Few studies have described the metabolic substrates underlying neuropsychological performance in HIV infection or examined the specificity of these relationships. The authors performed magnetic resonance spectroscopic and neuropsychological evaluations on 61 patients with AIDS dementia complex (stages 1-3) and 39 HIV-positive neurologically asymptomatic individuals. N-acetylaspartate, a marker of mature neurons, choline and myoinositol, both markers of gliosis, and creatine, a reference marker, were measured in the basal ganglia, frontal white matter, and parietal cortex. The neuropsychological evaluation consisted of tests that measured gross and fine motor skills, psychomotor function, information processing speed, and verbal memory. The authors examined performance on individual subtests and an aggregate Z score based on eight subtests (NPZ-8), adjusted for age and education. The NPZ-8 was significantly higher in subjects with greater N-acetylaspartate/creatine in the frontal white matter and was lower in subjects with higher myoinositol/creatine in the basal ganglia. Particularly strong associations were found between measures of gross and fine motor function, which correlated positively with N-acetylaspartate/creatine in the frontal white matter and negatively with myoinositol/creatine in the basal ganglia. Similarly, cognitive processing speed was negatively correlated with myoinositol/creatine in the basal ganglia. In contrast, there were no statistically significant relationships between brain metabolite levels in the parietal cortex and neuropsychological function. This study provides convincing evidence that neuropsychological impairment is associated with reduced markers of mature neurons and increased markers of gliosis in the basal ganglia and frontal white matter. Neural changes as reflected by these metabolite levels may prove useful in identifying individuals at risk for neuropsychological impairment. Prospective studies are needed to elucidate the evolution of these changes in the setting of antiretroviral therapy.

White and gray matter volumes in different regions of the brain were greater or smaller in recovering, treated alcoholics. The findings suggest region-specific structural recovery from chronic alcohol-induced brain injury, but also region-specific long-term structural damage in abstinent alcoholics. White matter lesions were widespread in active drinkers and may partly resolve during long-term abstinence. Proton MR spectroscopic measures, as applied in this cross-sectional study, were largely ineffective in revealing metabolic effects of abstinence on the alcohol-damaged brain.

Off-resonance or pulsed on-resonance saturation pulses were used together with localized proton magnetic resonance spectroscopy in three brain regions of 20 healthy individuals. Statistically significant signal attenuations were observed for creatinecontaining metabolites in posterior-parietal brain (12%), basal ganglia (18%), and cerebellum (15%). N-acetyl-and cholinecontaining metabolites were not significantly attenuated upon application of saturation pulses in either brain region. The findings are interpreted to reflect possible magnetization transfer between pools of creatine-containing metabolites with different molecular mobility. Magn Reson Med 42:417-420, 1999.1999 Wiley-Liss, Inc.Key words: magnetization transfer; magnetic resonance spectroscopy; dipolar coupling; human brain; creatine Magnetization transfer (MT) techniques have been used in high-resolution NMR to investigate molecular structure and chemical reaction equilibria based on cross-relaxation and chemical exchange. After they were described by Wolff and Balaban in 1989 (1), these methods also found a place in in vivo MRI. The unique way of obtaining MT contrast has led to a range of new applications in the evaluation of pathologies such as multiple sclerosis, metastatic disease, and human immunodeficiency virus infection (e.g., ref.2). This unique contrast is created by saturating a motionally restricted pool of water bound to macromolecules (proteins or membranes) and observing the decreased magnetization of the bulk mobile water that is not associated with macromolecules. Although the exact mechanisms underlying these effects are still a matter of discussion, it is thought that both chemical exchange and through-space dipolar interactions are responsible for this MT effect on tissue water. Both off-resonance and on-resonance saturation methods are commonly used for selective saturation of the motionally restricted water pool that is not directly observable by standard in vivo MR methods.Recently, MT effects have also been reported for 1 H magnetic resonance spectroscopy (MRS)-detectable metabolites in brain (3)(4)(5)(6)(7)(8)(9)(10). MT experiments at high field strengths showed signal reductions of lactate in rat glioma tissue (7) and of creatine/phosphocreatine in rat brain (3-5) and in rat and mouse skeletal muscle (8,9). In addition, we reported signal intensity decreases of alcohol in the human brain at 1.5 T (10) and in rat brain (6) and rat brain membrane suspensions upon off-resonance saturation at high fields (11). These latter experiments gave evidence of the postulated existence of more than one pool of alcohol in brain, and they add to our understanding of mechanisms of alcohol-induced tolerance in heavy drinkers (12). An MR-invisible pool of brain alcohol and alcohol MT effects may also provide partial explanations for the commonly reported low MRS-visibility of alcohol in the brain upon using certain water suppression and localization methods. Detailed studies of MT effects in tissue not only provide a view of mechanisms gove...

Background-Proton magnetic resonance spectroscopy ( 1 H MRS) allows measurement of alcohol in the human brain after alcohol consumption. However, the quantity of alcohol that can be detected in the brain by 1 H MRS pulse sequences has been controversial, with values ranging from about 24% to 94% of the temporally concordant blood alcohol concentrations. The quantitation of brain alcohol is critically affected by the kinetics of alcohol uptake and elimination, by the relaxation times of the protons that give rise to the brain alcohol signal, and by the specifics of both pulse sequence timing and radio frequency pulse applications.