Cerebral metabolites in HIV-infected children followed for 10 months with 1H-MRS.

BACKGROUND: Previous studies have shown that HIV-infected children have abnormal cerebral metabolites, measured by proton MR spectroscopy (1H MRS), but the stability of these measurements over time has not been described in HIV-infected children. The authors recently reported a study of cerebral metabolites in 20 HIV-infected children (6 to 16 years of age); the current study followed 12 of these children (10.0 years +/- 3.7 years) and repeated the MR spectroscopy at 24.1 +/- 3.7 weeks and 42.2 +/- 3.5 weeks following the entry time with repeated neuropsychological testing. METHODS: 1H MR spectra were acquired at 1.5 T (GE Signa, PRESS localization, repetition time = 3,000 msec, echo time = 30 msec). Five brain regions were studied: right frontal white matter, left frontal white matter, right basal ganglia, right hippocampus, and midfrontal gray matter. The concentrations of N-acetylaspartate (NAA), choline (CHO), creatine (CR), and myo-inositol (mI) and the ratio of each metabolite to CR were determined. RESULTS: There were no changes in the metabolite concentrations or metabolite/CR ratios at the three time periods. Similarly, during this follow-up period, HIV-positive children showed no changes in clinical signs, HIV viral loads, CD4%, or CD4 counts, except for improved spatial memory with repeat testing. CONCLUSION: In a clinically and neurologically stable group of HIV-infected children, cerebral metabolites were stable over a 10-month time period, suggesting that it is possible to assess changes in cerebral metabolites as a measure of cerebral health, but longer follow-up in a larger sample is needed.

Altered neurometabolite development in HIV-infected children: correlation with neuropsychological tests.

BACKGROUND: HIV-infected children have abnormal cerebral metabolites, measured by proton MR spectroscopy ((1)H-MRS), but how these abnormalities relate to brain function is unclear. METHODS: Metabolite concentrations in five brain regions of 20 HIV-infected and 13 control children were measured, and these findings were correlated with age, log(10) plasma viral load, CD4 count, and neuropsychological scores. RESULTS: Compared with control subjects, HIV patients had decreased choline concentration [Cho] in left frontal white matter (LFW) (-12%; p = 0.04); those with high viral load (>5,000 HIV RNA copies/mL) had decreased right basal ganglia (RBG) [Cho] (-15%; p = 0.005), and [Cr] (-13%; p = 0.02). Patients with high viral load also had higher [Cho] in the midfrontal gray matter (MFG) (+25%; p = 0.002) and lower myo-inositol [Ins] in the RBG (-18%; p = 0.04) than patients with low HIV viral load. N-Acetyl aspartate concentration ([NAA]) correlated with age in right frontal white matter (RFW) (r = 0.59, p = 0.04), LFW (r = 0.66, p = 0.02), and right hippocampus (RHIP) (r = 0.69, p = 0.02) only in control subjects. In contrast, [Ins] correlated with age in both RFW and LFW (r = 0.71, p = 0.0006; r = 0.65, p = 0.006) only in the HIV patients. Log(10) plasma viral load correlated positively with [Ins] in RFW (r = 0.54, p = 0.02) and [Cho] in MFG (r = 0.49, p = 0.04). Compared with control subjects, HIV patients had poorer spatial memory (p = 0.045) and delayed spatial memory correlated with [Cho] in RHIP (r = 0.68, p = 0.02). CONCLUSIONS: These data suggest that normal brain development may be affected in children infected with HIV at birth, particularly evidenced by the lack of age-related increases in the neuronal marker [NAA]. Early, aggressive treatment of infants with HIV before development of encephalopathy is warranted.

Proton magnetic resonance spectroscopy of bipolar disorder versus intermittent explosive disorder in children and adolescents.

OBJECTIVE: The diagnosis of bipolar disorder in juveniles is controversial. This study was designed to compare proton magnetic resonance spectroscopy ((1)H MRS) in patients with bipolar disorder or intermittent explosive disorder, two groups with symptomatic overlap but categorical distinction. Children with intermittent explosive disorder designate patients whose illness clinically resembles pediatric bipolar disorder but does not satisfy DSM-IV criteria for mania. Based on the authors' previous report of higher levels of (1)H MRS cingulate myo-inositol/creatine in youngsters with bipolar disorder than in normal comparison subjects, they hypothesized that patients with bipolar disorder would have higher cingulate myo-inositol/creatine-phosphocreatine measurements than patients with intermittent explosive disorder and normal comparison subjects. METHOD: Myo-inositol levels were measured with a 2x2x2 cm(3) voxel placed in the anterior cingulate for acquisition of (1)H MRS in 10 patients with bipolar disorder, 10 patients with intermittent explosive disorder, and 13 normal comparison subjects. N-Acetylaspartate, choline moieties, creatine-phosphocreatine, and glutamate-glutamine metabolite levels were also measured. RESULTS: The patients with bipolar disorder showed significantly higher anterior cingulate myo-inositol/creatine-phosphocreatine and myo-inositol (mmol/liter) levels than the patients with intermittent explosive disorder and the normal comparison subjects. No significant differences were found across groups for myo-inositol or other metabolites in the occipital cortex. CONCLUSIONS: These data provide evidence that differences in the concentration of myo-inositol (mmol/liter) in the anterior cingulate cortex in (1)H MRS may differentiate these two populations. Follow-up studies involving larger samples may conclusively estimate the biological specificity between pediatric bipolar disorder and other disorders, which overlap clinically.

Theoretical and experimental investigation of the effect of proton transfer on the (27)al MAS NMR line shapes of zeolite-adsorbate complexes: an independent measure of solid Acid strength.

Assessing the degree of proton transfer from a Brønsted acid site to one or more adsorbed bases is central to arguments regarding the strength of zeolites and other solid acids. In this regard certain solid-state NMR measurements have been fruitful; for example, some (13)C, (15)N, or (31)P resonances of adsorbed bases are sensitive to protonation, and the (1)H chemical shift of the Brønsted site itself reflects hydrogen bonding. We modeled theoretically the structures of adsorption complexes of several bases on zeolite HZSM-5, calculated the quadrupole coupling constants (Q(cc)) and asymmetry parameters (eta) for aluminum in these complexes and then in turn simulated the central transitions of their (27)Al MAS NMR spectra. The theoretical line width decreased monotonically with the degree of proton transfer, reflecting structural relaxation around aluminum as the proton was transferred to a base. We verified this experimentally for a series of adsorbed bases by way of single-pulse MAS and triple quantum MQMAS (27)Al NMR. The combined theoretical and experimental approach described here provides a strategy by which (27)Al data can be applied to resolve disputed interpretations of proton transfer based on other evidence.

Cross-polarization from the dipolar reservoir under the mismatched Hartmann-Hahn condition.

Cross-polarization from the dipolar reservoir for a range of mismatched Hartmann-Hahn conditions has been considered. Experiment, in general, agrees with the dispersive Lorentzian behavior expected on the basis of quasi-equilibrium theory. It is observed that inclusion of additional mechanisms of polarization transfer lead to an improvement of the fit of the experimental results. The utility of extending the technique to the case of ordered long chain molecules, such as liquid crystals, for the measurement of the local dipolar field is also presented.