White matter (WM) lesions with a distinct lesion-tissue contrast are the main radiological hallmark of multiple sclerosis (MS) in standard magnetic resonance imaging (MRI). Pathological WM changes beyond lesion development lack suitable contrasts, rendering the investigation of normal appearing WM (NAWM) more challenging. In this study, repeat quantitative MRI (qMRI) was collected in 9 relapsing remitting MS patients with mild disease over nine months. The relaxation times T1 and T2, the proton density (PD), and the magnetization transfer ratio (MTR) were analysed in the NAWM. For each parameter, both the mean value and the standard deviation were determined across large NAWM regions. The resulting 8-dimensional multi-parameter space includes parameter non-uniformities as additional descriptors of NAWM inhomogeneity. The goals of the study were to investigate (1) which of the eight parameters differ significantly between NAWM and normal WM, (2) if parameter time courses differ between patients with and without radiological disease activity, and (3) if a suitable biomarker can be derived from the multi-parameter space, allowing for NAWM characterization and differentiation from controls. On a group level, all parameters investigated except mean T1 values were significantly affected in MS NAWM. Group classification accuracy using a multi-parametric support vector machine approach in NAWM was 66.7 %. In addition, mean T2 values increased significantly with time for patients with radiological disease activity, but not for patients without radiological activity. In conclusion, our data demonstrate the potential of qMRI for investigating MS pathology in NAWM. T2 measurements in NAWM may enable monitoring of disease activity outside of overt lesions.

BackgroundHistological evidence suggests that pathology in Parkinson's disease (PD) goes beyond nigrostriatal degeneration and also affects the cerebral cortex. Quantitative MRI (qMRI) techniques allow the assessment of changes in brain tissue composition. However, the development and pattern of disease-related cortical changes have not yet been demonstrated in PD with qMRI methods. The aim of this study was to investigate longitudinal cortical microstructural changes in PD with quantitative T1 relaxometry.Methods13 patients with mild to moderate PD and 20 matched healthy subjects underwent high resolution T1 mapping at two time points with an interval of 6.4 years (healthy subjects: 6.5 years). Data from two healthy subjects had to be excluded due to MRI artifacts. Surface-based analysis of cortical T1 values was performed with the FreeSurfer toolbox.ResultsIn PD patients, a widespread decrease of cortical T1 was detected during follow-up which affected large parts of the temporo-parietal and occipital cortices and also frontal areas. In contrast, age-related T1 decrease in the healthy control group was much less pronounced and only found in lateral frontal, parietal and temporal areas. Average cortical T1 values did not differ between the groups at baseline (p = 0.17), but were reduced in patients at follow-up (p = 0.0004). Annualized relative changes of cortical T1 were higher in patients vs. healthy subjects (patients: − 0.72 ± 0.64%/year; healthy subjects: − 0.17 ± 0.41%/year, p = 0.007).ConclusionsIn patients with PD, the development of widespread changes in cortical microstructure was observed as reflected by a reduction of cortical T1. The pattern of T1 decrease in PD patients exceeded the normal T1 decrease as found in physiological aging and showed considerable overlap with the pattern of cortical thinning demonstrated in previous PD studies. Therefore, cortical T1 might be a promising additional imaging marker for future longitudinal PD studies. The biological mechanisms underlying cortical T1 reductions remain to be further elucidated.

Out of the parameters studied, cortical T is best suited to detect cortical damage as an imaging surrogate of clinical disability in RRMS. J. Magn. Reson. Imaging 2016;44:1600-1607.

T2 relaxation time is a quantitative MRI in vivo surrogate of cerebral tissue damage in multiple sclerosis (MS) patients. Cortical T2 prolongation is a known feature in later disease stages, but has not been demonstrated in the cortical normal appearing gray matter (NAGM) in early MS. This study centers on the quantitative evaluation of the tissue parameter T2 in cortical NAGM in a collective of early MS and clinically isolated syndrome (CIS) patients, hypothesizing that T2 prolongation is already present at early disease stages and variable over space, in line with global and focal inflammatory processes in MS. Additionally, magnetization transfer ratio (MTR) mapping was performed for further characterization of the expected cortical T2 alteration. Quantitative T2 and MTR maps were acquired from 12 patients with CIS and early MS, and 12 matched healthy controls. The lesion-free part of the cortical volume was identified, and the mean T2 and MTR values and their standard deviations within the cortical volume were determined. For evaluation of spatial specificity, cortical lobar subregions were tested separately for differences of mean T2 and T2 standard deviation. We detected significantly prolonged T2 in cortical NAGM in patients. T2 prolongation was found across the whole cerebral cortex and in all individual lobar subregions. Significantly higher standard deviations across the respective region of interest were found for the whole cerebral cortex and all subregions, suggesting the occurrence of spatially inhomogeneous cortical damage in all regions studied. A trend was observed for MTR reduction and increased MTR variability across the whole cortex in the MS group, suggesting demyelination. In conclusion, our results suggest that cortical damage in early MS is evidenced by spatially inhomogeneous T2 prolongation which goes beyond demyelination. Iron deposition, which is known to decrease T2, seems less prominent.

• T1 mapping is sensitive to age-related microstructural changes in a longitudinal setting. • T1 decreases were predominantly localized in the lateral frontal, parietal and temporal cortex. • The rate of T1 reduction was more prominent in subjects with higher age. • These changes most likely reflect decreasing cortical water and increasing iron concentrations.