Investigations in magnetic resonance diffusion tensor imaging applied to clinical and research medicine

There has been increasing interest in recent years regarding the application of diffusion tensor imaging (DTI) methods to clinical medicine and basic science research. DTI methods are increasingly used to determine the characteristics of individual white matter tracts. These findings include tract-specific diffusion anisotropy thought to result from pathological disease processes as well as the detailed paths of individual tracts as calculated by DTI tractography. However, there has been a need for these tract-specific claims to be systematically investigated for systematic error known to occur as a result of MRI voxel downsampling of brain tissue.;This study uses several approaches to investigate the application of DTI to white matter analyses. First, simulated and in vivo DTI data were analyzed to determine the variability of and systematic error present in region-of-interest (ROI) and fiber tractography analyses of white matter tracts. Significant variability in ROI and tractography results and systematic bias was found to be present in tract-specific analyses, and these findings offer insight into the interpretation of clinical and research DTI findings.;Second, a comparison of fiber tractography methodologies was performed to determine the ability of tractography algorithms to overcome the inherent sampling bias present in DTI acquisitions. To date no systematic analysis of the robustness and reliability of such methods has been performed, and this study suggests that recently developed probabilistic methods may be superior to those commonly used for clinical neurosurgical planning and other applications.;Third, an alternative tract-specific method was used in the analysis of DTI data from a population of type 1 diabetes patients. This method overcomes much of the error that results from voxel downsamping. Groupwise DTI deficits were observed in the type 1 diabetes population, and these deficits were correlated with differences in cortical thickness and neurocognitive test performance.;This study concludes with a DTI analysis of myotonic dystrophy populations. A regional, "holistic" approach was used in this study to observe regional and global white matter anisotropy in contrast to the more error-prone tract-based analyses. Groupwise DTI deficits were observed in type 1 and type 2 myotonic dystrophy patients, and these findings were correlated with gray matter volumetric reductions and reduced facial muscle size.;To conclude, the results from this study suggest that significant and systematic error may be present in DTI studies and that this systematic error should be considered when interpreting DTI findings for clinical and research studies. Furthermore, two alternative analysis approaches are presented that reduce the effects of sampling error and are applied to clinical disease populations.