In vivo local fluorescence spectroscopy in PDD of superficial bladder cancer

Abstract

Objective: A combination of fluorescence imaging with in vivo local fluorescence spectroscopy (LFS) was used to improve the predictive ability of photodynamic diagnosis (PDD) of superficial bladder cancer after intravesical instillation of Alasense, a 5-aminolevulinic acid (5-ALA)-based agent. Material and method: A total of 62 patients with superficial malignancies of the urinary bladder were included in a preliminary clinical study. Nineteen patients underwent autofluorescence (AF) examination, whereas 43 patients underwent photodynamic diagnosis (PDD) after intravesical instillation of Alasense (NIOPIK, Russia). After visual examination of the urinary bladder wall under white and blue light, fluorescence emission spectra were recorded in vivo under 442 and 532 nm laser excitation within visible red fluorescent zones that had been preliminarily revealed by fluorescence imaging. For spectral data interpretation, a spectral fluorescence parameter was introduced as a ratio of the 5-ALA-induced protoporphyrin IX-emission intensity to that of the AF emission. In the search for a quantitative criterion for this parameter, as well as a diagnostic algorithm to facilitate differentiation between inflammatory and neoplastic tissues, two approaches were tested based on: (1) a posteriori estimation of the threshold values of the spectral fluorescence parameters for inflammation and cancerous tissues, and (2) a posteriori probability of attributing an acquired emission spectrum to a histologically confirmed tissue type. Results: In the group of patients without intravesical instillation of Alasense (n=19), LFS showed a dramatic drop (with a factor of 5-20, p<0.0001) in the AF emission intensity of superficial bladder malignancies under 442 and 532 nm laser excitation, although no reliable distinction was revealed in the AF emission intensity between normal urothelium and inflammatory foci. In the group of patients with intravesical instillation of Alasense (n=43), false positive (FP) results were confirmed histologically in 18 of 54 fluorescent foci revealed by fluorescence imaging, and the positive predictive value (PPV) was estimated to be 67%. Correlations of the spectral fluorescence parameter with the histological results were studied and probability distribution functions (PDFs) of this parameter were constructed for normal urothelium (type I), inflammation, papilloma, low-grade dysplasia (type II), as well as high-grade dysplasia, CIS and TCC (type III) at both excitation wavelengths. PDF distributions for "inflammation - neoplasia" were shown to have essential overlaps, causing certain problems in definition of the thresholds of the spectral fluorescence parameters and attribution of the recorded spectra to the three tissue types. Despite this, the threshold-based approach allowed for a reduction in the number of FP cases to 3 and an increase of the PPV to 91%. In another approach, the maximum realization probabilities of the spectral fluorescence parameter were selected as criteria for attribution of the tested tissue to one of the histological tissue types. Estimations based on this approach showed that the probability of FP cases and the PPV could be roughly estimated as 0-0.1 and as 91-100% at λex=442 and 532 nm respectively. Conclusion: This preliminary clinical study shows that both approaches allow for a significant increase in the PPV of PDD of superficial bladder cancer. Therefore the combination of fluorescence imaging with in vivo LFS may be helpful for minimizing false-positive fluorescence and reducing the number of biopsies necessary. © 2009 Elsevier GmbH. All rights reserved.