The Best PhD Thesis in the Faculties of Dentistry, Engineering, Medicine and Science (University of Hong Kong), Li Ka Shing Prize,2009-2010 / published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

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

As compared with other imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI) provides distinctive advantages with better contrast and resolution in imaging brain anatomy and function in vivo. As compared with electrophysiological and histological tracing techniques, MRI enables longitudinal investigation with higher efficiency, lower labor cost and less possibility of sampling error. The major objective of this doctoral work is to utilize cellular and molecular MRI to investigate normal brain functions and injuries in vivo. The results successfully demonstrated MRI as an efficient and sensitive tool for providing comprehensive assessment of brain injuries for promoting accurate prognosis and timely intervention, and for studying fundamental questions with regard to cortical adaptations to challenges in the young adulthood. Firstly, diffusion tensor imaging (DTI) and T2-weighted imaging were employed to characterize longitudinal neuronal and axonal changes of pyramidal tract (PY), a critical part of corticospinal tract, following experimental intracerebral hemorrhage (ICH). Combining DTI with T2-weighted imaging results, ipsilateral PY injuries following ICH were diagnosed as four stages. Quantitative analysis revealed transient diffusivity decreases in PY both contralateral and ipsilateral to the primary hemorrhagic site. Evolution of the ipsilateral DTI parameters correlated with histological findings and indicated evolving and complex pathological processes underlying monotonic FA decrease. These results demonstrated multi-parametric DTI as a valuable imaging tool for non-invasive and longitudinal monitoring of secondary PY injuries. Secondly, DTI and manganese-enhanced MRI (MEMRI) were utilized to detect neuronal changes of substantia nigra (SN) following experimental ICH in rodents. DTI revealed early changes in SN both contralateral and ipsilateral to the primary hemorrhagic site. Evolution of the ipsilateral parameters correlated with the histological results. MEMRI provided insights into the cellular phenotype changes at the late stage. DTI can serve as a valuable imaging tool for non-invasive early detection and longitudinal monitoring of secondary SN injuries, while MEMRI could complementally provide information regarding the late stage inflammation process. Multi-parametric MRI could facilitate clinical and preclinical investigations of SN injuries for exploring disease mechanisms and developing new therapeutic strategies. Thirdly, MEMRI was performed to characterize the interhemispheric interactions in normal and monocularly deprived rodent visual brain. Characteristic transcallosal manganese labeling was observed in the normal group in a manner consistent with previous histological findings. Significant decrease of such labeling was observed in rats with left or right eyelid suturing, or with left eye enucleation, but not in rats with right eye enucleation. These results demonstrated MEMRI as an efficient tool for investigating interhemispheric interactions both anatomically and functionally. These results also indicated that the adult brain recruits different mechanisms for its adaptations to eyelid suturing and enucleation, thus shedding light on our understanding of the transcallosal interhemispheric excitation and inhibition. Lastly, new paradigms other than pressure injection for intracortical manganese administration in MEMRI were introduced to minimize the neuro-toxicity of manganese and maximize the sensitivity of MEMRI for studying cortical functional changes. Transmeningeal diffusion, osmotic pump-based infusion, and intranasal instillation were demonstrated to be successful in tracing interhemispheric connections and detecting stress-related cortical and subcortical changes. / published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

