Dynamic Expansion and Contraction of Multiple Sclerosis T2-weighted Hyperintense Lesions are Present Below the Threshold of Visual Perception.

Background and purpose: The study of T2-weighted hyperintense lesions resulting from autoimmune inflammatory injury and associated volumes within the CNS remains fundamental to the diagnosis and disease surveillance of multiple sclerosis (MS). We investigated the dynamic changes of individual T2-weighted hyperintense MS lesions on MRI and hypothesized that variations may be present below the threshold of visual perception when evaluating longitudinal data.

Materials and methods: A retrospective study was performed of people with MS, incorporating data from three consecutive MRI time points acquired within a single academic center. All included MRI studies lacked formal imaging interpretations of newly enlarging or contracting T2-weighted hyperintensities. Well defined, non-coalescing, individual T2-weighted hyperintense lesions were targeted. A total of 8-12 lesions were randomly selected in a blinded fashion at MRI time point 1 and 3-dimensional lesion volumes followed over MRI time points 2 and 3. The impact of treatment on lesion expansion and relationship to brain MRI advancement, patient-reported progression of disease, and physician-identified progression was also studied.

Results: The study cohort was comprised of 115 people (81 (70.4%) female; mean disease duration of 6.62 years(y) (standard deviation: 6.68y)) who were primarily White (79.1%). A total of 1,426 focal T2-weighted hyperintense MS lesions were identified on MRI time point 1 and longitudinally followed over MRI time points 2 and 3. In the evaluation of raw changes in individual T2-weighted hyperintense lesion volumes from MRI time point 1 to MRI time point 2, a similar number of individuals were observed with predominantly expanding (49/115; 42.6%) or contracting (51/115; 44.3%) lesions. However, the majority of lesions expanded in volume (48/115; 41.7%) versus those that contracted (45/115; 39.1%) when evaluating MRI time point 3 to time point 1. Those individuals not on active treatment had a 67.15% reduction in the odds of more individual lesions predominantly contracting in volume relative to those on low-efficacy disease modifying therapy treatment (95% CI=[-83.89, -33.01], p=0.0008) and 74.02% reduction for those on high-efficacy treatment (95% CI=[-87.37%,-46.56%], p<0.0001).

Conclusions: Dynamic changes in T2-weighted hyperintense lesions are abundant, occurring below the threshold of visual perception and are present more frequently in untreated individuals.

Abbreviations: MS = multiple sclerosis; DMT = disease modifying therapy; 2D = 2-dimensional; 3D = 3-dimensional; LMS = Lambda, Mu, and Sigma.