High b-value Diffusion MRI for Characterizing White Matter Damage

Diffusion magnetic resonance imaging has been widely used to study white matter diseases due to the ubiquity and its non-invasive nature. Amyotrophic lateral sclerosis (ALS), characterized with white matter track damage, is a progressive motor neuron disease in brain and spinal cord with an unknown etiology. Most of diffusion MRI studies focused on altered water diffusion properties in white mater. Nevertheless, the white matter damage might be reflected by the changes of myelin diffusion behaviors that are highly critical, but rarely studied. This thesis aims to characterize white matter damage in a murine model of ALS by analyzing the diffusion properties of myelin using ultra high b-value diffusion MRI. All MRI measurements were performed using a 9.4 T MRI scanner (Agilent, Santa Clara, CA). Stimulated echo acquisition mode sequence was employed with diffusion gradients applied in parallel and perpendicular to the long axis of spinal cord of symptomatic G93A-SOD1 and wild type animal groups respectively. Fast spin echo sequence was employed for anatomical images (T2 weighted). Three diffusion models, bi-exponential, continuous-time random walk (CTRW) model and bi-component model combining CTRW and mono-exponential models were used to analyze the data. Axonal fiber morphology and integrity of the spinal cords were validated by histological analysis. We found differences of signal intensities at lumbar level between diseased and control animals and diffusion-weighted signal decay varied with the diffusion weighting direction relative to spinal nerve fiber orientation on high b-value diffusion-weighted images. Additionally, we found the bi-component model demonstrated the best fit among the three models. In summary, this work has demonstrated the feasibility of diffusion MRI at high b values to evaluate spinal cord alterations in a symptomatic mouse model of ALS. In addition, high b-value diffusion MRI has potential to evaluate spinal cord alterations in other diseases associated with white matter damage.