Thesis (M. S.)--Bioengineering, Georgia Institute of Technology, 2006. / Dr. Arthur Koblasz, Committee Member ; Dr. John N. Oshinski, Committee Member ; Dr. Paul J. Benkeser, Committee Chair.

Thesis (Ph. D.)-- University of Washington, 2005. / Vita. Includes bibliographical references (leaves 152-164).

M.Tech. (Chiropractic) / The aim of this study is to compare Chiropractic Manipulative Therapy of the lumbar spine combined with Therapeutic Ultrasound Therapy over the adjacent lumbar paraspinal muscles to ascertain the most effective protocol in the treatment of Chronic Mechanical Lower Back Pain. Thirty participants with Chronic Mechanical Lower Back Pain between the ages of 18 and 35 years were recruited. Successful participants were randomly placed in two groups, of fifteen participants each, which would receive different treatment protocols according to their group allocation. Group One received Chiropractic Manipulative Therapy to lumbar spine restrictions. Group Two received Chiropractic Manipulative Therapy to the lumbar spine restrictions as well as Therapeutic Ultrasound Therapy to the adjacent paraspinal muscles. The participants completed a total of seven visits, including 6 treatments over 3 weeks. Subjective and Objective readings were taken on the first, fourth and seventh visits. Subjective readings from each participant were recorded using the Oswestry Disability Iindex and Numerical Pain Rating Scale. Objective readings were taken and recorded three times consecutively using a Pressure Algometer over the adjacent lumbar paraspinal muscles and a Digital Inclinometer to measure lumbar spine range of motions. The statistical data was analysed using the Friedman test, Mann-Whitney test and the Bonferroni test. The results demonstrated overall that both groups responded favourably to their specific treatment protocols, however no significant differences between groups was noted, highlighting the positive effects of the manipulation alone.

Ultrasound is an effective imaging modality because it is safe, unobtrusive and portable. However, it is also very operator-dependent and significant skill is required to capture quality images and properly detect abnormalities. Training is an important part of ultrasound, but the limited availability of training courses presents a significant hindrance to the use of ultrasound being used in additional settings. The goal of this work was to design and implement an interactive training system to help train and evaluate sonographers. The Interactive Training System for Medical Ultrasound is an inexpensive, software-based training system in which the trainee scans a lifelike manikin with a sham transducer containing a 6 degree of freedom tracking sensor. The observed ultrasound image is generated from a pre-stored 3D image volume and is controlled interactively by the sham transducer's position and orientation. Based on the selected 3D volume, the manikin may represent normal anatomy, exhibit a specific trauma or present a given physical condition. The training system provides a realistic scanning experience by providing an interactive real-time display with adjustable image parameters such as scan depth, gain, and time gain compensation. A representative hardware interface has been developed including a lifelike manikin and convincing sham transducers, along with a touch screen user interface. Methods of capturing 3D ultrasound image volumes and stitching together multiple volumes have been evaluated. System performance was analyzed and an initial clinical evaluation was performed. This thesis presents a complete prototype training system with advanced simulation and learning assessment features. The ultrasound training system can provide cost-effective and convenient training of physicians and sonographers. This system is an innovative approach to training and is a powerful tool for training sonographers in recognizing a wide variety of medical conditions.

