UCSF

Magnetic resonance imaging (MRI) provides many ways to study human brain anatomy as well as advance our understanding of brain structure, function, and processes that occur with disease. This dissertation project investigated the clinical utility of new and existing MRI techniques to the study of changes that occur in the brains of patients with multiple sclerosis (MS). The new MRI techniques were developed and tested with the goal of attaining more sensitive methods for disease detection than those that are currently available to clinician scientists. These new bioengineering developments included both novel MR acquisition and data analysis techniques for improved non-invasive, quantitative assessments of multiple sclerosis disease processes.

There are many quantitative MRI methods that can be used to detect tissue differences in patient populations when compared to controls. This dissertation research probed the utility of volumetric measurements, T1-relaxation times, and diffusion tensor imaging (DTI) metrics to detection of tissue damage and disease in early stage MS. New DTI methods were developed and new ultra high-field MR hardware and techniques were investigated to examine their potential in identifying previously undetectable brain changes in patients. This bioengineering project included acquiring patient and healthy control data, MRI technique development and optimization, developing and implementing appropriate image-processing methods for parameter measurement, cross-sectional and longitudinal investigations, and determining appropriate statistical approaches for comparative studies.

It was determined that T1-relaxation and DTI measures of mean diffusivity (Dav), fractional anisotropy (FA), and transverse diffusion (EvT) were sensitive enough to detect brain tissue changes at the earliest presentation of disease. Although volume measurements were not different as a group at presentation, atrophy was detectable via volumetry at one-year post baseline. Additionally, DTI measures were able to predict this change, an indication of a causal relationship between microscopic damage and overall tissue loss. The diffusion technique development and high field MRI methods demonstrated the feasibility to collect images with advantages in image quality, signal to noise (SNR), resolution, and ability to detect disease over what was previously available. These developments provide the platform for future work in MRI and its application in MS to better characterize disease.