Cortical fractal dimension predicts disability worsening in Multiple Sclerosis patients

Abstract

Background: Fractal geometry measures the morphology of the brain and detects CNS damage. We aimed to assess the longitudinal changes on brain's fractal geometry and its predictive value for disease worsening in patients with Multiple Sclerosis (MS).

Methods: We prospectively analyzed 146 consecutive patients with relapsing-remitting MS with up to 5 years of clinical and brain MRI (3 T) assessments. The fractal dimension and lacunarity were calculated for brain regions using box-counting methods. Longitudinal changes were analyzed in mixed-effect models and the risk of disability accumulation were assessed using Cox Proportional Hazard regression analysis.

Results: There was a significant decrease in the fractal dimension and increases of lacunarity in different brain regions over the 5-year follow-up. Lower cortical fractal dimension increased the risk of disability accumulation for the Expanded Disability Status Scale [HR 0.9734, CI 0.8420-0.9125; Harrell C 0.59; Wald p 0.038], 9-hole peg test [HR 0.9734, CI 0.8420-0.9125; Harrell C 0.59; Wald p 0.0083], 2.5% low contrast vision [HR 0.4311, CI 0.2035-0.9133; Harrell C 0.58; Wald p 0.0403], symbol digit modality test [HR 2.215, CI 1.043-4.705; Harrell C 0.65; Wald p 0.0384] and MS Functional Composite-4 [HR 0.55, CI 0.317-0.955; Harrell C 0.59; Wald p 0.0029].

Conclusions: Fractal geometry analysis of brain MRI identified patients at risk of increasing their disability in the next five years.

Keywords: Brain MRI; Clinical outcomes; Disability progression; Fractal dimension; Multiple Sclerosis.