"Ultrasound phantoms that mimic injury are training devices that can emulate pre- and post-injury conditions within specific regions of human anatomy. They have the potential to be useful tools for teaching medical personnel how to recognize trauma conditions based on ultrasound images. This is particularly important because the increased use of portable ultrasound systems allows earlier diagnosis of internal trauma at locations such as traffic accidents, earthquakes, battlefields and terrorist attacks. A physical injury mimicking ultrasound phantom of the peritoneal cavity was constructed that mimicked the ultrasonic appearance of internal bleeding. Bleeding was simulated by injecting 600 mL of fluid of varying densities into the bulk of the phantom and comparing the ultrasonic appearance to before bleeding was simulated. The physical phantom was used to investigate whether or not the density of the injected fluid had any influence on the increase of inter-organ fluid volumes. The physical phantom was imaged in 3D with a 4.5 MHz phased array transducer, and two fluid volumes were segmented using the segmentation software ITK-SNAP. The 3D image representation of the phantom showed a difference qualitatively and quantitatively between pre-injury and post-injury conditions. Qualitatively, the physical model was analyzed. These specific criteria were analyzed within each image: 1) the number of individual organs that are present, 2) the number of other organs that each individual organ touches, 3) the appearance of fluid between the organs and the scanning membrane and 4) the merging of two separate fluid pockets. Using a Wilcoxon Rank-Sum test, a statistically significant difference was shown to exist between pre-injury and post-injury ultrasound images with a 95% level of confidence. Quantitatively, a Chi-Squared test was used to show that the volume of fluid between adjacent organs, calculated by ITK-SNAP, had no dependence on the density of the injected fluid. Furthermore, using a one-tailed T-test, there was at least a 99.9% confidence that the inter-organ volume estimations for the pre-injury and post-injury configurations were statistically different. As a final means of evaluation, the experimental phantom was taken to Harvard Medical School in November 2006 and analyzed by ultrasonographers. The doctors were very excited about its potential uses and found other interesting characteristics that the phantom was not designed for. In addition to modeling the appearance of an injected fluid volume, visualization of fluid flowing into the phantom, modeling the appearance of air in the inter-peritoneal space and simulating a surgical tool or bandage being accidentally left inside the patient could be modeled as well. The injury mimicking phantom was also modeled numerically, using ADINA finite element software. Using the same external dimensions as the experimental model, the numerical model showed that for physiologically unrealistic, very high fluid injection densities, the displacement of the organs had no statistical dependence on the density of the injected fluid, using an acceptance criterion of: P-value < 0.05. This was confirmed using an F-test of the average organ phantom tip displacement tabulated at several different times during simulation. The P-value obtained for analyzing the average tip displacement was 0.0506. However, a plot of the mass ratio, an expression of how the injected fluid has dispersed into the bulk of the phantom, showed that an unrealistically high fluid injection density had a different mass ratio profile than the other fluid injection densities that were simulated. This F-test revealed a strong indication, P-value = 0.0069, that the very high density caused a different fluid dispersion pattern. The numerical phantom offered a distinct advantage over the experimental model in that the dispersion of the injected fluid could be modeled numerically but not observed experimentally. Modeling the phantom numerically had some disadvantages. The numerical model had to have a large gap between adjacent organs. This had to occur because the contact algorithm within ADINA is incapable of modeling dynamic contact when fluid-structure interactions are modeled. This led to a volume fraction representation of the solid domain that was too low compared with the experimental model and what is found anatomically. For future iterations of the injury mimicking phantom, the numerical model will be used to help design the physical phantoms."

Thesis. 1975. Sc.D.--Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science. / Vita. / Includes bibliographical references. / Sc.D.

