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Optical Biopsy for Tissue Diagnostics of Squamous Cell Carcinoma in the Upper Aerodigestive Tract using Confocal Laser Endomicroscopy Imaging

Subject Area Otolaryngology, Phoniatrics and Audiology
Image and Language Processing, Computer Graphics and Visualisation, Human Computer Interaction, Ubiquitous and Wearable Computing
Dentistry, Oral Surgery
Term from 2020 to 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 439264659
 
Final Report Year 2024

Final Report Abstract

Confocal Laser Endomicroscopy (CLE) is an optical imaging method utilizing laser light to image superficial tissue. It uses fluorescein as contrast agent, which is distributed to the tissues microcirculation, intercellular spaces and cytoplasmic components, thus enabling visualization and structural analysis of cellular tissue as well as abnormal patterns of microvasculature of mucous membranes of the human organism. These visible mucosal changes are usually present in tumor tissue, i.e., also in the head and neck region. The heterogeneous group of head and neck cancers affects more than 2.5 million people and causes 379,000 deaths per year worldwide. In the oral cavity and pharynx, squamous cell carcinoma (SCC) accounts for over 90 percent of all cancer types, as well as for almost 100 percent of malignancies in the larynx. More than two-thirds of all patients with head and neck cancer are diagnosed at an advanced tumor stage, which reduces treatment options and increases radicality of treatment and mortality. At present the gold standard of diagnosis is an invasive tissue biopsy with subsequent histopathological assessment. However, biopsies carry the risk of infection, bleeding and tissue damage (with functional limitations). In addition, during surgical therapy (tumor resection), safe margins must be proved by biopsying a cuff of healthy tissue around the tumor. CLE could provide a ’real-time’ optical biopsy avoiding unnecessary biopsies, reducing the amount of healthy tissue removed and enable biopsies in previously unsuspected regions for early tumor detection. With this project we investigated the value of CLE in oral, pharyngeal and laryngeal mucosa. It was shown that CLE is a suitable method for differentiating squamous cell carcinoma from physiological mucosa in the oral cavity, pharynx and larynx. The evaluation was possible for both CLE experts and inexperienced evaluators with developed and validated evaluation criteria (and scoring systems). Physiological differences in the composition of the mucous membranes (of the head and neck region) could be visualized for the first time and taken into account when making a diagnosis. Morphological characteristics, such as tissue homogeneity, cellular structure, blood vessel morphology, the ratio of nucleus to cytoplasm and cell clusters were identified as meaningful and taken into account. This enables in-vivo diagnosis and intraoperative determination of resection margins, which, although not yet able to replace frozen section analysis, offers the potential for more targeted biopsies, thereby preserving healthy tissue. The automatic classification of the generated video database was advanced within the project and a robust automatic artifact detection was developed and established. The present results are promising for future non-invasive and early diagnosis of carcinomas of the head and neck regions.

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