FLIM endoscopy for PPIX detection (NIHR)
This project is a collaboration between Imperial College London and Karl Storz GmbH & Co. KG. to investigate the potential of FLIM endoscopy to detect the endogenous photosenstizer, protoporphyrin IX (PPIX), a fluorescent by-product involved in the heme cycle, which is used in photodynamic detection (PDD) of bladder cancer after the application of products such as Hexaminolevulinate (Hexvix)
Professor Paul French (PI)
Dr Daniel Elson (Project manager),
Dr Chris Dunsby,
Professor Mark Neil,
Dr Erik Mayer,
Dr Gordon Kennedy,
Mr Daniel Cohen,
Dr Sergio Coda
Karl Storz Team
Dr Norbert Hansen,
Dr Martin Leonhard
Over the last ten years, fluorescence lifetime imaging (FLIM) has developed from a technique only available to leading instrumentation research laboratories into a technique that is commonly applied to study cellular interactions. This uptake has been motivated by the functional information that becomes available when detecting the lifetimes of different fluorophores, partly due to the sensitivity of fluorescence lifetime to the local environment of the fluorescent molecules. FLIM can be used to detect changes in tissue state caused by diseases such as cancer, atheroma, and osteoarticular arthritis. This is due to the fluorescence lifetime signatures of endogenous fluorophores such as collagen, elastin, NADH, FAD and porphyrins (autofluorescence). It is also possible to use exogenous probes to distinguish disease states, which holds promise for minimally invasive tissue analysis. Whilst there have previously been a few demonstrations of fluorescence lifetime used in endoscopy, the technique has not been developed into a clinically viable system. The objective of this proposal is to create a FLIM endoscope that may be used to detect the lifetime signature of Protoporphyrins IX (PPIX), a fluorescent by-product involved in the heme cycle, which is used in photodynamic detection (PDD) of bladder cancer after the application of products such as Hexaminolevulinate (Hexvix). The objective is to increase detection rates during diagnostic cystoscopy and increase the specificity over standard fluorescence techniques.
The aims are:
1. To develop a modular wide-field fluorescence lifetime imaging system applicable to clinical endoscopy using the Hopkins’ rod lens endoscope system developed at Karl Storz GmbH & Co. KG.
2. To evaluate the improvement in performance when detecting PPIX (e.g. induced by Hexvix) compared with KARL STORZ’s current fluorescence intensity system.
3. To evaluate the performance of the system when imaging fresh tissue samples. We will also put a research ethics application in place for in vivo FLIM for a continuation of this study.
The project partners have extensive experience in FLIM (Imperial) and cystoscopy and PDD (STORZ) and this project will bring together these skills to create a new instrument that will meet the clinical need for higher sensitivity and particularly higher specificity in bladder PDD. The work also has other medical possibilities due to the clinical activity in testing additional PDD agents for other cancers.