Two diagnostic criteria of optical spectroscopy for bladder tumor detection: Clinical study using 5-ALA induced fluorescence and mathematical modeling

Background: The study proposes to improve bladder cancer diagnosis by photodynamic diagnosis (PDD) using red-light excitation (632.8 nm) of 5-ALA induced-protoporphyrin IX. Employing 9 patients' bladders, two types of signals were used to improve diagnostic accuracy for malignancy and we also present numerical modeling of the scattering coefficient to provide biological explanation of the results obtained. Methods: Two modalities of bladder cancer spectral diagnosis are presented: conventional PDD and intensity assessment of the diffusely reflected laser light by fiber-optic spectroscopy. Experiments are done in clinical conditions and as a series of numerical simulations. Results: High-grade cancerous bladder tissues display twice a higher relative fluorescence intensity (mean value 1, n = 9) than healthy (0.39, n = 9), dysplastic (0.44, n = 5) tissues and CIS (0.39, n = 2). The laser backscattering signal allows to discriminate most effectively high-grade cancerous and dysplastic tissues from normal. Numerical modeling of diffuse reflectance spectra reveals that spectral behavior of the back-scattered light depends on both, nuclear size and nuclear density of tumoral cells. Conclusions: Unlike the fluorescence signal, where its value is higher in the case of pathological tissues, the tendency of the laser signal to, both, decrease or increase in comparison with the signal from normal urothelium, should be perceived as a sign towards neoplasm. Numerical simulation reveals that such a double-analysis at a multiwavelength mode potentially may be used to provide diagnostic accuracy.