High-resolution Fluid-suppressed Diffusion Tractography Shows Altered Fornix Volume and Diffusion Metrics in Pediatric Multiple Sclerosis

Motivation: It is unknown if the fornix (main output tract of the hippocampus) is affected in pediatric multiple sclerosis (MS), which would suggest its early involvement. Goal(s): Are the volume and diffusion metrics of the fornix affected in pediatric MS as it is in adult MS, and does fornix injury precede damage to the hippocampus?Approach: Fornix diffusion tensor imaging and whole-brain MPRAGE were acquired from pediatric MS patients and controls. The fornix was identified with tractography. Results: Pediatric MS showed a much (29%) smaller fornix with abnormal diffusion metrics indicative of early injury, but had no difference in hippocampus volume, compared to controls. Impact: Diffusion tractography identifies marked injury to the fornix, a small white matter tract important for cognition, in children and adolescents with multiple sclerosis, while the hippocampus volume is unaffected, implicating the fornix as an early brain target in this disease.