Diffusion tensor magnetic resonance imaging in the central nervous system.

This thesis begins by describing the effect of diffusion on the nuclear magnetic resonance (NMR) signal, discusses quantitative assessment of diffusion using NMR and introduces the concepts of qualitative and quantitative diffusion imaging in isotropic and anisotropic systems. The first study of subcortical ischaemia using diffusion tensor imaging (DTI) is described and a characteristic pattern of increased diffusivity and reduced diffusion anisotropy in white matter is demonstrated. These findings are highly consistent with post-mortem pathological data, suggesting that DTI can be used to monitor tissue change in vivo and improve understanding of the disease progression. Next, optimal strategies are developed for diffusion measurement in anisotropic systems. Marked improvements in the precision of estimates of diffusion in both phantom and human studies are demonstrated. For example, in a water phantom the standard deviation in the estimate of mean diffusivity is reduced by more than 30% and the artefactual anisotropy is reduced by more than 55% when using the optimal schemes. These improvements have important implications including reduced scan times, improved resolution and increased sensitivity to pathological change. A novel method for displaying the three dimensional orientation of anisotropic structures in one image, and an algorithm for the non-invasive assessment and display of axonal fibre connectivity are then described. Results from healthy human brains are presented demonstrating fibre orientation and connections in the major white-matter tracts. These techniques have important potential applications in the study of a wide range of neurological, psychiatric and developmental disorders. Finally, techniques are described for the characterisation of tissue change in human traumatic brain injury using DTI, and for the detection of cortical spreading depression (CSD) using dynamic diffusion imaging. Static imaging revealed a region of reduced diffusivity and normal T2 bordering the injury site which may represent a reversible state. No candidate CSD events were observed in this initial study.