Mammographic techniques used for screening programmes need to be of the highest quality; hence, the need of a good phantom to mimic breast response to radiation. The phantom materials must be sensitive to small changes in the mammography system and provide a means of evaluating the absorbed dose to the breast. These materials have to provide the same attenuation properties as the real tissues being simulated, for the radiation modalities being investigated. Cross-linked hydrophilic copolymers have the potential to be good phantom materials for the breast as their elemental compositions are similar to soft tissue. Two types of hydrophilic copolymer materials used in this study were designated as ED1S and ED4C. They were made from a certain proportionate mixture of methyl methacrylate and vinyl pyrrolidone. The physical properties of the materials such as liquid uptake and dimensional changes in hydration and dehydration processes were studied. The equilibrium water content of ED1S and ED4C fully hydrated in water was 55% and 70% respectively. The samples underwent distortion when dehydrated and a volume approximation formula for the dehydrated samples was derived. The linear attenuation coefficient and the mass attenuation coefficient of the hydrophilic copolymer materials at photon energies in the mammographic energy region were determined. Both a single beam transmission method and a photon transmission tomography method were used. The results were compared with XCOM calculated attenuation coefficients of water and average breasts using the elemental composition found in the literature. It was found that the mass attenuation coefficient of dry hydrophilic copolymer samples closely fit the XCOM calculated old-age breast (Breast 3) and samples fully hydrated in water fit the calculated young-age breast (Breast 1). Measurements were also carried out to determine the linear attenuation coefficient of normal and abnormal breast tissues at four photon energies in the mammographic energy region. The values found were in good accord with calculated average breast values. However, more studies need to be done as only three samples were used. The electron density of the hydrophilic copolymer materials was determined by using the Compton scattering technique. The electron density for dry ED1S sample was (3.1 +/- 0.4) x 1023 electrons per cm3 and for dry ED4C was (4.4 +/- 0.4) x 1023 electrons per cm3.

Blood perfusion is the local, non-directional blood flow through tissue. It is measured as the volumetric flow rate of blood through a given volume of tissue. One method that has been developed for measuring blood perfusion is a probe that measures the temperature response of the tissue when a thermal event is applied. From the temperature response, the blood perfusion and contact resistance can be estimated by comparing the experimental response to a predicted response, and employing Gaussian minimization techniques to estimate the blood perfusion and contact resistance. The objective of this research was to assess the measurement repeatability and sensitivity of the blood perfusion probe by testing the probe on phantom tissue, such that the effects of physiologic or pathologic conditions on the blood perfusion could be eliminated. Another objective was to conduct a preliminary in vivo study using rats for the purpose of establishing proper experimental protocols for future testing of the blood perfusion probe. A phantom tissue test stand comprised of porous material and water to simulate tissue and blood, respectively, was constructed for the phantom study. Inlet flow rates into the porous media ranging between 0 cc/min and 30 cc/min were tested. To test the measurement repeatability 7 flow rates (0, 5, 10, 15, 20, 25 and 30 cc/min) were tested on two different days. To test the measurement sensitivity of the probe, flow rates between 0 and 10 cc/min, and 15 and 20 cc/min were tested at intervals of 1 cc/min. From the phantom study it was concluded that the probe displayed good measurement repeatability, as the trend in perfusion as a function of inlet flow rates for both days was found to be the same. It was also found that the data collected using the probe yielded significantly different perfusion estimates for different flow rates, as statistical analyses show that the average perfusion differences between flow rates are truly independent within a 90% confidence interval, for flow differences above 4 cc/min. It was found that for flow rates below 4 cc/min the probe sensitivity was significantly reduced. For the in vivo study it was concluded that the probe can be used to obtain estimates of perfusion from rats. This preliminary study also served to establish proper experimental protocols for future tests. / Master of Science

The Thermoelectric Perfusion Probe is a completely electronic system that cyclically heats and cools tissue to measure blood perfusion. The probe produces the thermal event with a thermoelectric cooler and then measures the resulting heat flux and temperatures: the arterial temperature and the sensor temperature (the temperature between the heat flux gage and the skin). The Thermoelectric Perfusion Probe was validated and calibrated on a phantom tissue test stand, a system that simulates perfusion with known, controlled flow. With the new pressed sensor technology, a thermocouple sealed to a heat flux gage, the sensor temperature and the heat flux are simultaneously recorded. The pressed sensor tests validated the program used to predict perfusion for the Thermoelectric Perfusion Probe. This perfusion estimation program can determine the tissues perfusion regardless of how the thermal event is created (i.e. convective cooling, convective heating, conductive heating). Based on experimentation, the Thermoelectric Perfusion Probe displays good repeatability and sensitivity for continuously measuring perfusion. The sensitivity and repeatability of the Thermoelectric Perfusion Probe was proven when the perfusion estimates were compared to the perfusion estimates predicted by the Convective Perfusion Probe, a previously validated perfusion probe, and the CFD Flow Model, a computational model of the phantom tissue test stand. / Master of Science

