Prospective Utility of Cerebral Proton Magnetic Resonance Spectroscopy in Monitoring HIV Infection and Its Associated Neurological Impairment

Abstract

Neurological manifestations of HIV disease occur in most adults and children with AIDS. Many of those affected will inevitably suffer clinical neurological deficits involving mental function, movement, and sensation. Surprisingly, there are not as yet adequate monitoring systems to predict the onset and/or progression of HIV infection of the CNS. Neurological, neuropsychological, CSF, and magnetic resonance imaging (MRI) analyses cannot accurately detect mental deterioration during advancing HIV disease. Reports suggest that in vivo proton MR spectroscopy (1H MRS) of the brain could be a predictor of virus-induced neurological deterioration. H MRS can measure N-acetylaspartate (NAA), a metabolite present only in neurons. Decreased NAA reflects neuronal loss seen during HIV infection of brain. To uncover possible associations between NAA levels and HIV-induced neurological disease we performed serial 1H MRS brain tests in HIV-infected patients with or at risk for encephalopathy. Serial testing, for 1 year, of 10 patients showed that brain NAA levels decreased in all HIV-infected subjects. The most severe NAA reductions were associated with progressive neurological impairment. These findings suggest that NAA can be used as a noninvasive measure of neuronal loss in patients with HIV disease. Most important, the results suggest that 1H MRS could be used to monitor therapeutics directed against HIV infection within the CNS.

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

“…We found no significant differences in choline-containing compound (Cho)͞Cr levels between patients and controls, an observation in agreement with a previous report (20). However, other studies have shown increased Cho as a common finding in HIV-1-infected patients (22,24,25,27,36,39).…”

“…MRS studies on patients with HIV carried out with larger voxels in different regions of the brain have shown a correlation between the reduction in NAA and the severity of cognitive impairment (20,22,23,26,27). Our study shows that the decrease of NAA͞Cr in the frontal lobe correlates both with the degree of ADC and with neuropsychological measures of frontal lobe dysfunction, suggesting that ADC may be directly related to the degree of neuronal loss or dysfunction in the frontal cortex.…”

“…Previous MRS studies (20)(21)(22)(23)(24)(25)(26)(27)36), which have sampled regions containing both gray matter and white matter, have shown reductions in NAA͞Cr in patients with ADC. Using a high spatial resolution approach (0.36 cm 3 nominal voxel size) we have found decreased NAA͞Cr ratios predominantly in the gray matter in the frontal cortex of HIV-1-infected patients.…”

“…However, mild brain abnormalities detected on MRI need not reflect the presence of underlying HIV encephalopathy (19) nor show progression over time (20), suggesting that MRI may not be sensitive enough for the early detection and evaluation of the progression of ADC.…”

Whole body positron emission tomography imaging of simian immunodeficiency virus-infected rhesus macaques.

“…Magnetic resonance imaging and computed tomography are often used for the patient with AIDS to diagnose Nocardia asteroides infection (11), brain abnormalities (12,13), toxoplasmosis (14), and cytomegalovirus infections in the central nervous system (15). Toxoplasmosis, AIDS-associated myocarditis, abnormal bowel activity, and lymphocyte infiltration of salivary glands have been studied using 67Ga-citrate (16)(17)(18).…”