Abstract
We demonstrate that structured illumination microscopy has the potential to enhance fluorescence lifetime imaging microscopy (FLIM) as an early detection method for oral squamous cell carcinoma. FLIM can be used to monitor or detect changes in the fluorescence lifetime of metabolic cofactors (e.g. NADH and FAD) associated with the onset of carcinogenesis. However, out of focus fluorescence often interferes with this lifetime measurement. Structured illumination fluorescence lifetime imaging (SI-FLIM) addresses this by providing depth-resolved lifetime measurements, and applied to oral mucosa, can localize the collected signal to the epithelium. In this study, the hamster model of oral carcinogenesis was used to evaluate SI-FLIM in premalignant and malignant oral mucosa. Cheek pouches were imaged in vivo and correlated to histopathological diagnoses. The potential of NADH fluorescence signal and lifetime, as measured by widefield FLIM and SI-FLIM, to differentiate dysplasia (pre-malignancy) from normal tissue was evaluated. ROC analysis was carried out with the task of discriminating between normal tissue and mild dysplasia, when changes in fluorescence characteristics are localized to the epithelium only. The results demonstrate that SI-FLIM (AUC = 0.83) is a significantly better (p-value = 0.031) marker for mild dysplasia when compared to widefield FLIM (AUC = 0.63).
Highlights
We demonstrate that structured illumination microscopy has the potential to enhance fluorescence lifetime imaging microscopy (FLIM) as an early detection method for oral squamous cell carcinoma
Prognostic outcomes can be improved by early detection of the disease, nearly 70% of all oral cancers are diagnosed in advanced disease stages where the 5-year survival rate drops dramatically to 39%1
The aims of the present study were to investigate structured illumination fluorescence lifetime imaging microscopy (SI-FLIM) as a screening method for early stages of premalignant lesions, and to show that SIFLIM is superior in this regard when compared to widefield FLIM on its own
Summary
We demonstrate that structured illumination microscopy has the potential to enhance fluorescence lifetime imaging microscopy (FLIM) as an early detection method for oral squamous cell carcinoma. The potential of NADH fluorescence signal and lifetime, as measured by widefield FLIM and SI-FLIM, to differentiate dysplasia (pre-malignancy) from normal tissue was evaluated. The current standard to screen for oral cancer is via a visual examination of the oral cavity by a trained clinician with subsequent tissue removal and histopathological analysis, if a suspicious lesion is identified[5]. There are two major problems with the current screening method: first is the inherent time delay between the identification of a potentially malignant lesion and its accurate histopathological diagnoses; second is that suspicious oral cancer lesions are often diffuse and multi-focal, which makes screening the oral cavity even more challenging. There is a tremendous need for a screening tool that can accurately and quickly diagnose malignant and premalignant lesions within the mouth
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