Mesoporous silica particles are of significant interest for biomedical applications due to their good general biocompatibility compared to other nanoparticle matrices such as quantum dots, high specific surface areas up to 1000 m2/g, and extreme synthetic tunability in terms of particle size, pore size and topology, core material, and surface functionalization. For one application, drug delivery, mesoporous silica nanoparticles (MSNs) of two pore structures, MCM-41 – parallel, hexagonally ordered pores approximately 3 nm in diameter – and wormhole (WO) – interconnected, disordered pores also approximately 3 nm in diameter – were synthesized with particle diameters under 100 nm. Additionally, a magnetic Fe3O4 nanoparticle core was incorporated into Fe3O4-core WO-MS-shell particles. The particles were loaded with doxorubicin, a chemotherapeutic, and the drug release into phosphate buffered saline (PBS, 10 mM, pH 7.4) at 37 °C was monitored by fluorescence spectroscopy. The data were fit to three models: Korsmeyer-Peppas, first order exponential release, and Weibull. The Korsmeyer-Peppas model provided useful information concerning the kinetics and mechanism of drug release from each MSN type. A small but statistically significant difference in the release kinetics was found due to the different pore topologies. A much larger kinetic effect was observed due to the inclusion of an iron oxide core. Applying a static magnetic field to the Fe3O4-core WO-MS shell particles did not have a significant impact on the doxorubicin release. This is the first time that the effects of pore topology and iron oxide core have been isolated from pore diameter and particle size for these materials. In vitro cell studies were conducted to determine the cytotoxicity of the bare and doxorubicin-loaded materials against three cancerous cell lines – A549 human lung carcinoma cells, HEC50CO human endometrial cancer cells, and CT26 mouse colon cancer cells. The MCM-41 and WO MSNs generally displayed similar toxicities within each cell line, and the Fe3O4-core WO-MS shell particles were less toxic. Doxorubicin-loaded particles generally displayed greater toxicity than bare MSNs, but the A549 cells were very resistant to all concentrations of MSNs tested. For another biomedical application, tissue phantom development, mesoporous silica particles with approximately 10 μm diameters and C18 surface functionalization were evaluated for their use as a substrate for optical tissue phantoms. Tissue phantoms are synthetic imitations of biological material, and C18-modified silica provides a substrate that is simple to load with optically active biological molecules. The molecules are then hydrophobically trapped to maintain a clear optical boundary between the biological loading within the particle and an aqueous suspension gel. Several preparation techniques were evaluated for the dispersal of hydrophobic particles in aqueous media, and qualitative analysis indicated that surfactant coating of the outer surface could fully disperse the hydrophobic particle while maintaining the clear optical boundary. A novel analysis was developed to provide a single numerical indicator of clustering for a quantitative assessment of particle dispersal in tissue phantoms.

Health-care associated infections (HAIs) on medical implant surfaces present a unique challenge to physicians due to their existence in the biofilm phenotype which defends the pathogen from antibiotics and the host’s own immune system. A 2004 study in the U.S. showed that 2 to 4% of implanted devices become infected and must be treated via surgical explantation—a process that is both expensive and dangerous for the patient. A potential, alternative strategy to antibiotics and surgery is to use heat delivered wirelessly by a magnetic coating. This thermal treatment strategy has the potential to kill these HAIs directly on the implanted surface and without the patient requiring surgery. This thesis introduces an iron oxide nanoparticle composite coating that is wirelessly heated using energy converted from an alternating magnetic field. Iron oxide nanoparticle composites are demonstrated to be remotely heated in both hydrophilic and hydrophobic polymer composites. In designing the composite coating, multiple parameters were investigated for how they impact the normalized heating rate of the material. Specifically, the amount of iron in the coating, the coating thickness, the polymer type, and the orientation of the coating relative to the applied magnetic field were investigated. Power output was shown to increase proportionally with iron loading whereas nearly two times the amount of power output was observed for the same coatings positioned parallel to magnetic field lines versus those positioned perpendicular—a result believed to be due to magnetic shielding from neighboring particles. Microscope slides coated with 226 µm of composite delivered up to 10.9 W cm⁻² of power when loaded with 30.0% Fe and positioned parallel in a 2.3 kA m⁻¹AMF. Pseudomonas aeruginosa biofilms were grown directly on these coatings and heated for times ranging from 1 to 30 min and temperatures from 50 to 80 °C. Less than one order of magnitude of cell death was observed for temperatures less than 60 °C and heat shock times less than 5 min. Up to six orders of magnitude reduction in viable bacteria were observed for the most extreme heat shock (80 °C for 30 min). Introducing this wirelessly heated composite into the body has the potential to kill harmful bacteria but at the risk of thermally damaging the surrounding tissue and organs if the treatment is not designed and predicted intelligently. Thermal energy will propagate differently depending on the surrounding heat sink, with convective heat sinks (i.e. those due to blood flow) requiring much more power to reach the same surface temperature than a conduction-only heat sink. To study how heat is transferred in biological tissues, a robust, poly(vinyl alcohol) tissue phantom was developed that can be poured to accommodate any geometry, is volume stable in water and under thermal stress, and can be modified with inert particle fillers to adjust its thermal conductivity from 0.475 to 0.795 W m⁻¹°C⁻¹. In vitro heat transfer was measured through this hydrogel tissue phantom with at least 10 °C of temperature rise, penetrating 5 mm of tissue in less than 120 sec for an 80 °C boundary condition. A computational model was used to solve three-dimensional energy transfer through a combined fluid mimic/tissue mimic heat sink spanning the same surface boundary condition. The model was validated with experimental models using a custom designed heat transfer station. This scenario is applicable in the instance where the same coating is subject to starkly different heat sinks: half subject to convective heat loss, half to conductive heat loss. Based on these conditions, a magnetic coating would need to be designed that has a power gradient up to 15 times larger on the fluid half versus the other.

