Tong Zhu1, Jianhui Zhong1, Rui Hu2, Wei Tian1, Sven Ekholm1, Constantin Yiannoutsos3, Ron Cohen4, Bradford Navia5, Michael Taylor6, Eric Daar7, Elyse Singer8, Thomas Campbell9, Deborah McMahon10, Yuen So11, Giovanni Schifitto1,12
1Dept. Imaging Sciences, University of Rochester, Rochester, NY, USA; 2Dept. Biostatistics, University of Rochester, Rochester, NY, USA; 3Division of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, USA; 4The Miriam Hospital, Brown University, Providence, RI, USA; 5Tufts University School of Medicine, Boston, MA, USA; 6University of California at San Diego, La Jolla, CA, USA; 7UCLA/Harbor, Torrance, CA, USA; 8UCLA, Los Angeles, CA, USA; 9University of Colorado, Denver, CO, USA; 10University of Pittsburgh, Pittsburgh, PA, USA; 11Stanford University, Palo Alto, CA, USA; 12Dept. Neurology, University of Rochester, Rochester, NY, USA
It is well established that HIV infection is associated with injury to the central nervous system (CNS) that can lead to cognitive impairment, including dementia. In this study, we used diffusion tensor imaging (DTI) and specifically Tract-Based Spatial Statistics to further investigate changes in white matter structures across the entire brain in HIV-infected subjects. The correlation between longitudinal changes in DTI and neuropsychological test scores were also evaluated to further investigate the structural-functional connection during the progression of CNS injury due to HIV infection. Results from this study show significantly decreased FA and increased MD values in multiple white matter structures as the disease progresses from neuroasymptomatic (HIV+NA) to cognitive impairment (HIV+CI). Compared to controls, in the early stages of HIV-associated CNS injury, significantly increased MD values were observed only within fiber bundles that are mainly associated with the posterior areas of the frontal and the parietal lobes. As CNS injury progresses, DTI changes were also seen in fiber bundles connecting to the prefrontal lobe, including the genu of the corpus callosum and the anterior corona radiata. Our results suggest that the combinations of DTI parameters such as FA and MD can differentiate control subjects from HIV+ infected subjects with and without cognitive impairment. The results also suggest a transition with more involvement of the frontal lobes in those subjects that develop cognitive impairment. The correlation with disease duration is consistent with this possibility. Among the different cognitive domains tested, verbal fluency had the highest correlation with DTI parameters. It is of interest that this cognitive domain is sub-served by neuronal circuitry that involves both the temporal and frontal lobes. As part of an ongoing project, we expect further validations of these results in future longitudinal analyses.