Establishment of animal model for studying treatment efficacy of low-intensity pulsed ultrasound stimulations for accelerating bone-tendon repair. Standard partial patellectomy was conducted in the 18-week old rabbits that were then divided into the LIPUS treatment and control groups. The animals were followed for 2, 4, 8, and 16 weeks for various tissue analyses. LIPUS was applied to the experimental animals from postoperative day 3 to 16 weeks. We demonstrated that the healing process of PPT junction was initiated through endochondral ossification. The results showed that the size and length of newly formed bone, and its bone mineral content (BMC), but not its bone mineral density (BMD) were correlated with the failure load, ultimate strength and energy at failure. Using radiographic, biomechanical, histomorphologic and biomechanical methods, it was found that LIPUS had significant accelerating effect on PPT junction repair. We validated our study hypothesis in that LIPUS enhances bone-tendon junction healing by stimulating angiogenesis, chondrogenesis and osteogenesis. / Establishment of in vitro model for mechanism study on effects of low-intensity pulsed ultrasound stimulations. An in vitro model of osteoblast-like cell line (SaOS-2 cells) was studied using cDNA microarray to explore the molecular mechanism mediated by LIPUS. This microarray analysis revealed a total of 165 genes that were regulated at 4 and 24 hours by LIPUS treatment in osteoblastic-like cells. These genes belonged to more than ten protein families based on their function and were involved in some signal transduction pathways. This study has validated the hypothesis that LIPUS can regulate a number of critical genes transient expressions in osteoblast cell line Saos-2. / Keywords. partial patellectomy model; bone-tendon junction repair; low intensity pulsed ultrasound stimulations (LIPUS); gene expression; complementary DNA microarray; rabbit. / This study explored the intact morphology, regular healing and the augmented healing under the effects of low intensity pulsed ultrasound stimulations (LIPUS) on the patella-patella tendon (PPT) junction in a rabbit partial patellectomy model. To probe its possible mechanism, the key genes involved in regulating osteogenesis mediated by LIPUS were identified using the state-of-the-art methods---complementary DNA microarray. / Lu Hongbin. / "June 2006." / Advisers: Ling Qin; Kwok Sui Leung. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1548. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 259-288). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Treatment of brain diseases remains extremely challenging partly due to the fact that critical drug delivery is hindered by the blood-brain barrier (BBB), a specialized and highly selective barrier lining the brain vasculature. Focused ultrasound (FUS), combined with systematically administered microbubbles (MBs), has been established as a technique to noninvasively, locally, and transiently open the BBB. The primary mechanism for temporarily opening the BBB using FUS is microbubble cavitation, a phenomenon that occurs when the circulating microbubbles interact with the FUS beam in the brain vasculature. Over the past two decades, many preclinical and clinical applications of FUS-induced BBB opening have been developed, but certain challenges, such as drug delivery route, cavitation control, inflammation onset, and overall accessibility of the technology, have affected its efficient translation to the clinic. This dissertation focuses on optimizing three aspects of FUS-induced BBB opening for therapeutic applications. The first specific aim investigated FUS-induced BBB opening for drug delivery through the intranasal route. Optimal sonication parameters were determined and applied to FUS-enhanced intranasal delivery of neurotrophic factors in a Parkinson’s Disease mouse model. In the second specific aim, cavitation levels affecting the inflammatory response due to BBB opening with FUS were optimized. The relationship between cavitation during FUS-induced BBB opening and the local inflammation was examined, and a cavitation-based controller system was developed to modulate the inflammatory response. In the third specific aim, the devices used for FUS-induced BBB opening were streamlined. A conventional system for FUS-induced BBB opening includes two transducers: one for therapy and another for cavitation monitoring (single element) or imaging (multi-element). In this aim, a single linear array transducer capable of synchronous BBB opening and cavitation imaging was developed, creating a cost-effective and highly accessible “theranostic ultrasound” device. The feasibility of theranostic ultrasound (TUS) was demonstrated in vivo in both mice and non-human primates. In summary, the findings and methodologies in this dissertation optimized FUS-enhanced intranasal delivery across the BBB, developed a cavitation-controlled system to modulate inflammation in the brain, which has been advantageous in reducing pathology and designed a new system for theranostic ultrasound for drug delivery to the brain. Taken altogether, this thesis contributes to the efficient advancement and optimization of FUS-induced BBB opening technology, thus enhancing its clinical adoption in the fight to treat many challenging brain diseases.

Elastography, which is based on applying pressure and estimating the resulting deformation, involves the forward problem to obtain the strain distributions and inverse problem to construct the elastic distributions consistent with the obtained strains on observation points. This thesis focuses on the former problem whose solution is used as an input to the latter problem. The aim is to provide the inverse problem community with accurate strain estimates of a coronary artery vessel wall. In doing so, a new ultrasonic image-based elastography approach is developed. Because the accuracy and quality of the estimated strain fields depend on the resolution level of the ultrasound image and to date best resolution levels obtained in the literature are not enough to clearly see all boundaries of the artery, one of the main goals is to acquire high-resolution coronary vessel wall ultrasound images at different pressures. For this purpose, first an experimental setup is designed to collect radio frequency (RF) signals, and then image formation algorithm is developed to obtain ultrasound images from the collected signals. To segment the noisy ultrasound images formed, a geodesic active contour-based segmentation algorithm with a novel stopping function that includes local phase of the image is developed. Then, region-based information is added to make the segmentation more robust to noise. Finally, elliptical deformable template is applied so that a priori information regarding the shape of the arteries could be taken into account, resulting in more stable and accurate results. The use of this template also implicitly provides boundary point correspondences from which high-resolution, size-independent, non-rigid and local strain fields of the coronary vessel wall are obtained.