Laser therapies can provide a minimally invasive treatment alternative to surgical resection of tumors. However, therapy effectiveness is limited due to nonspecific heating of target tissue, leading to healthy tissue injury and extended treatment durations. These therapies can be further compromised due to heat shock protein (HSP) induction in tumor regions where non-lethal temperature elevation occurs, thereby imparting enhanced tumor cell viability and resistance to subsequent therapy treatments. Introducing nanoparticles (NPs), such as multi-walled nanotubes (MWNTs) or carbon nanohorns (CNHs), into target tissue prior to laser irradiation increases heating selectivity permitting more precise thermal energy delivery to the tumor region and enhances thermal deposition thereby increasing tumor injury and reducing HSP expression induction. This research investigates the impact of MWNTs and CNHs in untreated and laser-irradiated monolayer cell culture, tissue phantoms, and/or tumor tissue from both thermal and biological standpoints. Cell viability remained high for all unheated NP-containing samples, demonstrating the non-toxic nature of both the nanoparticle and the alginate phantom. Up-regulation of HSP27, 70 and 90 was witnessed in samples that achieved sub-lethal temperature elevations. Tuning of laser parameters permitted dramatic temperature elevations, decreased cell viability, and limited HSP induction in NP-containing samples compared to those lacking NPs. Preliminary work showed MWNT internalization by cells, which presents imaging and multi-modal therapy options for NT use. The lethal combination of NPs and laser light and NP internalization reveals these particles as being viable options for enhancing the thermal deposition and specificity of hyperthermia treatments to eliminate cancer. / Master of Science

Presented is a radiometric sensor and associated electromagnetic propagation models, developed to facilitate non-invasive core body temperature extraction. The system has been designed as a close-proximity sensor to detect thermal emissions radiated from deep-seated tissue 1 cm – 3 cm inside the human body. The sensor is intended for close proximity health monitoring applications, with potential implications for deployment into the improved astronaut liquid cooling garment (LCG). The sensor is developed for high accuracy and resolution. Therefore, certain design issues that distort the close proximity measurement have been identified and resolved. An integrated cavity-backed slot antenna (CBSA) is designed to account for antenna performance degradation, which occurs in the near field of the human body. A mathematical Non-Contact Model (NCM) is subsequently used to correlate the observed brightness temperature to the subsurface temperature, while accounting for artifacts induced by the sensor’s remote positioning from the specimen. In addition a tissue propagation model (TPM) is derived to model incoherent propagation of thermal emissions through the human body, and accounts for dielectric mismatch and losses throughout the intervening tissue layers. The measurement test bed is comprised of layered phantoms configured to mimic the electromagnetic characteristics of a human stomach volume; hence defines the human core model (HCM). A drop in core body temperature is simulated via the HCM, as the sensor monitors the brightness temperature at an offset distance of approximately 7 mm. The data is processes through the NCM and TPM; yielding percent error values < 3%. This study demonstrates that radiometric sensors are indeed capable of subsurface tissue monitoring from the near field of the body. However, the following components are vital to achieving an accurate measurement, and are addressed in this work: 1) the antenna must be designed for optimum functionality in close proximity to biological media; 2) a multilayer phantom model is needed to accurately emulate the point of clinical diagnosis across the tissue depth; 3) certain parameters of the non-contact measurement must be known to a high degree of accuracy; and 4) a tissue propagation model is necessary to account for electromagnetic propagation effects through the stratified tissue.