Missed radiologic disease activity by conventional side-by-side MRI comparison is associated with future disease activity in multiple sclerosis: Adopting semiautomated coregistration-fusion into clinical practice

Background: Monitoring radiologic disease activity (RDA) is standard of care in multiple sclerosis (MS) because new lesions on magnetic resonance imaging (MRI) are associated with adverse outcomes and frequently prompt treatment reassessment and optimization. Coregistration-fusion comparison (CF) is more sensitive than conventional side-by-side comparison (CS) for detecting new lesions. Objectives: To apply CF to identify CS-missed RDA on brain MRIs originally reported as “stable” and to evaluate whether CS-missed RDA predicts future disease activity. Methods: This retrospective cohort included 314 people with MS (pwMS) with three consecutive brain MRIs: previous MRI (t 1 ), index MRI (t 2 ; reported “stable” on CS), and subsequent MRI (t 3 ). CF was applied to three-dimensional Fluid-Attenuated Inversion Recovery (FLAIR) to identify CS-missed new lesions on t 2 versus t 1 . Future RDA was defined as ⩾1 new lesion on t 3 versus t 2 . Clinical disease activity (CDA) was defined as clinical relapse and/or confirmed disability progression during follow-up after t 2 . Results: CF identified 183 CS-missed new lesions in 65/314 pwMS (20.7%). Future RDA (70.8% vs. 16.1%; p < 0.001) and CDA (20.0% vs. 10.0%; p = 0.028) were more frequent in the CS-missed lesion group. Relapse and disability progression, when analyzed separately, did not differ between groups. CS-missed RDA independently predicted future RDA (adjusted odds ratio (aOR) = 10.43; 95% confidence interval (CI) = 5.31–20.46, p < 0.001) and CDA (aOR = 2.49; 95% CI = 1.10–5.65, p = 0.029). Each additional missed lesion at t 2 was associated with more new lesions at t 3 (incidence rate ratio (IRR) = 1.205; 95% CI = 1.184–1.226, p < 0.001). Conclusion: CF reclassified one in five pwMS reported as “stable” on CS as having CS-missed RDA, which predicted future disease activity.