Thesis (Ph. D.)--University of Hong Kong, 2008. / Includes bibliographical references. Also available in print.

Thesis (Ph. D.)--University of Canterbury, 2007. / Typescript (photocopy). Includes bibliographical references (leaves 153-172). Also available via the World Wide Web.

Thesis supervisor: Vincent A. Magnotta. Includes bibliographic references (p. 93-101).

published_or_final_version / Diagnostic Radiology / Master / Master of Philosophy

Magnetic resonance imaging (MRI) is a valuable imaging technique. It provides excellent soft tissue contrast and multi-parametric non-invasive imaging protocols. Among those various techniques, diffusion MRI measures the water diffusion properties of biological tissue. It is a useful tool in characterizing various brain tissue microstructures quantitatively. With its rapid development, it is emerging that subtle changes can be probed by diffusion tensor imaging (DTI) quantitation. The objectives of this doctoral work are to access the subtle microstructural alterations in rodent brains due to hemodynamic changes, fear conditioning and sleep deprivation using in vivo DTI. With the improved reproducibility and specificity achieved by using advanced post-processing and animal preparation procedures, in vivo DTI is expected to be useful to explore the underlying biological mechanisms for posttraumatic stress disorder and memory deficit following sleep loss in human. Firstly, as DTI could be influenced by the presence of water molecules in brain vasculature, for better understand the reproducibility and sensitivity of in vivo DTI measurements, conventional DTI protocol was applied to a well-controlled rat model of hypercapnia. Our data demonstrated that diffusivities increased in whole brain, gray and white matter regions in response to hypercapnia. These results indicate that in vivo DTI quantitation in brain can be interfered by vascular factors on the order of few percents. Cautions should be taken in designing and interpreting quantitative DTI studies as all DTI indices can be potentially confounded by physiologic conditions, cerebrovascular and hemodynamic characteristics. Secondly, recent DTI studies have shown detection of long-term neural plasticity weeks to months following relatively extensive periods of training in animals. However, rapid plasticity within a short period (24 hours) after learning is important for observing the time course of training-evoked changes and narrow down candidate mechanisms. Fear conditioning (FC), which typically occurs over a short timescale (in minutes), was selected as a paradigm for investigation. Using voxel-wise repeated measures analysis, FA was found to increase in amygdala and decrease in hippocampus 1-hour post-FC, and it reversed in both regions 1-day post-FC. Results indicate that DTI can detect rapid microstructural changes in brain regions known to mediate fear conditioning in vivo. DTI indices could be explored as a translational tool to capture potential early biological changes in individuals at risk for developing post-traumatic stress disorder. Thirdly, in vivo DTI was employed to access regional specific microstructural changes following rapid eye movement sleep deprivation (SD), and explore possible temporal differentiation of these changes. With voxel-base analysis, MD is found to decrease in post-SD time points in bilateral hippocampi and cerebral cortex. The distributions of these clusters exhibited differentiable layer specific patterns, which were pointing to dentate gyrus and CA1 layer in hippocampus, and parietal cortex and barrel field layers in cerebral cortex. Results indicate that in vivo DTI is capable to detect microstructural changes in specific layers and reveal temporal distinction between them. These specific layers are possibly more susceptible to sleep loss, and the temporal distinction of changes between these layers might underlie learning and memory decline after SD. / published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

Thesis (M. Phil.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 66-73) Also available in print.

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 97-111). Also available in print.

While diffusion MRI promises an insight into white matter microstructure in vivo, the axonal pathways that connect different brain regions together can only partially be segmented using current methods. Here we present a novel method for estimating the tissue composition of each voxel in the brain from diffusion MRI data, thereby providing a foundation for computing the volume of different pathways in both health and disease. With the tissue dependent diffusion model described in this thesis, white matter is segmented by removing the ambiguity caused by the isotropic partial volumes: both grey matter and cerebrospinal fluid. Apart from the volume fractions of all three tissue types, we also obtain estimates of fibre orientations for tractography as well as diffusivity and anisotropy parameters which serve as proxy indices of pathway coherence. We assume Gaussian diffusion of water molecules for each tissue type. The resulting three-tensor model comprises one anisotropic (white matter) compartment modelled by a cylindrical tensor and two isotropic compartments (grey matter and cerebrospinal fluid). We model the measurement noise using a Rice distribution. Markov chain Monte Carlo sampling techniques are used to estimate posterior distributions over the model’s parameters. In particular, we employ a Metropolis Hastings sampler with a custom burn-in and proposal adaptation to ensure good mixing and efficient exploration of the high-probability region. This way we obtain not only point estimates of quantities of interest, but also a measure of their uncertainty (posterior variance). The model is evaluated on synthetic data and brain images: we observe that the volume maps produced with our method show plausible and well delineated structures for all three tissue types. Estimated white matter fibre orientations also agree with known anatomy and align well with those obtained using current methods. Importantly, we are able to disambiguate the volume and anisotropy information thus alleviating partial volume effects and providing measures superior to the currently ubiquitous fractional anisotropy. These improved measures are then applied to study brain differences in a cohort of healthy volunteers aged 25-65 years. Lastly, we explore the possibility of using prior knowledge of the spatial variability of our parameters in the brain to further improve the estimation by pooling information among neighbouring voxels.

published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy