Background: Diffusely abnormal white matter (DAWM) regions have been found to transform over time into focal white matter lesions (FWML) and to associate with progression in secondary progressive MS (SPMS). However, few studies have assessed changes of DAWM and FWML over time in relapsing-remitting MS (RRMS). Hence, we compared volumetric changes of DAWM and FWML over time as well as the transformation of DAWM into FWML (DAWM-to-FWML) in RRMS and SPMS.
Objectives: 1) To automatically segment FWML and DAWM and characterize the longitudinal evolution of FWML, DAWM and FWML/DAWM Ratio in RRMS vs. SPMS. 2) To compare the volume of DAWM (at each visit) that transforms into FWML in the last MRI scan.
Methods: The data included 4220 MRI scans of 689 SPMS participants, followed for 156 weeks, scanned at screening, weeks 24, 48, 72, 96, 108, and 156; and 2677 scans of 686 RRMS participants, followed for 96 weeks, scanned at screening, weeks 24, 48 and 96. FWML and DAWM were automatically segmented using a previously-validated, automated, 2-weighted-intensity thresholding technique. DAWM voxels at screening, weeks 24, 48, 72, 96, and 108 that transformed into FWML at the last MRI scan (w96 for RRMS, and w156 for SPMS) were identified.
Results: Over time, SPMS participants showed volumes of FWML that significantly increased (t=2.5; p=0.01) along with a significant decrease of DAWM (t=-4.1; p<0.0001), and a significant Ratio increase (t=10.5; p<0.00001). RRMS participants only showed a significant increase in the Ratio (t=6.9; p<0.00001). Interestingly, the voxels of DAWM that transformed into FWML at the last visit significantly changed as disease duration progressed in both RRMS and SPMS, but in different directions, increasing in RRMS (t=3.8; p<0.001) and decreasing in SPMS (t=-12.2; p<0.00001).
Conclusions: A significant volume of DAWM transformed into FWML over time in both RR and SPMS. However, the volume of DAWM that experienced this transformation increased over time in RRMS, explaining why we do not see significant changes of the overall DAWM volumes at each visit. Conversely, the volume of DAWM-to-FWML transformation decreases progressively at each visit in SPMS, reflecting a decrease in the remaining portion of DAWM still available to transform into FWML. The finding that the transformation of DAWM-to-FWML accelerates with time in RRMS, but decelerates in SPMS, could suggest differences in the mechanisms underlying this transformation in RR and SPMS.