Time-Resolved Fluorescence Spectroscopy as a Diagnostic Technique of Oral Carcinoma

Abstract

Objective To investigate the benefit of using time-resolved, laser-induced fluorescence spectroscopy for diagnosing malignant and premalignant lesions of the oral cavity. Design The carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) was applied to 1 cheek pouch of 19 hamsters. The contralateral pouch and the cheek pouches of 3 hamsters without DMBA exposure served as controls. Setting University of California, Davis. Participants Twenty-two golden/Syrian hamsters. Intervention A nitrogen pulse laser was used to induce tissue autofluorescence between the wavelengths of 360 and 650 nm. Main Outcome Measures Spectral intensities and time-domain measurements were obtained and compared with the histopathologic findings at each corresponding site. Results Spectral intensities and lifetime values at 3 spectral bands (SBs; SB1=380±10 nm; SB2=460±10 nm, and SB3 = 635 ± 10 nm) allowed for discrimination among healthy epithelium, dysplasia, carcinoma in situ, and invasive carcinoma. The lifetime values at SB2 were the most important when distinguishing the lesions using only time-resolved parameters. An algorithm combining spectral fluorescence parameters derived from both spectral and time-domain parameters (peak intensities, average fluorescence lifetimes, and the Laguerre coefficient [zero-order]) for healthy epithelium, dysplasia, carcinoma in situ, and invasive carcinoma provided the best diagnostic discrimination, with 100%, 100%, 69.2%, and 76.5% sensitivity and 100%, 92.2%, 97.1%, and 96.2% specificity, respectively. Conclusions The addition of time-resolved fluorescence-derived parameters significantly improves the capability of fluorescence spectroscopy–based diagnostics in the hamster buccal pouch. This technique provides a potential non-invasive diagnostic instrument for head and neck cancer.

Automated analysis of multimodal fluorescence lifetime imaging and optical coherence tomography data for the diagnosis of oral cancer in the hamster cheek pouch model

“…Also, the fact that using both lifetimes τ 1 /e and τ avg along with intensity results in a statistically higher overall accuracy compared to using either of them with intensity, suggests that using both lifetimes provide a more complete description of the fluorescence decay dynamics. A similar result was reported in [ 18 ], where the authors found highest overall classification accuracy for a combination of intensity, average lifetime and zeroth order Laguerre coefficient features, much like the combination of intensity, τ avg , and τ 1 /e in the present study.…”

“…These results are in agreement with the findings of an earlier study investigating the potential of time-resolved fluorescence measurements for oral cancer in a hamster cheek pouch model [ 18 ], where the authors found that using both intensity and lifetime features as opposed to only intensity features resulted in a significant improvement in the overall classification accuracy. The poor performance of intensity based imaging systems in oral cancer screening has also been reported in several other studies [ 19 , 20 ], where it has been noted that there is lack of substantive evidence to suggest that the use of autofluorescence intensity based imaging system improves the sensitivity and specificity of oral cancer beyond the conventional oral examination.…”

A novel method for fast and robust estimation of fluorescence decay dynamics using constrained least-squares deconvolution with Laguerre expansion

“…As demonstrated by previous studies (Farwell et al , 2010), the fluorescence of cheek pouch under UV excitation primarily originated from collagen in sub-mucosa layer and NADH in cells. This is confirmed by the presence of two emission peaks (390 nm and 460 nm corresponding to collagen and NADH emissions respectively) in integrated intensity spectrum (figure 5a).…”

In vivovalidation of a bimodal technique combining time-resolved fluorescence spectroscopy and ultrasonic backscatter microscopy for diagnosis of oral carcinoma

“…These trends agree with previous studies of the oral carcinoma autofluorescence. 5,7,8,31,32 These results were found to be consistent with anatomical and cellular changes in the epithelium tissue associated with disease progression. Increased epithelium thickness or disruption of the connective tissue results in less collagen, and increased cell proliferation leads to an increase in total NADH content.…”