Biochemical changes in the frontal lobe of HIV-infected individuals detected by magnetic resonance spectroscopy

Abstract

We have developed a proton magnetic resonance spectroscopy method that selectively can sample cortical gray matter and adjacent white matter in the frontal lobe. We have used this approach to study a group of patients (n ‫؍‬ 7) infected with HIV and clinical manifestations of the AIDS dementia complex (ADC), a group of patients (n ‫؍‬ 8) infected with HIV without any indications of ADC, and seven controls. The patients without ADC had a statistically significant increase in the ratio of myo-inositol to creatine in white matter compared with normal controls. In contrast, the group of patients with ADC had almost normal levels of myo-inositol to creatine in both gray matter and white matter and showed a statistically significant decrease in the N-acetylaspartate to creatine ratio in gray matter compared with either the normal controls or the patients without ADC. Patterns of spectral abnormalities correlated with neuropsychological measures of frontal lobe dysfunction, suggesting that the evaluation of frontal lobe metabolism by magnetic resonance spectroscopy can play a role in the early detection of ADC, in determining its progression, and in assessing responses to therapeutic interventions.

Assessing multiple-group diagnostic problems with multi-dimensional receiver operating characteristic surfaces: Application to proton MR Spectroscopy (MRS) in HIV-related neurological injury

“…This strongly suggests that significant NAA/Cr decreases in the white matter are associated with overt clinical disease (ADC group), but there is no evidence of neurological damage (reflected by decreases of NAA/Cr) among HIV-positive persons who do not demonstrate clinically manifested neurological disease. This result is consistent with a number of previous reports that suggest that, while inflammation (as reflected by changes in MI/Cr and Cho/Cr) is observable throughout HIV infection, NAA/Cr decreases happen later during progression to clinically manifested neurological disease (Tracey et al 1996;Lopez-Villegas et al 1997). …”

“…Cho/Cr and MI/Cr have been reported to increase and NAA/Cr to decrease with progressive neurological injury (Tracey et al 1996;Lopez-Villegas et al 1997), so they are candidate markers for HIV-related damage to the central nervous system. Metabolite data were derived from subjects with a diagnosis of AIDS dementia complex (ADC).…”

In vivo 1H MRS of brain injury and repair during acute SIV infection in the macaque model of neuroAIDS

“…Additionally, several MRS studies of HIV-infected individuals have demonstrated early elevations of Cho/Cr and/or MI/Cr, with decreases in NAA/Cr more commonly observed later in the progression of the disease (7,24). While human MRS studies have been performed only during chronic HIV infection, similarities to our results are compelling, and suggest that chronic HIV infection incites brain metabolic responses that are similar to the acute SIV (and probably HIV) situation.…”

“…MRS studies performed at 1.5 T of the frontal lobes of HIV-infected patients have demonstrated increased Cho/Cr (9,22,23), increased MI/Cr (22,24), and decreased NAA/Cr (22-24). Additionally, several MRS studies of HIV-infected individuals have demonstrated early elevations of Cho/Cr and/or MI/Cr, with decreases in NAA/Cr more commonly observed later in the progression of the disease (7,24).…”

Changes in MRS neuronal markers and T cell phenotypes observed during early HIV infection

“…Significant reductions in NAA/Cr were observed in the frontal gray matter tissue of relatively healthy, cognitively asymptomatic (or even with ADC score 0.5), chronically HIV-infected subjects. 32 Imaging results have shown that chronically infected subjects lacking cognitive impairment have extensive thinning (Ϫ15%) of the cortical gray matter compared to controls. 33 MRS results of early infection imply that changes in the frontal cortex may begin within the first few months of infection.…”