In this resubmission the Investigator a series of longitudinal studies of HIV-infected persons using magnetic resonance spectroscopy (MRS) and imaging (MRI) to address the following hypotheses (as listed in the body of the application rather than in the Abstract): (1) That the ratio of N-acetyl aspartate to creatinine (NAA/Cr) in white matter and in the caudate nucleus will be lower in HIV-infected persons than in matched controls due to reduction in NAA, and that the ratio will decline more rapidly over time in patients than in matched controls. (2) That the caudate volumes as measured by MRI image analysis will be smaller in HIV-positive persons than in matched controls, and that these caudate volumes will decline more rapidly over time in HIV-positive persons than in matched controls. (3) That the decline in NAA/Cr ratio and caudate volume will be more rapid in HIV-positive women than in HIV infected men. (4) That CNS performance will decline with lower NAA/Cr ratios (in white matter and in the caudate nucleus) in HIV-positive persons relative to matched controls, and that the performance will parallel declines in NAA/Cr ratio over time. (5) That CNS performance deficits will be found with reduced caudate volumes as measured by MRI image analysis of HIV-positive persons relative to matched controls, and performance will parallel declines in the caudate volumes over time. These declines are expected to occur more rapidly in HIV-positive persons than in matched controls. (6) That the NAA/Cr ratio and caudate volume changes will relate to changes in CSF and systemic viral burden. The importance of these studies relates to clearer characterization and understanding of the effects HIV-1 on the CNS and, more practically, the hope that these methodologies might prove eventually useful in the timing and monitoring of therapies. The study is linked to a funded project assessing neurological disease in HIV-infected women.
| Chen, Yasheng; An, Hongyu; Zhu, Hongtu et al. (2009) White matter abnormalities revealed by diffusion tensor imaging in non-demented and demented HIV+ patients. Neuroimage 47:1154-62 |
| Tucker, Karen A; Robertson, Kevin R; Lin, Weili et al. (2004) Neuroimaging in human immunodeficiency virus infection. J Neuroimmunol 157:153-62 |
| Lee, S C; Zhao, M L; Hirano, A et al. (1999) Inducible nitric oxide synthase immunoreactivity in the Alzheimer disease hippocampus: association with Hirano bodies, neurofibrillary tangles, and senile plaques. J Neuropathol Exp Neurol 58:1163-9 |
