Increased diffusivity in acute multiple sclerosis lesions predicts risk of black hole

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Abstract
Objective: Diffusion tensor imaging (DTI) quantifies Brownian motion of water within tissue. Inflammation leads to tissue injury, resulting in increased diffusivity and decreased directionality. We hypothesize that DTI can quantify the damage within acute multiple sclerosis (MS) white matter lesions to predict gadolinium (Gd)-enhancing lesions that will persist 12 months later as T1 hypointensities. Methods: A cohort of 22 individuals underwent 7 brain MRI scans over 15 months. DTI parameters were temporally quantified within regions of Gd enhancement. Comparison to the homologous region in the hemisphere contralateral to the Gd-enhancing lesion was also performed to standardize individual lesion DTI parameters. Results: After classifying each Gd-enhancing region as to black hole outcome, radial diffusivity, mean diffusivity, and fractional anisotropy, along with their standardized values, were significantly altered for persistent black holes (PBHs), and remained elevated throughout the study. A Gd-enhancing region with a 40% elevation in radial diffusivity had a 5.4-fold (95% confidence interval [CI]: 2.1, 13.8) increased risk of becoming a PBH, with 70% (95% CI: 51%, 85%) sensitivity and 69% (95% CI: 57%, 80%) specificity. A model of radial diffusivity, with volume and length of Gd enhancement, was associated with a risk of becoming a PBH of 5.0 (95% CI: 2.6, 9.9). Altered DTI parameters displayed a dose relationship to duration of black hole persistence. Conclusions: Elevated radial diffusivity during gadolinium enhancement was associated with increased risk for development of a persistent black hole, a surrogate of severe demyelination and axonal injury. An elevated radial diffusivity within active multiple sclerosis lesions may be indicative of more severe tissue injury.