Regional brain atrophy is a sensitive disability marker for MS patients. A previous study has shown that atrophy of the corpus callosum is an early marker for disease progression. However, the relationship between diffuse pathology in specific brain regions and the course of regional atrophy development remains poorly understood.
To investigate quantitative T1 maps and entropy (amount of T1 inhomogeneity) in regional brain structures from diagnostic MRI (performed at disease onset) of MS patients and compare these findings with healthy controls (HC).
Fifty MS patients and 102 HC were examined on a 3T MRI scanner (MAGNETOM Skyra, Siemens Healthcare, Erlangen, Germany). The MRI protocol comprised 3D MP2RAGE, 3D MPRAGE, 3D FLAIR and 3D DIR. The calculation of T1 maps, brain structure segmentations and brain volume measurements were obtained from a single MP2RAGE scan. Lesion segmentation masks were obtained using the LeManPV prototype software (Siemens Healthcare, Erlangen, Germany). We evaluated T1 maps from normal-appearing white matter (excluding lesions) in the corpus callosum, the brain lobes, brainstem and cerebellum, as well as from normal-appearing gray matter (excluding lesions) in the thalami, basal ganglia, and cortical gray matter. We calculated median regional T1 relaxation times, T1 entropy and volume for the above-mentioned structures for the early-MS group and 50 age- and sex-matched HC subjects. Statistical comparison was performed using t-tests.
The median T1 of the corpus callosum in the early MS group was 838 ms (SD 38.5), with entropy 8.42 (SD 0.24); compared to 810 ms (SD 25.2) and 8.23 (SD 0.13) in the HC group. Statistically significant differences were found in T1 times and entropy between the groups (p<0.001); volumes were, however, not statistically different. Smaller but also statistically significant differences in T1 maps and entropy were found for white matter of the brain lobes (p<0.001). Thalami volumes showed statistically significant differences between groups, but not median T1 times (MS group 1055 ms, SD 32.6 vs. HC 1049 ms, SD 21.2).
Pathology of the normal-appearing white matter in T1 relaxometry can already be detected at MS disease onset. In particular, corpus callosum T1 times were considerably higher at clinical onset of MS compared to HC. We hypothesize that early microstructural changes detected at disease onset lead to evolution of regional brain atrophy.