Advanced Diffusion MRI Techniques: Methodological Development and Clinical Application

Abstract

Diffusion magnetic resonance imaging (dMRI) has become a mainstay for better understanding the structure of the normal human brain, as well as for understanding the changes that occur in disease. Using the motion of water as a probe for the microscopic environment of tissues, dMRI provides insight into the structure and organization of the brain. Diffusion tensor imaging (DTI), a dMRI provided the neuroimaging community with a means of further characterizing the microstructure of the brain. Further, the macroscopic structure of the brain can be characterized by means of tractography using DTI. While DTI provides a wealth of valuable information, measures of anisotropy and diffusivity derived from DTI are often obscured by partial volume effects and complex neuronal fiber geometries. DTI further assumes that diffusion is Gaussian, which is not the case in the presence of barriers to diffusion, such as cell membranes and the extracellular matrix, resulting in small errors and a diffusion time-dependence to the measures of anisotropy and diffusivity. More advanced frameworks for diffusion imaging, including mean apparent propagator- (MAP) MRI, and constrained spherical deconvolution (CSD) are capable of both resolving complex crossing fiber architectures, as well as better characterizing the true, nongaussian nature of diffusion in tissue. In the following work, DTI, MAP-MRI, and CSD are applied to cerebral palsy (CP) and carotid artery disease (CAD) in order to better characterize the effects of intervention in children with CP and adults with CAD. In the children with CP, we find that there are general structural changes in the corticospinal tracts following 36 weeks of physical therapy, as well as a correlation between the gross motor function measure (GMFM) and both FA and RD that may be trending towards significance. In subjects with CAD, we find that 6 months following carotid endarcterectomy, a surgical procedure to remove the accumulated atherosclerotic placque from the lining of the carotid artery, there are significant increases in the apparent fiber density and structural connectivity largely in the ipsilateral hemisphere of the occluded artery. These works are preliminary, and require the inclusion of more subjects before any major conlusions are drawn, but the results are compelling nonetheless.