Novel MRS Methods to Characterize MCMD

Cedars-Sinai Medical Center, West Hollywood CA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): This is a proposal to advance the use of the techniques of H magnetic resonance spectroscopy (MRS) and MRS imaging (MRSI) in HIV-1 infection. MRS quantification of glutamate - related to neuronal excitotoxicity and cell death - and myo-inositol - related to microglial proliferation - is acknowledged to be of growing significance in HIV-1 infection. To maximize their utility, further refinement is needed of the MRS techniques used to separate glutamine from glutamate and myo-inositol from taurine. After preliminary validation of this methodology, these measures will be related to both clinical [neuropsychological (NP) performance; minor cognitive-motor disorder (MCMD)] and pathophysiological indices (plasma HIV-1 RNA load; CD4 cell count; cytotoxic T lymphocyte count). We will recruit our sample from our renewed NIMH funded R-01 study examining the interaction of aging and HIV-1 infection on the foregoing measures. In that cohort, 327 participants in four groups - older HIV-1+, younger HIV-1+, older HIV-1- and younger HIV-1- - are anticipated to be available over the project period. This proposal will use a 3.0T Siemens Trio system in the frontal grey matter, the frontal subcortical white matter, and the basal ganglia. Those with a diagnosis of MCMD (n=25) will be compared to HIV-1+ individuals without NP impairment (n=25) and to a HIV-1- seronegative control group (n=25). The primary hypotheses relate to the association of increased glutamatergic transmission and myo-inositol concentrations with the diagnosis, symptom profile, and severity of MCMD. Secondary hypotheses relate increased glutamatergic transmission and myo-inositol concentrations to NP performance deficits in the domains of attention, information processing speed, working memory, episodic memory, visuoconstructive skills, abstraction/executive function, language, and motor skills. Support of this study would lead to a subsequent larger, longitudinal R01 proposal aimed at further investigating the impact of this methodological development. This research is significant in that it relates to the potential for increased clinical utility of the non-invasive, brief, in vivo technique of 'H MRS for measuring brain tissue metabolites directly from specified brain regions in order to document the diagnosis of HIV-1 associated MCMD as well as its progression and treatment response. [unreadable] [unreadable]