Conversion of diffusely abnormal white matter to focal lesions is linked to progression in secondary progressive multiple sclerosis

Abstract

Background: Diffusely abnormal white matter (DAWM) regions are observed in magnetic resonance images of secondary progressive multiple sclerosis (SPMS) patients. However, their role in clinical progression is still not established. Objectives: To characterize the longitudinal volumetric and intensity evolution of DAWM and focal white matter lesions (FWML) and assess their associations with clinical outcomes and progression in SPMS. Methods: Data include 589 SPMS participants followed up for 3 years (3951 time points). FWML and DAWM were automatically segmented. Screening DAWM volumes that transformed into FWML at the last visit (DAWM-to-FWML) and normalized T1-weighted intensities (indicating severity of damage) in those voxels were calculated. Results: FWML volume increased and DAWM volume decreased with an increase in disease duration ( p < 0.001). The Expanded Disability Status Scale (EDSS) was positively associated with FWML volumes ( p = 0.002), but not with DAWM. DAWM-to-FWML volume was higher in patients who progressed (2.75 cm3 vs. 1.70 cm3; p < 0.0001). Normalized T1-weighted intensity of DAWM-to-FWML was negatively associated with progression ( p < 0.00001). Conclusion: DAWM transformed into FWML over time, and this transformation was associated with clinical progression. DAWM-to-FWML voxels had greater normalized T1-weighted intensity decrease over time, in keeping with relatively greater tissue damage. Evaluation of DAWM in progressive multiple sclerosis provides a useful measure for therapies aiming to protect this at-risk tissue with the potential to slow progression.

Nonlesional diffusely abnormal appearing white matter in clinically isolated syndrome: Prevalence, association with clinical and MRI features, and risk for conversion to multiple sclerosis

“…3 A 3-year longitudinal study in secondary progressive MS has shown that the development of lesions in DAWM regions is associated with clinical progression. 13 Quantitative MRI measures of DAWM in relapsing remitting, primary progressive and secondary progressive MS demonstrate abnormalities in magnetization transfer ratio, myelin water fraction, fractional anisotropy, mean diffusivity, and T 1 relaxation time, with values of these metrics typically between those of T 2 lesions and NAWM. 7,[9][10][11][12]14,15 DAWM has not been systematically described at the earliest stage of MS, known as clinically isolated syndrome (CIS).…”

BISON: Brain tissue segmentation pipeline using T1‐weighted magnetic resonance images and a random forest classifier

“…51 All segmentations were then visually assessed, and BISON tissue classification results passed quality control for all timepoints. 48 The successful application of BISON in other data sets with different imaging characteristics and underlying pathologies further validates its robustness and domain adaptability.…”

“…In addition to the Human Phantom data set, BISON has also been used to perform tissue classification on other data sets, [48][49][50][51] including data from a multicenter and multiscanner (20 different scanner models from four manufacturers, including both 1.5T and 3T scanners) clinical trial of 589 patients with secondary progressive multiple sclerosis (3951 timepoints), 48 as well as a data set of patients with pediatric-onset acquired demyelinating syndrome. 51 All segmentations were then visually assessed, and BISON tissue classification results passed quality control for all timepoints.…”

“…In fact, we have used BISON to perform tissue classification in approximately 4000 scans of patients with multiple sclerosis and varying levels of WMHs. 48,49 These results suggest that standard image-processing pipelines should not be used for tissue classification without modification in the presence of WMHs.…”

Diffusely abnormal white matter in multiple sclerosis

“…21,22 However, lesions do develop in areas of DAWM, suggesting that DAWM can be an area within which active pathology can arise, which could confound in vivo and postmortem observations. 21,45 The "inside-out hypothesis" of the pathogenesis of…”