The increased incidence of antibiotic-resistant gram-positive bacteria, like methicillin-resistant S. aureus (MRSA), necessitates treatments that eliminate the potential of developing further resistance. Antimicrobial photodynamic therapy (aPDT) has shown promise as gram-positive infections can be specifically photosensitized by inducing the accumulation of coproporphyrin III (CPIII) through the administration of VU0038882 (‘882), a small-molecule activator of coproporphyrinogen oxidase, and delta-aminolevulinic acid hydrochloride (ALA). While the phototoxic effects of CPIII are most pronounced when stimulated with 395nm light, corresponding to its Soret absorption-band, the high absorption of the skin at that wavelength reduces the efficacy in vivo by three orders of magnitude as compared to in vitro. Although the issue of light penetrance can be mitigated by using red-shifted wavelengths targeting the Q-bands of CPIII (λpeak=498/530/565/619nm), the efficiency of cytotoxic reactive oxygen species (ROS) production and bacterial killing drastically reduces. Though this inefficiency can be partially overcome through an increased light dose, photoinactivation of CPIII and oxygen depletion limits this process to a maximum effective light dose. To overcome these limitations and improve the overall efficacy of CPIII-targeted aPDT, we designed and built a novel multi-LED light source and explored the effect of simultaneously targeting the Soret-band and Q-bands. We present that lower radiant exposures of blue light in conjunction with a higher exposure of green or red light increases the amount of bacterial killing by 1 to 3 logs in vitro as compared to either treatment alone. This enhancement is expected to increase when utilized in vivo due to differences in penetrance.
This work focuses on pulsed terahertz imaging for the application of surgical margin assessment of breast cancer. Various phantom tissue types and orientations are tested here to refine imaging methodology that can detect breast cancer up to 0.5-1.0 mm from the edge of the sample. The depth of the cancer within the sample is estimated using time of flight analysis of the reflected peaks in the pulsed time domain signal. Breast tissue phantoms have been designed to resemble fresh infiltrating ductal carcinoma, fibroglandular tissue, and fatty tissue of the breast to accomplish this work.
The goal of this work was to develop phantoms that match the refractive indices and absorption coefficients between 0.15 and 2.0 THz of the freshly excised tissues commonly found in breast tumors. Since a breast cancer tumor can contain fibrous and fatty tissues alongside the cancerous tissues, a phantom had to be developed for each. In order to match the desired properties of the tissues, oil in water emulsions were solidified using the proven phantom component TX151. The properties of each potential phantom were verified through THz time-domain spectroscopy on a TPS Spectra 3000. Using this method, phantoms for fibrous and cancerous tissue were successfully developed while a commercially available material was found which matched the optical properties of fatty tissue.