Optic Nerve Lesion Volume, White Matter Hyperintensities, and Brain Volumetrics in Multiple Sclerosis: A Multi‐Sequence MRI ‐Based Analysis

Objectives To examine the association between optic nerve lesion volume (ONLV) on double inversion recovery (DIR) MRI and other imaging biomarkers of disease burden in multiple sclerosis (MS), including white matter hyperintensities (WMHs), T1‐weighted hypointensities, and brain volumetrics. The study explores whether ONLV reflects more severe neurodegenerative MS profile. Materials and Methods In this cross‐sectional study, 212 MS patients underwent 3 T MRI, including 3D T1W, FLAIR, and DIR sequences. Optic nerve lesions were segmented on DIR and quantified volumetrically. Patients were categorized by optic nerve involvement: none ( n = 59), unilateral ( n = 60), bilateral ( n = 93). WMHs were analyzed using AI‐based tool. T1W hypointensities and brain volumetrics were extracted using FreeSurfer and AI algorithm applied to 3D T1W and FLAIR images. Multivariate models were adjusted for multiple covariates. Results ONLV positively correlated with periventricular ( r = 0.365, p < 0.001), deep ( r = 0.165, p = 0.005), and juxtacortical ( r = 0.163, p = 0.007) WMHs. Bilateral involvement was associated with higher WMH burden, increased T1W hypointensities ( β = 10.91, p < 0.001). ONLV was associated with greater white matter atrophy ( β = −107.02, p = 0.016); after adjustment for age, this association was attenuated, while bilateral optic nerve involvement emerged as predictor of gray matter atrophy. Periventricular WMHs also correlated with global cortical and subcortical gray matter loss. Conclusions ONLV is associated with greater lesion load and neurodegeneration in MS. Longitudinal studies are needed to confirm prognostic value of ONLV as a candidate biomarker of disease severity.