Thesis (Ph.D.)--University of California, San Francisco with the University of California, Berkeley, 2008. / Source: Dissertation Abstracts International, Volume: 69-06, Section: B, page: 3693. Adviser: Daniel Fletcher.

Thesis (Ph.D.)--University of California, San Francisco, 2006. / Source: Dissertation Abstracts International, Volume: 67-05, Section: B, page: 2685. Adviser: Daniel B. Vigneron.

Thesis (Ph.D.)--University of California, San Francisco, 2006. / Source: Dissertation Abstracts International, Volume: 67-05, Section: B, page: 2455. Adviser: Daniel Fried.

Thesis (Ph.D.)--University of California, San Francisco with the University of California, Berkeley, 2006. / Source: Dissertation Abstracts International, Volume: 67-08, Section: B, page: 4549. Adviser: Sarah J. Nelson.

Thesis (Ph. D.)--University of California, San Francisco with the University of California, Berkeley, 2009. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3649. Adviser: Francis C. Szoka.

<p> Accurate, cross-scanner assessment of in-vivo air density used to quantitatively assess amount and distribution of emphysema in COPD subjects has remained elusive. Hounsfield units (HU) within tracheal air can be considerably more positive than -1000 HU. With the advent of new dual-source scanners which employ dedicated scatter correction techniques, it is of interest to evaluate how the quantitative measures of lung density compare between dual-source and single-source scan modes. This study has sought to characterize in-vivo and phantom-based air metrics using dual-energy computed tomography technology where the nature of the technology has required adjustments to scatter correction. </p><p> Anesthetized ovine (N=6), swine (N=13: more human-like rib cage shape), lung phantom and a thoracic phantom were studied using a dual-source MDCT scanner (Siemens Definition Flash. Multiple dual-source dual-energy (DSDE) and single-source (SS) scans taken at different energy levels and scan settings were acquired for direct quantitative comparison. Density histograms were evaluated for the lung, tracheal, water and blood segments. Image data were obtained at 80, 100, 120, and 140 kVp in the SS mode (B35f kernel) and at 80, 100, 140, and 140-Sn (tin filtered) kVp in the DSDE mode (B35f and D30f kernels), in addition to variations in dose, rotation time, and pitch. To minimize the effect of cross-scatter, the phantom scans in the DSDE mode was obtained by reducing the tube current of one of the tubes to its minimum (near zero) value.</p><p> When using image data obtained in the DSDE mode, the median HU values in the tracheal regions of all animals and the phantom were consistently closer to -1000 HU regardless of reconstruction kernel (chapters 3 and 4). Similarly, HU values of water and blood were consistently closer to their nominal values of 0 HU and 55 HU respectively. When using image data obtained in the SS mode the air CT numbers demonstrated a consistent positive shift of up to 35 HU with respect to the nominal -1000 HU value. In vivo data demonstrated considerable variability in tracheal, influenced by local anatomy with SS mode scanning while tracheal air was more consistent with DSDE imaging. Scatter effects in the lung parenchyma differed from adjacent tracheal measures.</p><p> In summary, data suggest that enhanced scatter correction serves to provide more accurate CT lung density measures sought to quantitatively assess the presence and distribution of emphysema in COPD subjects. Data further suggest that CT images, acquired without adequate scatter correction, cannot be corrected by linear algorithms given the variability in tracheal air HU values and the independent scatter effects on lung parenchyma.</p>

<p> The primary goal of my thesis was to address my hypothesis that: there is preferential perfusion of the hindbrain regions, controlling autonomic function. To test this hypothesis I developed a system for delivering hypoxic challenges to volunteers while they were in the MRI. I developed NIRS protocols that allowed monitoring of the cerebellum. And I developed MRI methods that allowed for PC MRI to be used to monitor flow to the forebrain and hindbrain. Finally I combined these elements to investigate how the brain would react to hypoxia. Ultimately neither NIRS nor MRI detected systematic differences between the forebrain and hindbrain response to hypoxia but the developed methods are available for future studies that aim to explore the hemodynamic response in the developing brain or in adults with pathological conditions. </p>

