Towards the development of an all-optical, non-contact, photon absorption remote sensing (PARS) endomicroscope for blood vasculature imaging

Abstract

The need for high-resolution, label-free imaging techniques has spurred the development of advanced endoscopic technologies for real-time tissue characterization. This thesis presents the design, development, and validation of the first forward-viewing, non-contact, all-optical Photon Absorption Remote Sensing (PARS) endomicroscope for in vivo vascular imaging. The proposed system is designed to leverage the endogenous optical absorption of hemoglobin to achieve high-resolution contrast, without the use of exogenous labels or acoustic coupling, addressing longstanding limitations of conventional absorption-based and scattering-based imaging modalities.Two prototype designs were developed using image guide fiber (IGF) technology and achromatic graded-index (GRIN) lenses, with systematic de-risking experiments guiding their evolution. The first prototype (P1) achieved a resolution of ~1 µm and signal-to-noise ratio (SNR) of 22 dB, demonstrating the feasibility of high-fidelity PARS imaging within a 1.6mm outer diameter (OD) device footprint. A second design (P2) was introduced to address constraints in working distance and imaging depth for in vivo use, trading resolution for improved accessibility in biological tissues. This work establishes a novel platform for PARS miniaturization and integration with widefield endoscopy, positioning the technology for future applications, including real-time, in situ virtual biopsies, blood oxygenation measurement, and surgical guidance within internal bodily cavities. The results represent a foundational advancement in the translation of PARS microscopy to clinical settings and lay the groundwork for real-time, high-resolution endoscopic diagnostics.