Functional magnetic resonance imaging (fMRI) is a noninvasive technique that can measure blood oxygenation level dependent (BOLD) signal changes in a large field of view with high spatial resolution. The objective of this dissertation is to explore and integrate novel and noninvasive fMRI methods at 7 Tesla to investigate the auditory and visual functions. First, different fMRI methods and stimulation paradigms were employed to explore some basic auditory functions such as sound pressure level (SPL) dependence in different brain structures, and periodotopy and tonotopy in the inferior colliculus (IC). BOLD signal changes increased significantly with SPL and the dependence was monotonic in the IC and lateral lemniscus (LL). The external cortex of IC (ECIC) had higher BOLD signal change than the central nucleus of IC and LL at high SPLs. This study indicates that sparse temporal sampling that is used to reduce the adverse effects of scanner noise may not be a prerequisite in auditory fMRI studies of the IC. Periodotopy and tonotopy in the IC was investigated using continuous imaging with passband balanced steady state free precession (bSSFP) sequence instead of sparse temporal sampling and echo planner imaging (EPI). The spatial gradients of best amplitude modulation frequency (referred to as periodotopy) and characteristic frequency (referred to as tonotopy) varied across the IC, but were approximately perpendicular at different locations. These findings enhance our understanding of how auditory information is preserved in the midbrain. Second, higher order function of behaviorally relevant sounds response selectivity in subcortical structures was investigated. The IC was found to exhibit a stronger response to forward vocalization than to the temporally inverted one. Moreover, blocking cholinergic projections to the IC by atropine injection was observed to significantly reduce the IC response selectivity to the 22 kHz vocalizations. These findings demonstrate the IC response selectivity to vocalizations and suggest that the cholinergic projection contributes to IC responses selectivity to the 22 kHz vocalization. This study provides further understanding about the higher order auditory processing and may have implications for the neural mechanisms underlying human speech perception Third, BOLD fMRI was applied to measure the brain response to stationary and apparent motion visual stimulation. The response of superior colliculus (SC) was weaker under dim light and saturates at higher intensities. Further, the BOLD signal changes and number of activated voxels were both significantly lower during 164 ˚/s apparent motion stimulation compared to stimuli at slower speeds. The results suggest that the SC was more sensitive to slow moving visual stimuli. This is the first fMRI study to investigate motion responsiveness and stimulus speed dependence in the rat SC. Results from these studies complement current knowledge and demonstrate the sophisticated role of subcortical structures such as IC and SC, which may have strong clinical significance to the field of auditory and visual research. Findings from the animal studies should open up new avenues of research and lay the ground work for future human studies. / published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / toc / Medicine / Doctoral / Doctor of Philosophy

No description available.

Dissertation (Ph.D.).--University of Texas Graduate School of Biomedical Sciences at San Antonio, 2007. / Vita. Includes bibliographical references.

<p dir="ltr">Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) via MRI are powerful, noninvasive methods for imaging of the human brain. Here, two studies are presented which explore algorithm development for the processing and analysis of fMRI and DTI-MRI data.</p><p dir="ltr">In the first study, brain functional connectivity was analyzed in a cohort of high school American football athletes over a single play season and compared against participants in non-collision high school sports. Football athletes underwent four resting-state functional magnetic resonance imaging sessions: once before (pre-season), twice during (in-season), and once 34–80 days after the contact activities play season ended (post-season). For each imaging session, functional connectomes (FCs) were computed for each athlete and compared across sessions using a metric reflecting the (self) similarity between two FCs. HAEs were monitored during all practices and games throughout the season using head-mounted sensors. Relative to the pre-season scan session, football athletes exhibited decreased FC self-similarity at the later in-season session, with apparent recovery of self-similarity by the time of the post-season session. In addition, both within and post-season self-similarity was correlated with cumulative exposure to head acceleration events. These results suggest that repetitive exposure to HAEs produces alterations in functional brain connectivity and highlight the necessity of collision-free recovery periods for football athletes.</p><p dir="ltr">In the second study, a method for harmonization of DTI-MRI data across sites was assessed. Pooling of data from multiple sites is limited by noise characteristics of individual scanners and their receive chain elements (e.g., coils, filters, algorithms), requiring careful consideration of methods to harmonize multisite data. Here, the ComBat data harmonization method was assessed on DTI-MRI data to determine if the harmonizing transformation produced by the algorithm could be transferred to harmonize new subject data from previously-observed sites without necessitating reharmonization of pre-existing data. Results indicated that this transferable ComBat methodology (T-ComBat) yielded reduced differences in fractional anisotropy and mean diffusivity across sites when compared with unharmonized data but did not fully reach the performance of ComBat applied to the entire dataset. Results of this study provide guidelines for circumstances (namely, the proportion of subjects one may wish to add to an existing dataset) under which T-ComBat may be effectively applied to harmonize new subject DTI-MRI data.</p>

No description available.

No description available.