Thesis (Ph.D)--Biomedical Engineering, Georgia Institute of Technology, 2009. / Committee Chair: Hu, Xiaoping; Committee Member: Brummer, Marijn; Committee Member: Duong, Tim; Committee Member: Keilholz, Shella; Committee Member: Schumacher, Eric. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Photothermal cancer therapy is a potential alternative to surgery and involves selective tissue destruction using thermal energy. Targeted photoabsorbers, used in conjunction with matching a continuous wave laser, make photothermal therapy both noninvasive and tumor-specific. However, to become clinically relevant, there is a need to develop an imaging technique to identify tissue composition and to detect the presence of photoabsorbers in the tumor volume before therapy; to monitor the temperature rise during therapy; and to assess the tumor damage after therapy. In this study, a combined ultrasound and photoacoustic imaging system was designed to assist photothermal therapy. The imaging system was tested on tissue mimicking phantoms, ex-vivo porcine tissue samples, ex-vivo mice and in-vivo mice. First, ultrasound imaging was utilized to differentiate between water-based and lipidbearing tissue. A combined ultrasound and photoacoustic imaging system was then assembled to identify the presence and spatial location of gold nanoparticles. Multiwavelength photoacoustic imaging was used to further confirm the presence of nanoparticles. Temperature monitoring algorithms, using both temperature-dependent time shifts in ultrasound signals and amplitude changes in photoacoustic signals, were developed. Finally, photothermal therapy was carried out on tumor-bearing nude mice using in-vivo ultrasound and photoacoustic imaging to identify the tumor boundary, detect the nanoparticles and monitor the temperature elevation. The results of the studies show that ultrasound and photoacoustic imaging provide complementary and clinically relevant information. Overall, there is potential of using the ultrasound and photoacoustic imaging system to plan, guide and monitor photothermal therapy. / text

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Early diagnosis of disease and developing targeted therapeutics are two major goals of medical research to which nanotechnology can contribute a variety of novel approaches and solutions. This work utilized an optical phenomenon specific to metallic nanoparticles, surface-enhanced Raman spectroscopy (SERS), as a nanomedicine research tool to aid in the progression toward these goals. Single-particle SERS studies were streamlined to identify particles or aggregates with potentially high enhancement factors (EFs) for applications requiring ultrasensitive and possibly single-molecule detection. SERS was used to probe the changes in surface chemistry of nanoparticles for optimizing nanomedicine applications. Fundamental SERS imaging parameters were identified, and a new algorithm for multiplexed SERS imaging was developed and tested. Novel particle-based contrast agents were also developed. Polystyrene hollow beads with a single hole on the surface were fabricated and used to encapsulate contrast agents for a variety of medical imaging modalities. Saline was encapsulated as a novel contrast agent for thermoacoustic tomography (TAT). Encapsulation of X-ray computed tomography (CT) and magnetic resonance (MR) imaging was also performed and tested.

Mitral valve (MV) disease is responsible for approximately 2,581 deaths and 41,000 hospital discharges each year in the US. Mitral regurgitation (MR), retrograde blood from through the MV, is often an indicator of MV disease. Surgical repair of MVs is preferred over replacement, as it is correlated with better patient quality of life. However, replacement rates are still near 40% because MV surgical repair expertise is not spread across all hospitals. In addition, 15-80% of surgical repair patients have recurrent MR within 10 years. Quantitative patient-specific models could aid these issues by providing less experienced surgeons with additional information before surgery and a quantitative map of patient valve changes after surgery. Real-time 3D echocardiography (RT3DE) can provide high quality 3D images of MVs and has been used to generate quantitative models previously. However, there is not currently an efficient, dynamic, and validated method that is fast enough to use in common practice. To fill this need, a tool to generate quantitative 3D models of mitral valve leaflets from RT3DE in an efficient manner was created. Then an in vitro echocardiography correction scheme was devised and a dynamic, in vitro validation of the tool was performed. The tool demonstrated that it could generate dynamic, complex MV geometry accurately and more efficiently than current methods available. In addition, the ability for mesh interpolation techniques to reduce segmentation time was demonstrated. The tool generated by this study provides a method to quickly and accurately generate MV geometry that could be applied to dynamic patient specific geometry to aid surgical decisions and track patient geometry changes after surgery.

This thesis is concerned with exploiting the native optical coherence tomography (OCT) contrast mechanism in new ways and with a new contrast mechanism, in both cases to enhance the information content of the tomographic image. Through experiments in microsphere solutions, we show that static speckle contains information about local particle density when the effective number of scatterers in the OCT resolution volume is less than about five. This potentially provides contrast enhancement in OCT images based on local scatterer density, and we discuss the experimental conditions suited to utilising this in biological tissue. We also describe the corrupting effects of multiple scattering, a ubiquitous phenomenon in OCT, on the information content of the static speckle. Consequently, we detail the development of polarisation-based metrics for characterising multiple scattering in OCT images of solid biological tissues. We exploit a detection scheme used for polarisation-sensitive contrast for a new purpose. We present experiments demonstrating the behaviour of these metrics in liquid phantoms, and in biological tissues, ranging from homogeneous non-birefringent to highly heterogeneous and birefringent samples. We discuss the conditions under which these metrics could be used to characterise the relative contribution of single and multiple scattering and, thus, aid in the study of penetration depth limits in OCT. We present a study of a new contrast mechanism - dynamic elastography which seeks to determine the dynamic mechanical properties of tissues. We present a framework for describing the OCT signal in samples undergoing vibrations, and perform experiments at vibration frequencies in the order of tens to hundreds of Hertz, to confirm the theory, and demonstrate the modes of measurement possible with this technique. These modes of measurement, including acoustic amplitude-sweep and frequency-sweep, could provide new information about the local mechanical properties of a sample. We describe a technological advancement enabling, in principle, measurements of local tissue refractive index contrast much deeper within a sample, than is possible with conventional OCT imaging. The design is based on measurement of the optical path length through tissue filling a fixed-width channel situated at the tip of a needle. The needle design and calibration is presented, as well as measurements of scattering phantoms and various biological tissues. This design potentially enables the use of refractive index-based contrast enhancement in the guidance of breast biopsy procedures.

Thesis (Ph.D.)--University of Wollongong, 2006. / Typescript. Includes bibliographical references: leaf 225-237.

Thesis (Ph. D.)--Civil and Environmental Engineering, Georgia Institute of Technology, 2008. / Committee Chair: Germanovich, Leonid; Committee Co-Chair: Skrinjar, Oskar; Committee Member: Mayne, Paul; Committee Member: Puzrin, Alexander; Committee Member: Rix, Glenn.

Thesis (Ph. D.)--University of Sydney, 2007. / Cotutelle thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Discipline of Pharmacology, Faculty of Medicine, University of Sydney and to the Doctoral School: Santé, Sciences et Technologies, University of Tours (France). Title from title screen (viewed Sept. 21, 2007). Includes bibliography. Also issued in print.

Thesis (M.App.Sc.) - Carleton University, 2002. / Includes bibliographical references (p. 94-105). Also available in electronic format on the Internet.