White matter abnormalities revealed by diffusion tensor imaging in non-demented and demented HIV+ patients

Abstract

HIV associated dementia (HAD) is the most advanced stage of central nervous system disease caused by HIV infection. Previous studies have demonstrated that patients with HAD exhibit greater cerebral and basal ganglia atrophy than non-demented HIV+ (HND) patients. However, the extent to which white matter is affected in HAD patients compared to HND patients remains elusive. This study is designed to address the potential white matter abnormalities through the utilization of diffusion tensor imaging (DTI) in both HND and HAD patients. DTI and T1-weighted images were acquired from 18 healthy controls, 21 HND and 8 HAD patients. T1 image-based registration was performed to 1) parcellate the whole brain white matter into major white matter regions, including frontal, parietal, temporal and occipital white matter, corpus callosum and internal capsule for statistical comparisons of the mean DTI values, and 2) warp all DTI parametric images towards the common template space for voxel-based analysis. The statistical comparisons were performed with four DTI parameters including fractional anisotropy (FA), mean (MD), axial (AD), and radial (RD) diffusivities. With Whitney U tests on the mean DTI values, both HND and HAD demonstrated significant differences from the healthy control in multiple white matter regions. In addition, HAD patients exhibited significantly elevated MD and RD in the parietal white matter when compared to HND patients. In the voxel-based analysis, widespread abnormal regions were identified for both HND and HAD patients, although a much larger abnormal volume was observed in HAD patients for all four DTI parameters. Furthermore, both region of interest (ROI) based and voxel-based analyses revealed that RD was affected to a much greater extent than AD by HIV infection, which may suggest that demyelination is the prominent disease progression in white matter.

Fig. 1

Four axial (top two panels) and coronal (bottom two panels) slices of the template T1 images and the corresponding parcellated major white matter regions including frontal, parietal, temporal, occipital white matter, corpus callosum and internal capsule, respectively.

Fig. 2

The mean (top panel) and standard deviation (bottom panel) maps of FA, MD, AD and RD (10⁻³ mm²/s for diffusivities) from all 47 subjects. For each DTI parameter, cross-sectional views of the mean and standard deviation maps are displayed with the same contrast to demonstrate the relative signal strength between them.

Fig. 3

The mean and standard deviation of the mean DTI parameters (FA, MD, AD and RD) for NORMAL, HND and HAD within frontal (FW), parietal (PW), temporal (TW) and occipital (OW) white matter, corpus callosum (CC) and internal capsule (IC). Symbols *, ** and *** indicate the statistical significant level of p<0.05, p<0.01 and p<0.001, respectively.

Fig. 4

The abnormal white matter regions detected in HND and HAD patient groups with voxel-based analysis in FA, MD, AD and RD. The affected brain areas with significantly reduced FA and elevated MD, AD, and RD in HND and HAD patient groups are superimposed upon the mean FA map of the healthy controls.

Fig. 5

The total volume of the identified significant regions by voxel-based analysis (cm³) with FA, MD, AD and RD, for HND and HAD patients in different major white matter regions.