Intraoperative Diagnosis of Bladder Tumors Using Protoporphyrin IX (PpIX) Fluorescence Lifetime
Ivan D. Filippov1, A. Hasan1,5, Gleb S. Budylin2, D. O. Suverneva1, Denis A. Davydov1,2, Nadezhda V. Korneva6, Dmitry A. Kislyakov3, Vladislav I. Shcheslavskiy4, Evgeny A. Shirshin1,2; 1Lomonosov Moscow State University, Moscow, Russia; 2I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; 3Voskresensk Hospital, Voskresensk, Moscow Region, Russia; 4Privolzhsky Research Medical University, Nizhny Novgorod, Russia; 5VPG LaserONE LLC, Fryazino, Moscow Region, Russia; 6Lomonosov University Clinic, Moscow, Russia
Abstract
Bladder cancer poses a challenge in urologic oncology. White-light cystoscopy remains the standard method for detecting bladder tumors; however, its sensitivity is limited, particularly for flat or subtle lesions. Photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) improves lesion contrast through preferential accumulation of protoporphyrin IX (PpIX) in tumor cells and detection of red fluorescence. Despite its high sensitivity, PDD specificity may be reduced by PpIX accumulation in injured, non-neoplastic tissue.
To improve specificity, this study investigated PpIX fluorescence lifetime, a parameter less affected by excitation intensity, detection geometry, and tissue optics and sensitive to the fluorophore microenvironment. A fiber-optic system based on time-correlated single-photon counting (TCSPC) was developed to record fluorescence decay curves. Ex vivo measurements were performed on resected tumor, normal, and inflamed bladder tissue, with histopathology as the reference standard. The decays were fitted with a biexponential model to determine the lifetime of the long-lived component (τ₂) and the amplitude ratio of the long- to short-lived components (a₂/a₁).
Tumor tissue exhibited higher values of both parameters than normal tissue and inflamed samples. The system was modified to enable fluorescence acquisition under surgical illumination, and in vivo measurements were performed within the bladder. The in vivo results reproduced the ex vivo trends and support the combined use of τ₂ and a₂/a₁ for intraoperative discrimination between tumor and non-neoplastic tissue.
Speaker
Filippov Ivan
Lomonosov Moscow State University, Faculty of Physics
Russia
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