3 T Two-Dimensional Cerebral MRS in HIV Youths

Margaret A. Keller, LA Biomedical Research Institute at Harbor-UCLA Medical
Basic-Applied Clinical

Scientific Abstract: 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. The aging population of adolescents and young adults who were infected vertically from the mother provide a unique, clinically stable, chronically HIV-infected group of patients whom we have already demonstrated have sub clinical CNS disease using magnetic resonance spectroscopy (MRS). It is our plan to identify abnormalities in this group that can be adapted for study in adult patients with HIV. 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 scanners and one -dimensional MRS (1D-MRS) techniques. The goals of this study are to improve detection of abnormal cerebral metabolites in HIV - infected patients by using a two -dimensional technique (2D-MRS) with a 3 Tesla scanner and to correlate abnormal cerebral metabolites with performance on neurocognitive tests. A 3T scanner is expected to offer considerable improvement over the 1.5 T scanner when studying cerebral metabolites in terms of improved signal to noise ratios (SNR) and lower coefficients of variance (C.V.). 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. The time interval between the second and third radiofrequency pulses is incrementally increased to encode the frequencies along a second time dimension. Our group is the only group that has studied two dimensional MRS of cerebral metabolites in HIV infected patients. 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 will be determined. Creatine is an energy metabolic reference marker and choline is also a reference metabolite which detects membrane turnover, myelination, and gliosis. The 3 Tesla scanner combined with 2D-MRS also provides the ability to study glutathione and choline groups, potentially additional markers of central nervous system (CNS) damage by the HIV virus. The specific aims of this study are to compare GABA, mI, choline groups, GSH and other metabolites in the left frontal brain and basal ganglia of 15 HIV-infected patients and 15 control subjects. Both of these areas of the brain have been documented by autopsy studies and MRS to be involved in the central nervous system pathology of HIV. The hypotheses are that GABA and mI ratios will be increased in HIV- infected patients and that elevation of these metabolites will correlate with poorer performance on a panel of neurocognitive tests of executive funtioning, fine motor activity, and attention. Reliable identification of adult or adolescent HIV-infected patients by 2D-MRS (3T) with abnormal cerebral metabolites and sub clinical brain involvement may require starting therapy earlier than CD4 count criteria would indicate or changing existing HAART therapy to antiretroviral medications with improved CNS penetration. This study may potentially improve the quality of life of HIV-infected patients and preserve the health of the central nervous system.