| dc.description.abstract | The risk and burden of treating skin and soft tissue infections using antibiotic therapies is increasing due to the rising incidence of methicillin-resistant Staphylococcus aureus and other Gram-positive, multidrug-resistant bacteria. Antimicrobial photodynamic therapy (aPDT) has shown promise in treating skin infections without inducing new resistances. In this regard, it has recently been discovered that Gram-positive bacteria utilize a noncanonical method of synthesizing heme that results in the accumulation of coproporphyrin III (CPIII) instead of the usual protoporphyrin IX (PPIX). While CPIII and PPIX are both porphyrin molecules, and thus share many similar characteristics, the efficacy of properly utilizing CPIII as a photosensitizer is poorly understood. Thus, the first goal of this work was to gauge the maximum efficacy that can be achieved using CPIII-mediated aPDT. The optical parameters of the treatment were optimized and the resulting dose-responses for the aPDT of S. aureus were characterized. The results were then used to predict the treatment efficacy at different depths in the skin.
One of the major limiting factors in developing effective clinical PDT treatments is the lack of accurate and predictive dosimetry. Current measurement techniques do not provide accurate, real-time, and spatially-resolved monitoring of photosensitizer or oxygen concentrations in the target tissue without halting the treatment. To address this, the second goal of this work was to develop a combined treatment and dosimetry system that employs fluorescence imaging and spatial frequency domain imaging (SFDI), a modality that leverages patterned illumination to produce optical property maps, to monitor implicit and explicit dosimetry parameters. To enable the validation of the system, a new method of producing broadband, tissue optical phantoms was first developed. Phantoms made using this method were then used to determine the impact of sub-diffuse scattering on the accuracy of SFDI at different combinations of polarization and scattering phase function. Finally, the overall performance of the combined system was assessed, including its ability to produce quantitative fluorescence images. This system, along with the characterization of CPIII-aPDT, will allow for the development of effective alternatives to treating skin infections without antibiotics, helping to prevent further development of antibiotic-resistant bacteria. | |
