Development of multi-modal endoscopic optical biopsy for laryngeal (head and neck) cancer screening

Abstract

The work presented in this thesis aimed to study the application of optical coherence tomography (OCT), fluorescence lifetime imaging microscopy (FLIM), polarization resolved (PR) imaging and hybrid multi / hyper-spectral / structured lighting (MS / SL) to investigate their potential for diagnostic contrast of diseased head and neck mucosal tissues, with a particular emphasis on head and neck (laryngeal) cancer. Initially, an ex vivo study utilising bench-top OCT was undertaken to provide a baseline reference data-set on mucosal sub-sites from a laryngectomy patient. Technical development and pre-clinical (phantom) testing of a novel, endoscopic miniaturized OCT arrangement followed, prior to single-centre, in vivo clinical trial of the prototype arrangement at the NHS site. The portable OCT platform was adapted for dual hand-held and endoscopic application within the ENT outpatient clinic, allowing evaluation and preliminary correlation of OCT images (larynx and skin) with histopathology sections. Design considerations and feedback to the technical team, for further optimization of the OCT platform, concluded this work-stream. FLIM application thereafter, also involved design considerations for portability and endoscopic adaptation, prior to single-site clinical application. Use was limited to ex vivo diseased tissues extracted from the larynx, nasal cavity and oropharynx, exclusively within the busy operating theatre environment. As with OCT, limited histopathology correlation allowed commentary on tissue contrast between laryngeal disease states and between other head and neck sub-site mucosal pathologies. Similarly for PR, MS and SL, portable imaging assemblies were installed and optimised for operating room-based endoscopic application. Both ex vivo and in vivo application across head and neck mucosal sub-sites, and across disease states, was performed and contrast patterns reported. All four optical modalities demonstrated useful and potentially complimentary optical contrast capabilities, providing critical pilot data for future co-assembly of a multi-modal, optical imaging platform for head and neck (cancer and non-cancer, endoscopic and topical) disease screening. In modular format, the same multi-modality optical imaging platform may support augmented vision during microscope and robot-assisted disease resection, optical needle biopsies, in vivo optical observation of disease pathogenesis, as well as allowing objective non-invasive optical characterization of response to pharmaceutical and other treatments.