Towards an Optical Biopsy Tool Using Photon Absorption Remote Sensing

Abstract

Streamlining diagnosis is more important than ever, as the long wait times, resource constraints, and diagnostic inaccuracies place burdens on the healthcare system that climb each year. The development of a tool capable of instantaneous in situ diagnosis would eliminate the excess time and resources used in current diagnostic procedures, and thereby relieve some of these burdens. This could be achieved with an optical biopsy by leveraging light-matter interactions for advanced microscopy in an endoscopic form. However, to date there is no technology able to provide diagnostically equivalent image quality to the gold standard for diagnosis in an endoscopic form. Photon Absorption Remote Sensing (PARS) is a novel imaging modality that utilizes optical absorption contrast to achieve label-free, non-contact microscopy. PARS technology holds promising potential in resolving many of the challenges faced in the development of an optical biopsy tool. This thesis explores the initial development of a PARS endoscope capable of in vivo microvascular imaging through multiple phases of development. The first stage investigated the performance of a dual green PARS bench-top system, utilizing green excitation and detection wavelengths to address chromatic aberrations in the final endoscopic form. The system was confined to a green excitation wavelength in order to target the absorption of hemoglobin for vascular imaging. It was then paired with a green detection wavelength for the first time, unlike typical PARS microscopes that rely on near-infrared (NIR) wavelengths for detection. Both phantom and in vivo samples were imaged to validate the performance of the system, showing functionality and sensitivity comparable to NIR PARS systems. The next phase explored the transition of a stationary PARS bench-top system to a free imaging head using optical fiber. This introduced many challenges, such as high losses and inherent noise, that had to be addressed through careful design, assembly and optimization. Two types of specialized optical fiber were tested by imaging phantom targets and in vivo chicken embryo samples. The double clad fiber setup showed strong performance with excellent contrast, signal to noise ratio and sensitivity in the PARS images. The final stage included miniaturizing the imaging head to achieve an endoscopic form factor. Various miniature objective lens designs were developed, and tested in the system. The successful design was capable of imaging both in phantoms and in vivo, demonstrating, for the first time, vasculature imaged using PARS through optical fiber. This research lays the groundwork in the development of a PARS endoscope capable of providing a gold standard quality, instantaneous diagnosis in situ. It demonstrates a successful design capable of capturing relevant biomarkers in vivo using endoscopic PARS technology. The improved understanding of the design requirements for a more efficient system, and insight into the fundamental limitations, highlight future directions to further improve this device. This puts us one step closer towards achieving a successful optical biopsy tool that could streamline diagnosis, improve the outcome, safety and experience of the patient, and significantly reduce the cost burden on the health system.