Diffusion Magnetic Resonance Imaging Tractography of the Fornix in Pediatric and Adult Multiple Sclerosis
Creators: Weber, Carly
Publisher: name: University of Alberta Library
Year: 2024

<p>The fornix is the main white matter output tract of the hippocampus and part of the limbic system, which is involved in aspects of memory and cognition. High-resolution, fluid-suppressed diffusion tensor imaging tractography has identified marked volume and diffusion abnormalities of the fornix in adults with multiple sclerosis (MS), with greater fornix changes in those with cognitive impairment. Fornix microstructural changes have also been identified across the healthy lifespan and across limited age ranges of disease cohorts, including MS, using lower resolution diffusion tensor imaging tractography without fluid-suppression, which is not ideal for measuring the fornix. Therefore, the objectives of this thesis were to use high-resolution, fluid-suppressed diffusion tractography to (i) determine if the fornix is affected in child/adolescent pediatric-onset MS using the same imaging protocols used to study the fornix in adults with MS, which would suggest its early involvement in the disease course, and (ii) analyze fornix microstructure changes across the MS lifespan, compared to healthy controls.</p>

<p>High-resolution, fluid-suppressed diffusion tractography was used to identify the fornix in 42 MS patients (13-63 years old), including 11 pediatric-onset MS (19 years of age), and 103 healthy controls (12-65 years). First, fornix volume and diffusion metrics were compared between the 11 pediatric-onset MS patients and 26 age/sex matched controls, as well as total/regional brain volumes, and correlated with cognitive/clinical scores (Chapter 3). Fornix volume/diffusion metrics and total/regional brain volumes of all 42 MS patients were then compared to all 103 healthy controls across age (Chapter 4). </p>

<p>Chapter 3 results showed that relative to controls, pediatric-onset MS patients had significantly smaller fornix (-26%), which was greater than other proportional losses in total/regional brain volumes. Notably, hippocampus volume was not significantly lower in pediatric-onset MS. Fornix diffusion tensor imaging metrics yielded significantly lower fractional anisotropy (-7%), as well as higher mean (12%), axial (7%), and radial (16%) diffusivities in pediatric-onset MS. There were no significant correlations between fornix volume/diffusion metrics and cognitive/clinical scores. Fornix volume/diffusion metrics in pediatric-onset MS were similarly affected relative to controls as in our lab’s  previous adult MS study, and showed marked injury to the fornix that precedes injury to connected gray matter such as the hippocampus, implicating the fornix as an early brain region affected in MS, possibly by demyelination as indicating by the largest diffusion metric change in radial diffusivity. </p>

<p>Chapter 4 results showed that control fornix volume increased until 33 years and then declined, fractional anisotropy showed no age relationship, and mean, axial and radial diffusivities decreased until 33, 30, and 32 years, respectively, and then increased with age. MS fornix volume and fractional anisotropy followed similar trends as controls across age, but remained below controls at all ages, and mean, axial and radial diffusivities did not show age relationships but remained above controls at all ages, especially fornix volume and radial diffusivity. Presumably, pathological effects on fornix diffusion metrics overwhelmed expected age relationships in MS, and showed deviations from controls indicative of MS injury across all ages, suggesting the fornix is an early and consistent target of injury in MS, and that fornix injury is not progressive in MS.</p>

<p>These findings implicate the fornix as an early brain region affected in MS and may be largely related to its location within cerebrospinal fluid, which may contain MS inflammatory factors early on in the disease course. </p>