Single voxel ¹H MRS is a non-invasive brain imaging method that provides quantitative neurochemical information in selected regions of interest. More specifically, it provides information regarding the nature, the distribution and the biochemical significance of brain injury. In a multi-disciplinary research framework, ¹H MRS is a powerful tool that can shed light on new neuropathogenic mechanisms.

Single voxel ¹H MRS has historically been a method of choice to detect early HIV-related brain damage. The typical profile shows increased myo-inositol in the frontal white matter and decreased N-acetyl Aspartate in the basal ganglia with partial resolution with initiation of combined antiretroviral therapy (cART). This profile reflects neuronal injury in the basal ganglia and neuroinflammation in the white matter. This is in agreement with the fact that HIV-associated neurocognitive disorder is conceptualized as a striato-frontal type of disorder.

However, HIV-infected persons are now living almost as long as the general population since cART introduction. In this context, whether brain aging, cardio-vascular mediated brain injury and neurodegeneration are associated or compounded by the long-term presence of HIV in brain tissues have become major scientific questions. Interestingly, the profile of ¹H MRS changes in normal and pathological brain aging has been relatively well characterized. Therefore ¹H MRS can provide valuable information for characterizing the extent and the nature of age-related, neurovascular and neurodegenerative injuries in chronic HIV infection where there is evidence of long-term brain immune dysregulation.

After critically reviewing the ¹H MRS findings in HIV infection prior to the cART era, we will summarize the cART era findings in the light of whether previous limitations were adequately addressed. We will then focus on the major findings of the cART era in relation to brain aging, neurovascular injury and neurodegeneration and specifically how ¹H MRS can address these questions as a unimodal and multi-modal imaging method. We will present the most recent international findings including those from our research group in Sydney.