Longitudinal absolute metabolite quantification of white and gray matter regions in healthy controls using proton MR spectroscopic imaging.

The purpose of this study was to evaluate quality parameters, metabolite concentrations and concentration ratios, and to investigate the reproducibility of quantitative proton magnetic resonance spectroscopic imaging ((1)H-MRSI) of selected white and gray matter regions of healthy adults. 2D-quantitative short-TE (1)H-MRSI spectra were obtained at 1.5T from the healthy human brain. Subjects (n = 12) were scanned twice with an interval of six months. Absolute metabolite concentrations were obtained based on coil loading, taking into account differences in sensitivity of the phased-array head coil. Spectral quality parameters, absolute metabolite concentrations, concentration ratios, and their reproducibility were determined and compared between time-points using a repeated measures general linear model. The quality of the spectra of selected brain areas was good, as determined by a mean spectral linewidth between 4.8 and 7.3 Hz (depending on the region). No significant differences between the two time-points were observed for spectral quality, concentrations, or concentration ratios. The mean intrasubject coefficient of variation (CoV) varied between 4.0 and 8.5% for total N-acetylaspartate, 7.2 and 10.8% for total creatine, 5.9 and 9.8% for myo-inositol, and 8.0 and 13.3% for choline, and remained below 20% for glutamate. CoV was generally lower when concentration ratios were considered. The study shows that longitudinal quantitative short-TE (1)H-MRSI generates reproducible absolute metabolite concentrations in healthy human white and gray matter. This may serve as a background for longitudinal clinical studies in adult patients.

Interferon beta-1b reduces black holes in a randomised trial of clinically isolated syndrome.

BACKGROUND: Multiple sclerosis (MS) is characterised by inflammatory lesions of the central nervous system. Interferon beta-1b (IFNB-1b) has been shown to improve clinical and magnetic resonance imaging (MRI) measures for patients with MS. OBJECTIVE: To evaluate whether IFNB-1b in patients presenting with clinically isolated syndromes (CIS) prevented persisting T1 hypointensities on MRI (persistent black holes (PBHs)). METHODS: In the placebo-controlled phase, patients (n = 468) were initially randomised to IFNB-1b (n = 292) or placebo (n = 176) for two years or clinically definite MS (CDMS). In the open-label phase (n = 418), both groups were offered IFNB-1b for up to five years. Lesions were classified as PBHs if T1 hypointensity persisted throughout the last available scan (minimum time one year). RESULTS: A total of 435 patients were evaluable for analysis. The number of PBHs/patient was lower in the early rather than the delayed treatment arm during both phases (.42 vs .71, p = .0102 and .70 vs 1.17, p = .0121). Exploratory analyses identified baseline characteristics that affected rate of conversion. CONCLUSIONS: Although the rate of lesions that converted to PBH showed no significant differences between groups, the numbers of PBHs per patient out of new lesions was significantly lower in IFNB-1b patients compared to patients on placebo. TRIAL REGISTRATION NUMBER: NCT00544037.