Intra- and inter-site reproducibility of human brain single-voxel proton MRS at 3 T.

INTRODUCTION: Clinical trials that involve participants from multiple sites necessitate standardized and reliable quantitative MRI outcomes to detect significant group differences over time. Metabolite concentrations measured by proton MRS (1 H-MRS) provide valuable information about in vivo metabolism of the central nervous system, but can vary based on the acquisition and quantitation methods used by different MR sites. Therefore, we investigated the intra- and inter-site reproducibility of metabolite concentrations measured by 1 H-MRS on MRI scanners from a single manufacturer across six sites. METHODS: Five healthy controls were scanned twice within 24 h at six participating 3 T MR sites with large single-voxel PRESS (TE/TR/NSA = 36 ms/4000 ms/56) and anatomical images for voxel positioning and correction of partial volume relaxation. Absolute metabolite concentrations were calculated relative to the T1 and T2 relaxation corrected signal from water. Intra- and inter-site reproducibility was assessed using Bland-Altman plots and intra- and inter-site coefficient of variation (CoV) as well as intra- and inter-site intra-class correlation coefficient. RESULTS: The median intra-site CoVs for the five major metabolite concentrations ([NAA], [tCr], [Glu], [tCho] and [Ins]) were between 2.5 and 5.3%. Inter-site CoVs were also low, with the median CoVs for all metabolites between 3.7 and 6.4%. Metabolite concentrations were robust to small inconsistencies in voxel placement and site was not the driving factor in the variance of the measurement of any metabolite concentration. Between-subject differences accounted for the majority of the concentration variability for creatine, choline and myo-inositol (42-65% of the variance). CONCLUSION: A large single-voxel 1 H-MRS acquisition from a single manufacturer's MRI scanner is highly reproducible and reliable for multi-site clinical trials.

Multicenter measurements of myelin water fraction and geometric mean T2 : intra- and intersite reproducibility.

PURPOSE: To assess the reproducibility of myelin water fraction (MWF) and geometric mean T2 (GMT2 ), which are in vivo markers of pathological changes underlying disability and progression in diseases such as multiple sclerosis. MATERIALS AND METHODS: Five healthy volunteers were scanned twice within 24 hours at six different sites using the same manufacturer's 3T magnetic resonance (MR) system. T2 distributions were produced by fitting multiecho 3D T2 data using non-negative least squares, with stimulated echo correction. MWF, the fraction of signal with T2 between 15 and 40 msec to the entire signal, and GMT2 , the mean T2 on a logarithmic scale from T2 between 40 and 200 msec, were examined in white matter. RESULTS: Intrasite coefficients of variation (COVs) were low (mean 3.99% for MWF and 0.51% for GMT2 ), as were intersite COVs (mean 4.68% for MWF, 0.31% for GMT2 ). Scan-rescan intraclass correlation coefficients (ICCs) (0.76 for MWF and 0.93 for GMT2 ) and Bland-Altman plots indicated good agreement between single site scans. Intersite ICCs were relatively high (0.69 for MWF and 0.92 for GMT2 ), revealing good intersite reliability. CONCLUSION: MWF and GMT2 measures are reproducible between scans and across sites with an equivalent MR scanner and sequence protocol. Multicenter clinical trials using quantitative T2 relaxation are feasible.

Multicenter Measurements of T1 Relaxation and Diffusion Tensor Imaging: Intra and Intersite Reproducibility.

BACKGROUND AND PURPOSE: Quantitative T1 and diffusion tensor imaging (DTI) may provide information about pathological changes underlying disability and progression in diseases like multiple sclerosis (MS). Imaging the corpus callosum (CC), a primary site of damage in MS with a critical role in interhemispheric connectivity, may be useful for assessing overall brain health, prognosis, and therapy efficacy. We assessed the feasibility of multisite clinical trials using advanced MRI by examining the intra and intersite reproducibility of T1 and DTI measurements in the CC and segmented white matter (WM). METHODS: Five healthy volunteers were scanned twice within 24 hours at six 3T sites. Coefficients of variation (COVs) and intraclass correlation coefficients (ICCs) for CC and WM T1 , fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Dax ), and radial diffusivity (Drad ) assessed intrasite and intersite reliability. RESULTS: CC and WM T1 showed excellent intrasite reproducibility with low COVs (mean = .90% and .89%, respectively) and good ICCs (CC = .78, WM = .90). T1 also demonstrated intersite reliability (low COVs: CC = 2.4%, WM = 1.8%; moderate ICCs: CC = .43, WM = .69). DTI had low intrasite COVs (CC: FA = 1.3%, MD = 1.5%, Dax = 1.4%, Drad = 2.2%; WM: FA = .9%, MD = .9%, Dax = .7%, Drad = 1.2%) and high intrasite ICCs (CC: FA = .95, MD = .97, Dax = .94, Drad = .97; CC: FA = .9, MD = .66, Dax = .88, Drad = .63), indicating excellent intrasite reproducibility. DTI also showed excellent intersite reliability with low COVs (CC: FA = 2.1%, MD = 4.1%, Dax = 3.4%, Drad = 5.3%, WM: FA = 1.3%, MD = 1.9%, Dax = 1.8%, Drad = 2.1%,) and good ICCs (CC: FA = .90, MD = .84, Dax = .72, Drad = .90; WM: FA = .83, MD = .34, Dax = .62, Drad = .41). CONCLUSIONS: T1 and DTI measures are reproducible using equivalent MRI scanners and sequence protocols. Using a similar MR system, it is feasible to carry out multicenter studies using T1 and DTI to evaluate changes within the CC and WM.