to determine whether HIV affects the DTI indices of FA and MD in specific regions of interest of HIV-positive adults in association with neurocognitive changes.We have scanned 16 HIV adults (mean age 45.8 years) five healthy controls (mean age 51.0 years) in 3T MRI scanner (Siemens Medical Systems, Germany) using a 16-channel head ‘receive’ coil with restraining foam pads to minimize head motion. A single-shot, spin echo EPI technique with alignment of the anterior/posterior commissure plane was performed with the following parameters: TR 11000 ms, TE 90 ms, FOV 256x 256 mm², acquisition matrix 128 x 128 zero-filled to 256 x 256, slice thickness 2 mm without gap, 85 slices and 1 average. The diffusion sensitizing gradients were applied along 64 noncollinear gradient encoding directions with b 1000 s/mm² with an acquisition without diffusion weighting (b0 s/mm²). Voxel-based morphometry (VBM) analysis was used for DTI processing. The diffusion-weighted volumes were first aligned to their corresponding non-diffusion-weighted images to minimize image distortion and reduce simple head motion. The diffusion tensor for each voxel was then assessed, and the diffusion tensor was diagonalized to obtain its 3 pairs of eigenvalues and eigenvectors. Two diffusion metrics, including FA and MD were calculated. These measurements are associated with the microstructural integrity of the white matter (WM) and are often applied to infer the structural characteristics of the local tissue environment. A brief neuropsychological test battery was administered to all participants to assess specific domains of attention, concentration, learning, memory and psychomotor speed.Significantly decreased FA was observed in HIV infected adults compared to healthy controls in the following locations: right and left cerebral white matter, right posterior cingulate gyrus and right superior parietal lobule. Also we observed significantly decreased MD in HIV patients compared to healthy controls in the following locations: left planum polare, left cerebral white matter, left central operculum, left precuneus, left and right superior frontal gyrus. Fig.1 shows the glass brain representation with projected axial/sagittal and coronal images of FA and MD maps. Table 1.shows FA and MD changes in the significant locations. Fig.3. shows the HDS of HIV patients and healthy controls. There was a significant decline of overall mean HDS score observed in HIV adults (13±2.8) compared to healthy controls (15.2±1.3). Lower FA may reflect greater degradation of the microstructure, such as age-related loss of myelination in the white matter, which might account for the slower performance on many tasks. Decreased FA values are in agreement with earlier reported DTI findings (4). Increased MD is associated with increased volume of the extracellular space or with decreased barriers to diffusion in white matter (5) thus it is usually a consequence of neuroinflammation or edema. Whereas the significance of decreased mean diffusivity, as found here, remains uncertain, it may again reflect the increased activity and connectivity in this region, which is thought to be present in patients with HIV. Even though declined HDS scores in attention, psychomotor and memory in HIV infected adults compared to healthy controls, significantly declined of HDS scores observed in the construction abilities of HIV infected adults (p<0.05). Tests that require drawing simple and complex two-dimensional figures or the construction of three-dimensional objects. These particularly severe deficits in visuospatial and visuoperceptual abilities in HIV patients compared to healthy control.Findings from our study indicate that DTI is a sensitive tool for correlating neuroanatomic pathologic features with specific cognitive deficits in patients with HIV infection.