Chung, Shu Lu. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 109-118). / Abstracts in English and Chinese. / Abstract --- p.i-iv / 中文摘要 --- p.v-vii / Publications --- p.viii / Acknowledgements --- p.ix / List of Abbreviations --- p.x-xi / Index for Figures --- p.xii-xiv / Index for Tables --- p.xv / Table of Contents --- p.xvi-xix / Chapter Session 1: --- Introduction --- p.1 / Chapter 1.1 --- Biology of fracture healing process --- p.2 / Chapter 1.1.1 --- Stage of inflammation --- p.2-3 / Chapter 1.1.2 --- Stage of soft callus formation --- p.3-4 / Chapter 1.1.3 --- Stage of hard callus formation --- p.4-5 / Chapter 1.1.4 --- Stage of bone remodeling --- p.5 / Chapter 1.2 --- Conventional treatments and its limitations --- p.5-6 / Chapter 1.3 --- Biological treatments in accelerating fracture healing process --- p.6-7 / Chapter 1.4 --- Biophysical treatments in accelerating fracture healing process --- p.7-8 / Chapter 1.4.1 --- Electromagnetic fields --- p.8-9 / Chapter 1.4.2 --- Shockwave --- p.9 / Chapter 1.4.3 --- Low intensity pulsed ultrasound --- p.9-11 / Chapter 1.5 --- Properties of ultrasound --- p.11 / Chapter 1.5.1 --- Ultrasound signals --- p.11-12 / Chapter 1.5.2 --- Attenuation of ultrasound --- p.12-14 / Chapter 1.5.3 --- Modes of ultrasound wave propagation --- p.14-15 / Chapter 1.5.4 --- Reflection and critical angle --- p.15-18 / Chapter 1.6 --- Insights from previous studies --- p.18-19 / Chapter 1.7 --- Hypothesis --- p.19 / Chapter 1.8 --- Study plan --- p.20 / Chapter 1.9 --- Objectives --- p.20 / Chapter Session 2: --- Materials and Methodology --- p.25 / Chapter 2.1 --- Materials --- p.26 / Chapter 2.2. --- Closed femoral fracture rat model --- p.26 / Chapter 2.2.1 --- Operation procedures --- p.26-27 / Chapter 2.3 --- Groupings --- p.27 / Chapter 2.4 --- Low Iintensity Pulsed Ultrasound treatment --- p.28 / Chapter 2.4.1 --- Incident angles determination --- p.28 / Chapter 2.4.2 --- LIPUS devices --- p.29 / Chapter 2.4.2 --- Set up of standardized platform --- p.29-30 / Chapter 2.4.4 --- Treatment procedure --- p.30 / Chapter 2.5 --- Radiographic analysis --- p.31 / Chapter 2.6 --- Micro-Computed Tomography --- p.32 / Chapter 2.6.1 --- Micro-Computed Tomography scanning --- p.32 / Chapter 2.6.2 --- Micro-Computed Tomography analysis --- p.32-33 / Chapter 2.7 --- Histology --- p.34 / Chapter 2.7.1 --- Sample preparation --- p.34 / Chapter 2.7.2 --- Histomorphometrical analysis --- p.34-35 / Chapter 2.8 --- Mechanical Testing --- p.35 / Chapter 2.9 --- Statistical analysis --- p.35 / Chapter Session 3: --- Results --- p.48 / Chapter 3.1 --- Radiographic analysis --- p.49 / Chapter 3.1.1 --- Qualitative analysis - Callus bridging rate --- p.49 / Chapter 3.1.2 --- Quantitative analysis - Callus area and callus width --- p.49-50 / Chapter 3.2 --- Micro-computed tomography analysis --- p.50 / Chapter 3.2.1 --- Qualitative analysis - 3D reconstructed images --- p.50-51 / Chapter 3.2.2 --- Quantitative analysis - Bone volume of callus --- p.51 / Chapter 3.2.3 --- Quantitative analysis - Bone mineral density and bone mineral content --- p.51-52 / Chapter 3.3 --- Biomechanical test --- p.52-53 / Chapter 3.4 --- Histomorphological analysis --- p.53 / Chapter 3.4.1 --- Qualitative analysis --- p.53 / Chapter 3.4.2 --- Quantitative analysis --- p.53-54 / Chapter Session 4: --- Discussion --- p.85-87 / Chapter 4.1 --- Enhancement effects of LIPUS at different incident angles --- p.88 / Chapter 4.1.1 --- LIPUS transmitted at 350 accelerated the fracture healing process --- p.88 / Chapter 4.1.1.1 --- Callus bridging and callus mineralization --- p.88-89 / Chapter 4.1.1.2 --- Dose dependent effects of LIPUS -Maximization of ultrasound energy --- p.89-90 / Chapter 4.1.2 --- LIPUS transmitted at 35° enhanced the restoration of mechanical properties in fracture healing process --- p.90 / Chapter 4.1.2.1 --- Biomechanical properties --- p.90-91 / Chapter 4.1.2.2 --- Bone mineral density and bone mineral content --- p.91-92 / Chapter 4.1.2.3 --- Highly mineralized callus area and volume --- p.92-93 / Chapter 4.2 --- 35° may be the critical angle for further enhancing fracture healing --- p.93 / Chapter 4.2.1 --- LIPUS transmitted at 35° may be the first critical angle in this study --- p.93-95 / Chapter 4.2.2 --- Effects of different incident angles --- p.95-96 / Chapter 4.3 --- Mechanism of LIPUS at different incident angles on fracture healing process --- p.96 / Chapter 4.3.1 --- Endochondral ossification --- p.96-99 / Chapter 4.4 --- Advantages in using LIPUS transmitted at critical angle --- p.99 / Chapter 4.5 --- Limitations of the study --- p.100 / Chapter 4.5.1 --- Animal model --- p.100 / Chapter 4.5.2 --- Treatment sites of LIPUS transmitted at different incident angles --- p.100 / Chapter 4.5.3 --- Types of fracture --- p.101 / Chapter Session 5: --- Conclusions --- p.102-104 / Chapter Session 6: --- Future Studies --- p.105 / Chapter 6.1 --- Protocol and regime of LIPUS transmitted at different angles --- p.106 / Chapter 6.2 --- Periosteum-stripped fracture model --- p.106-107 / Chapter 6.3 --- Molecular mechanism of LIPUS transmitted at different incident angles --- p.107-108 / Bibliography --- p.109-118 / Appendix I --- p.119

