title: Fluorescence lifetime imaging with distance and ranging for biomedical endoscopic applications
Creators: name: Hopkinson, Charlotte
Publisher: name: The University of Edinburgh
Year: 2025
Subjects: subject: biomedical endoscopic applications
subject: Endoscopic cameras
subject: Fluorescence lifetime imaging (FLIm)
subject: single photon avalanche diodes (SPADs)
subject: time of flight (ToF) imaging
subject: fluorescence lifetime imaging with distance and ranging (FLImDAR)

description: Endoscopic cameras play a vital role in medical diagnostics as they provide a minimally invasive way to image inside the body. Conventional cameras, however, are reliant on the use of white light which does not offer any additional diagnostic information over cues from colour and intensity. Fluorescence lifetime imaging (FLIm) is a technique that can enhance endoscopy by providing differentiation between tissue types without the need for biomarkers. This could be particularly valuable, for example, in the identification of cancerous tissue margins pre-intervention. Time resolved arrays which incorporate single photon avalanche diodes (SPADs) are a prime candidate for FLIm as they offer very fast and precise measurements of individual photon arrival times. In addition, they are able to obtain high speed images, even in low light conditions such as typically observed in FLIm of endogenous fluorophores in the human body. Another time resolved technique enabled by SPADs is time of flight (ToF) imaging which allows the distance to a target to be determined. ToF based distance mapping could provide crucial depth perception which FLIm images inherently lack. In the case of endoscopic imaging, this allows for greater camera and instrument control which in turn mitigates the risk of tissue damage during surgical procedures. This research presents a combined fluorescence lifetime imaging with distance and ranging (FLImDAR) technique, realised through the use of SPAD arrays. The FLImDAR modality has strong applications in clinical endoscopic imaging and thus is the focus of this research. Similar previous studies have investigated depth measurements using deep tissue fluorescence which requires the addition of fluorescent dyes. This work, however, targets surface auto-fluorescence. Firstly, a computational model is used to examine and refine various algorithms which can be implemented to perform FLImDAR. This model is used to decide the final FLImDAR technique, as well as investigate the impact of signal noise. Next, FLImDAR is demonstrated experimentally using fluorescent polymer targets. Three SPAD sensors (MegaFrame, Quanticam and Endocam) are tested for compatibility with the FLImDAR modality, each showcasing different strengths and limitations. To further prove FLImDAR’s ability to perform in low photon level auto-fluorescent applications, ovine and cancerous human pulmonary targets are imaged. The final part of this study regards performing FLImDAR with a miniaturised imaging system. The SPAD sensor, Endocam, is characterised prior to integration into a handheld camera. Using the handheld camera, FLIm videos of ovine tissue are captured as well as long exposure FLImDAR images. With further advances in detectors, sensor architecture and photon budgets, this research indicates the significant performance improvements that will enable practical clinical application of the FLImDAR technique.