Endoscopic Fluorescence Imaging : Spectral Optimization and in vivo Characterization of Positive Sites by Magnifying Vascular Imaging

Since several decades, the physicians are able to access hollow organs with endoscopic methods, which serve both as diagnostic and surgical means in a wide range of disciplines of the modern medicine (e.g. urology, pneumology, gastroenterology). Unfortunately, white light (WL) endoscopy displays a limited sensitivity to early pre-cancerous lesions. Hence, several endoscopic methods based on fluorescence imaging have been developed to overcome this limitation. Both endogenous and exogenously-induced fluorescence have been investigated, leading to commercial products. Indeed, autofluorescence bronchoscopy, as well as porphyrin-based fluorescence cystoscopy, are now on the market. As a matter of fact, fluorescence-based endoscopic detection methods show very high sensitivity to pre-cancerous lesions, which are often overlooked in WL endoscopy, but they still lack specificity mainly due to the high false-positive rate. Although most of these false positives can easily be rejected under WL observation, tissue abnormalities such as inflammations, hyperplasia, and metaplasia are more difficult to identify, often resulting in supplementary biopsies. Therefore, the purpose of this thesis is to study novel, fast, and convenient method to characterize fluorescence positive spots in situ during fluorescence endoscopy and, more generally, to optimize the existing endoscopic setup. In this thesis, several clinical evaluations were conducted either in the tracheo-bronchial tree and the urinary bladder. In the urinary bladder, fluorescence imaging for detection of non-muscle invasive bladder cancer is based on the selective production and accumulation of fluorescing porphyrins, mainly protoporphyrin IX (PpIX), in cancerous tissues after the instillation of Hexvix® during one hour. In this thesis, we adapted a rigid cystoscope to perform high magnification (HM) cystoscopy in order to discriminate false from true fluorescence positive findings. Both white light and fluorescence modes are possible with the magnification cystoscope, allowing observation of the bladder wall with magnification ranging between 30× – for standard observation – and 650×. The optical zooming setup allows adjusting the magnification continuously in situ. In the high magnification regime, the smallest diameter of the field of view is 600 microns and the resolution is 2.5 microns, when in contact with the bladder wall. With this HM cystoscope, we characterized the superficial vascularization of the fluorescing sites in WL (370–700 nm) reflectance imaging in order to discriminate cancerous from non-cancerous tissues. This procedure allowed us to establish a classification based on observed vascular patterns. 72 patients subject to Hexvix® f luorescence cystoscopy were included in the study. Comparison of HM cystoscopy classification with histopathology results confirmed 32/33 (97%) cancerous biopsies, and rejected 17/20 (85%) non-cancerous lesions. No vascular alteration could be observed on