The inability to transport molecules efficiently and easily into cells and across tissues is one of the major limitations of developing drug delivery systems. A novel approach to overcoming this problem could be the use of low-frequency ultrasound to make cell membranes and tissues more permeable. Previous studies show that normally impermeant molecules can be transported into cells exposed to ultrasound; however, the mechanism by which this occurs is not well understood. Our hypothesis is that low frequency ultrasound can reversibly disrupt membrane structure, thus allowing diffusion-driven intracellular delivery of molecules through a breach in the cell membrane. The effects of ultrasound are not limited to uptake of molecules; there can also be significant loss of cell viability after sonication. Therefore, the focus of this work is to determine the mechanisms by which molecular uptake and cell death occur from ultrasound exposure. The long-term goal of this work is to increase the number of viable cells that experience uptake by controlling the effects that cause cell death. Our data have show that large molecules (r ≤ 28 nm) can be taken into cells after exposure to 24 kHz (10% duty cycle for 2 s of exposure time at 0.1 pulse length over a range of pressures) ultrasound and that uptake of these molecules can occur even after sonication ended. In experiments developed to isolate the mechanism(s) of uptake, DU145 prostate cancer cells depleted of ATP energy and intracellular calcium showed no uptake of calcein, a small fluorescent molecule (MW = 623 Da), nor did sonicated lipid bilayers (red blood cell ghosts), suggesting that uptake is calcium mediated and requires active mechanisms in viable cells. Multiple types of microscopy, including electron and laser scanning confocal, showed evidence of large plasma membrane disruptions which support the hypothesis that transport of molecules into cells occurs through repairing wounds. Microscopy studies also indicated that much if the sonication-mediated death can occur by instantaneous cellular lysing and rapid cell death (within minutes post-exposure) due to wound-instigated necrosis; in addition, characteristics of rapidly induced controlled death modes were seen and found to be non-caspase-mediated within an hour after sonication ended.

When human mesenchymal stem cells (hMSCs) are cultured inside a 3D collagen meshwork, they become a potential tissue engineering bone graft alternative. However, the in vitro osteogenesis rate of hMSCs is slow, leading to a low mineral deposition. To enhance the osteogenic differentiation of hMSCs, low intensity pulsed ultrasound (LIPUS) was employed as an external stumulus. The present study demonstrated the feasibility of employing daily LIPUS exposure for enhancing osteogenesis in vitro. Exposure of seven consecutive days LIPUS, each of 30 minutes duration, did not affect the cell viability, and the organization of hMSCs within the collagen meshwork was not disturbed. The calcium deposition within the collagen meshwork was enhanced after seven days of exposure. The osteoinductivity was also upregulated at the early period of culture. In order to optimizing the enhancement effects of LIPUS, various ultrasound parameters, including intensity, exposure duration and exposure repetition were investigated. Results showed the LIPUS enhancement effects are dose dependent, LIPUS exposure should be longer than 10 minutes/day in order to elicit a significant effect. Calcium deposition was higher when LIPUS exposure was done twice per day instead of one. Although individual variation exists, optimal LIPUS intensity range was between 60-120 mW/cm2 ISATA (Spatial Average Temporal Average Intensity). The interaction mechanism between LIPUS and cells was also investigated. Microbubbles were added to the culture during LIPUS exposure to find out whether cavitation is involved in the interaction. Flow sensor primary cilium was also studied in order to verify that ultrasound is transduced through fluid flow. Results showed cavitation may not be a contributing factor to osteogenesis, and primary may be involved in the transduction of LIPUS stimulation. This study demonstrated that osteogenesis of hMSCs encapsulated in collagen constructs could be enhanced by LIPUS. The LIPUS parameters were also optimized. The LIPUS interaction pathways were also being better understood. This thesis study will be a paradigm for cellular mechanotransduction studies and put an important step forward for therapeutic ultrasound. / published_or_final_version / Electrical and Electronic Engineering / Master / Master of Philosophy

Thesis (M.App.Sc.) - Carleton University, 2007. / Includes bibliographical references (p. 148-150). Also available in electronic format on the Internet.