Two-Dimensional 3 Tesla MRS of the Brain in HIV- Infected Youth

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DESCRIPTION (provided by applicant): HIV in adults and children has become a chronic illness and there is a critical need to develop noninvasive, reliable techniques to detect sub clinical involvement of the brain by HIV. Magnetic resonance spectroscopy (MRS) permits the study of HIV effects on cerebral metabolites, markers of neuronal and glial cell health. Most previous investigations have used 1.5 Tesla (T) scanners and one-dimensional MRS (1D-MRS) techniques. The primary goal of this study is to use an improved technique, a two-dimensional MRS technique (2D-MRS) on a 3 T scanner, to detect abnormal cerebral metabolites in HIV-infected patients, and to correlate abnormal cerebral metabolites with performance on neurocognitive tests, in order to better assess brain development and function in these individuals. A 3T scanner is expected to offer improved signal to noise ratios (SNR) and lower coefficients of variance compared to 1.5 T. The use of 2D-MRS allows the detection of many additional metabolites compared to traditional 1D-MRS by converting a crowded, overlapping 1D-MRS spectrum to a better resolved 2D spectrum through the addition of a spectral dimension. Of particular interest are GABA, an inhibitory neurotransmitter and myo-inositol (mI), a glial cell marker for which elevation suggests ongoing inflammation. Metabolite ratios to reference metabolites and metabolite concentrations will be determined. The 3 Tesla scanner combined with 2D-MRS also provides the ability to study glutathione (GSH), an important cellular antioxidant protector molecule that could assess central nervous system damage by the HIV virus. The specific aims of this study are to compare GABA, mI, choline groups, GSH and other metabolites in the right frontal brain region and right basal ganglia of 30 HIV-infected patients and 30 control subjects. Both of these areas of the brain have been documented to be involved in the central nervous system pathology of HIV. The hypotheses are that GABA and mI will be increased in HIV-infected patients while GSH will be decreased and that the changes in concentrations of these metabolites will correlate with poorer performance on neurocognitive tests of executive functioning, fine motor activity, and attention. In addition to the better assessment of brain development and function, reliable identification of perinatally HIV-infected youths with abnormal cerebral metabolites and sub clinical brain involvement by 2D-MRS (3T) may also direct earlier therapy than the current CD4 count criteria would indicate or changing existing HAART therapy to antiretroviral medications with improved CNS penetration. This study could potentially improve the quality of life of HIV-infected youths and preserve the health of the central nervous system. PUBLIC HEALTH RELEVANCE This study plans to identify metabolite markers of HIV involvement of the brain using noninvasive magnetic resonance spectroscopy in perinatally HIV-infected youths. Cerebral metabolite levels will be correlated with performance on neuropsychological tests and will identify involvement of the brain before clinical detection. Such results could dictate earlier therapy in children and youths with high CD4 cells or a change in antiretroviral medication to better treat HIV infection of the brain and improve the quality of life and neurological health of the millions of children worldwide infected with HIV from the mother.