Brain charts for people living with multiple sclerosis

Multiple sclerosis (MS) is associated with brain volume loss throughout the disease course. Currently available automated segmentation methods can measure total brain volume as well as ventricular volume, which has been advocated as a robust surrogate for brain volume based on clinically acquired magnetic resonance imaging (MRI). However, brain and ventricle volumes change naturally with age and may be susceptible to biases from differences in acquisition hardware, imaging protocol, and image quality, in addition to statistical biases such as regression to the mean. In this work, brain charts for people living with MS were established that account for patient biological sex, age, and differences in acquisition and image quality. 379 subjects were imaged longitudinally at 5 MS centers using 13 MRI scanner models from 2 scanner manufacturers employing a variety of protocols that included T1-weighted and T2-weighted FLAIR imaging. Generalized Additive Models for Location Scale and Shape (GAMLSS) were employed, and scanner metadata as well as automated assessments of image quality were modeled. Cross-sectional brain charts and conditional, longitudinal brain charts were estimated separately in female and male participants resulting in interpretable and intuitive centile estimates. These findings indicate that brain charts for people living with MS are a promising method for turning quantitative volumetrics into actionable knowledge about a patient’s disease. ### Competing Interest Statement AK, KML, and DP are employees of Octave Bioscience. AAB receives consulting income from Octave Bioscience, holds equity in Centile Bioscience, and is a member of the board of directors of Centile Bioscience. Additionally, Octave Bioscience has filed an application for a patent related to this work (PCT/US2023/076710)