<p> <b>Background:</b> The applications for rapid prototyping have expanded dramatically over the last 20 years. In recent years, additive manufacturing has been intensely investigated for surgical implants, tissue scaffolds, and organs. There is, however, scant literature to date that has investigated the viability of 3D printing of surgical instruments. </p><p> <b>Materials and Methods:</b> Using a fused deposition manufacturing (FDM) printer, an army/ navy surgical retractor was replicated from polylactic acid (PLA) filament. The retractor was sterilized using standard FDA approved glutaraldehyde protocols, tested for bacteria by PCR, and stressed until fracture in order to determine if the printed instrument could tolerate force beyond the demands of an operating room. </p><p> <b>Results:</b> Printing required roughly 90 minutes. The instrument tolerated 13.6 kg of tangential force before failure, both before and after exposure to the sterilant. Freshly extruded PLA from the printer was sterile and produced no PCR product. Each instrument weighed 16g and required only $0.46 of PLA. </p><p> <b>Conclusions:</b> Our estimates place the cost per unit of a 3D printed retractor to be roughly 1/10th the cost of a stainless steel instrument. The PLA Army/ Navy is strong enough for the demands of the operating room. Freshly extruded PLA in a clean environment, such as an OR, would produce a sterile, ready to use instrument. Due to the unprecedented accessibility of 3D printing technology world wide, and the cost efficiency of these instruments, there are far reaching implications for surgery in some underserved and less developed parts of the world.</p>

<p> Personalized medicine requires the development of new technologies for controlled or targeted drug delivery. Three-dimensional (3D) printing and additive manufacturing techniques can be used to generate customized constructs for bioactive compound delivery. Nanotechnology in the form of nanoparticles, used as a stand-alone construct or for material enhancements, can significantly improve established biomaterials such as PMMA based bone cements or enable new technology to have enhanced capabilities. Combinations of the technologies can be used in such applications as infectious disease treatments, chemotherapeutic targeted drug delivery or targeted delivery of nearly any bioactive compound. </p><p> Chemotherapeutic or antibiotic enhanced 3D printing filaments were invented and designed to allow for the fabrication of antibiotic beads, drug eluting catheters, drains, stents, screws or any bioactive construct. Halloysite nanotubes (HNTs) were investigated as a modular platform and solely or in combinations were coated in metals including: iron for magnetic targeted delivery including hyperthermia, gold for laser targeted hyperthermia or barium as a contrast agent for visualization. The particles were test loaded with antibiotics or chemotherapeutics as well as coated in biocompatible coatings containing lipids or layered polyelectrolytes. Nanoparticles were added to 3D printing filaments or bone cements to test increases in strength, contrast or pore size.</p><p> 3D print filaments and bioactive constructs that eluted gentamicin sulfate were tested using clinical microbiology lab standards and were shown to inhibit bacterial growth. 3D print filaments that eluted methotrexate were shown to inhibit proliferation of osteosarcoma cells and also provided a means for sustained drug release. Halloysite was successfully shown as a modular platform that could be highly customized for patient specific uses. Single coatings or combinations of magnetically susceptible iron coatings, gold coatings, drug loading of multiple bioactive compounds and biocompatible coatings were also developed. Bone cements with barium-coated particles were shown to have enhanced contrast.</p><p> The first ever ability to create and use bioactive 3D printing filaments on consumer printers was realized and HNTs were developed as proof of principle for multifunctional and real time customizable nanoparticle platforms. Nanoparticles as additives showed ways to modify established biomaterials or 3D printing filaments with enhanced features and properties.</p>

<p> The goal of this research is to study tissue growth via developing mathematical formulations and computational modeling. Tissue growth modeling has many applications --- including tumor growth, wound healing, bone remodeling, epithelial tissue remodeling, and other problems in developmental biology. Key to this study is incorporating the results of the analysis of non-destructive medical images that augment the models. Quantitative image analysis for the purpose of providing input parameters for and validation of tumor growth models (TGMs) is discussed. Two types of computational TGMs are studied in detail: one is based on the logistic equation, the other is based on the theory of porous media, or mixture theory. For the mixture-based model, we developed an algorithm that couples a level set method to track tumor boundaries while the tissues themselves are treated as a perfused mixture. After the mathematical foundation of each of the TGMs is formulated, we discuss implementation aspects, along with computational results. Finally, we validate the computational results with experimental observations of tumor volume versus time via imaging data acquired from animal models. The RMS deviation between predicted and observed values is as close as 11\% of the time-averaged volume.</p>