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.
These results indicate that patients with basal ganglia calcifications frequently have a subcortical pattern of neuropsychological dysfunction and behavioral changes that are known to be associated with alterations of the frontal-limbic-basal ganglia circuits. The pattern of neuropsychological impairment is consistent with basal ganglia damage. However, poor performance in other neuropsychological tests suggest additional involvement of other connected networks.
Elevated brain lactate has been observed by in vivo proton MRS in different pathological situations. The origin of this lactate remains controversial. The possibility that it was produced by the metabolism of phagocytic cells has been proposed. To investigate this hypothesis, the authors have employed high-resolution proton MRS to monitor changes in glucose, lactate, and other metabolites in the medium used to culture human monocyte-derived macrophages in vitro. Results show that the differentiation of human monocytes/macrophages in the presence of physiological stimulating factors (M-CSF or GM-CSF) was associated with an increase in lactate production and glucose utilization. The present results are consistent with the hypothesis that lactate detected by proton MRS in vivo may be produced by the metabolism of macrophages when infiltrates of these cells are present. The possible extrapolation of the authors' finding to the in vivo situation and its relevance are discussed.
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