Prolonged periods of non-weightbearing activity result in a significant loss of bone mass which increases the risk of fracture with the initiation of mechanical loading. The loss of bone mass is partially driven by declines in bone formation yet the mechanisms responsible for this decline are unclear. To investigate the limitations of osteoblasts during disuse, marrow ablation was superimposed on hindlimb unloaded mice. Marrow ablation is a useful model to study osteoblast functionality as new cancellous bone is rapidly formed throughout the marrow of a long bone while hindlimb unloading is the most common method used to produce skeletal unloading. The specific hypotheses of this study were aimed at determining if changes in osteoblast functionality, differentiation, and/or proliferation were compromised in non-weightbearing bone in response to a bone formation stimulus. Additionally, the influence of having compromised osteoblast functionality at the time of stimulation was assessed in non-weightbearing bones. Key outcome measures used to address these hypotheses included static and dynamic cancellous bone histomorphometry, bone densitometry, and real-time polymerase chain reaction (PCR) analyses of gene expression. The results document similar ablation-induced increases of cancellous bone in both weightbearing and unloaded animals. Similarly, there was no influence of load on ablation-induced increases in cancellous bone forming surface or mineral apposition rate. Unloading did significantly attenuate the ablation-induced increase in bone formation rate, due to reduced levels of total surface mineralization. When osteoblast functionality was compromised prior to marrow ablation, bone formation rate increases were also attenuated in ablated animals due to reduced mineralization. Additionally, increases in forming surface were attenuated as compared to unloaded animals having normal osteoblast function at the time of ablation. Collectively, these data identify mineralization as the limiting step in new bone formation during periods of disuse. The caveat, however, is that when bone formation is stimulated after a period of unloading sufficient to compromise osteoblast functionality, increases in osteoblast recruitment to the bone surface are compromised.

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Reproduction de : Thèse d'exercice : Médecine. Radiodiagnostic et imagerie médicale : Nantes : 2008. / Bibliogr.

Thesis (Ph. D.)--University of Texas at Austin, 2001. / Vita. Includes bibliographical references. Available also from UMI Company.

Thesis (Ph. D.)--University of Texas at Austin, 2001. / Vita. Includes bibliographical references (leaves 178-183). Available also in a digital version from Dissertation Abstracts.

Femtosecond laser microsurgery has emerged as a remarkable technique for precise ablation of biological systems with minimal damage to their surrounding tissues. The combination of this technique with nonlinear optical imaging provides a means of microscopic visualization to guide such surgery in situ. A clinical endoscope capable of image-guided femtosecond laser microsurgery will provide physicians a means for cellular-level microsurgery with the highest precision. This dissertation focuses the development of a miniaturized fiber-coupled probe for image-guided microsurgery, towards future realization as a clinical endoscope. The first part of the dissertation describes the development of an 18-mm diameter probe. This development includes delivery of femtosecond laser pulses with pulse energy in excess of 1 µJ through air-core photonic bandgap fiber, laser beam scanning by a microelectromechanical system scanning mirror, and development of a new image reconstruction methodology for extracting increased temporal information during Lissajous beam scanning. During testing, the 18-mm probe compares favorably with the state-of-the-art as a microscopic imaging tool and we present the first known demonstration of cellular femtosecond laser microsurgery through an optical fiber. The second part of the dissertation explores further refinement of the design into a streamlined package with 9.6 mm diameter and improved imaging resolution. Study of the optical performance through analytical and computer-aided optical design indicates that simple custom lenses can be designed that require only commercial-grade manufacturing tolerances while still producing a fully aberration-corrected microsurgical endoscope. With the 9.6-mm probe, we demonstrate nonlinear optical imaging, including tissue imaging of intrinsic signals from collagen, using average laser powers 2-3× lower than the current state-of-the-art. We also demonstrate the use of the 9.6-mm probe in conjunction with gold nanoparticles for enhanced imaging and microsurgery through plasmonics. Finally, in the third part of this dissertation, we detail bench-top development of a new clinical application for combined femtosecond laser microsurgery and nonlinear optical imaging: the treatment of scarred vocal folds. We show the utility of femtosecond laser microsurgery for creating sub-epithelial voids in vocal fold tissue that can be useful for enhancing localization of injectable biomaterial treatments. We demonstrate that a single compact fiber laser system can be utilized for both microsurgery and imaging. Furthermore, the proposed clinical technique is shown to be achievable with parameters (e.g., pulse energy, focused spot size) that were found to be attainable with fiber-coupled probes while still achieving ablation speeds practical for clinical use. / text

Electrical and Computer Engineering / A high performance, wireless bio-impedance measurement system has been designed for the purpose of monitoring essential electrical properties of the heart during cardiac ablation. The system is broken into three parts: a spring-loaded device to house a tetrapolar surface probe and sensors, a wireless bio-impedance measurement system, and a desktop base station for graphical data display and acquisition. The system is specifically designed for a tetrapolar-electrode configuration where the two outer electrodes served as a current source operating at 20 kHz with an amplitude of 100 µArms and the two inner electrodes served as voltage sensing electrodes. In addition, the system also has a dedicated channel for current sense. The system is designed to be modular and reconfigurable for different measurement needs. Epochs of both discrete voltage and current samples generated by the voltage-controlled current source are processed using a digital signal processing algorithms to generate admittance measurements. In addition to the admittance’s magnitude and phase, pressure, electrocardiogram (EKG), and temperature (two channels) data are also acquired. The measurements are then wirelessly transmitted from the bio-impedance measurement system to a base station where data are processed and viewed graphically. The final system updates the admittance, pressure, EKG, and two temperature channels at 320 Hz, consumes less than 3 W, and has percent of measurement errors of 7 % and 2 % for capacitive and resistive measurements in the range of 100 pF to 10000 pF and 300 Ω to 1600 Ω, respectively. Instrument design, calibration, verification, and modeling are at the heart of this thesis. In the future, the instrument will be deployed for various bio-impedance measurements that require a high degree of linearity, precision, and a wide input range. / text

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