Dynamic real‐time optical microscopy of oral mucosal lesions using confocal laser endomicroscopy

Abstract

Objectives Confocal laser endomicroscopy (CLE) is a novel non‐invasive point‐of‐care optical biopsy technology that enables real‐time in vivo microscopic visualisation of cellular and tissue architecture. In this study, we assessed the diagnostic accuracy of a hand‐held fluorescence single‐fibre distal‐scanning CLE (fsdCLE) platform for diagnosing oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Materials and Methods Forty‐seven patients presenting with 63 distinct oral mucosal lesions were subjected to optical biopsy using a miniaturised fsdCLE system (ViewnVivo®, Optiscan Imaging Ltd) and topical exogenous acriflavine hydrochloride contrast agent before undergoing tissue biopsy and histopathological consensus review by four pathologists. CLE images were captured in vivo in real‐time during clinical examination and assessed on‐the‐fly for the presence of cellular and architectural features of OED/OSCC offering an instantaneous diagnosis. Predicted optical diagnoses were compared to definitive consensus tissue histopathology. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated for the presence/absence of dysplasia/malignancy on optical biopsy. Percentage agreement, Fleiss' kappa, and intraclass correlation coefficient (ICC) were calculated for each assessment stage during the consensus histopathology process. Results Diagnostic accuracy was extremely high at 88.9%. Other metrics were sensitivity 86.8%, specificity 92%, PPV 94.3% and NPV 82.1%. One hundred percent of carcinoma cases were detected accurately using CLE in the clinic. Conclusion fsdCLE is a highly accurate, easy‐to‐use, rapid and slide‐free point‐of‐care in vivo optical technology for diagnosing OED/OSCC and discriminating between dysplastic and non‐dysplastic pathology. It demonstrates near‐perfect agreement with traditional consensus histopathology without the need for physical tissue biopsy.

Intraoperative in vivo confocal endomicroscopy of the glioma margin: performance assessment of image interpretation by neurosurgeon users

“…This would be particularly interesting from a surgeon’s point of view in that the same person would have the surgical perspective and be able to analyze the pathological results. This is also in line with previous observations that examining CLE images in real time yields better diagnostic performance than storing, reviewing, and interpreting them later ( 10 ). It would thus be advantageous for neurosurgeons using CLE to be experienced and effective interpreters of the CLE images they are acquiring.…”

Intraoperative Assessment of Resection Margin in Oral Cancer: The Potential Role of Spectroscopy

“…Several studies have demonstrated promising results, including a scoring system to classify benign and malignant tissue in the oral cavity, and an exceptionally high sensitivity and specificity [ 123 , 124 , 125 ]. Another study suggested that CLE may supplant or reduce the need for physical tissue biopsy in the management of oral cancer [ 126 ]. Horgan CC et al developed and applied a novel hybrid fiber-optic confocal Raman endomicroscopy system for morpho-chemical tissue imaging and analysis, demonstrating real-time microscopic visualization and simultaneous pointwise label-free biomolecular characterization [ 127 ].…”

Acquisition and annotation in high resolution in vivo digital biopsy by confocal microscopy for diagnosis in oral precancer and cancer

“…Fluorescein and acriflavine can be considered pancytoarchiteral fluorescent agents as they non-selectively bind membrane and nuclear material, regardless of molecular activity. Acriflavine has been used in combination with several types of confocal microscope technology, including point scanning to visualize and diagnose oral mucosal disease ( 18 , 22 ). PARP1 (Poly (ADP-ribose) polymerase 1 is a nuclear protein that has been found to be overexpressed in many malignancies including ovarian cancer, breast cancer and OSCC ( 23 ).…”