New approach for an optical biopsy in melanoma diagnostics

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Malignant melanoma is the most dangerous type of skin cancer and has the highest mortality rate. Since the 1980s, the incidence rate has more than tripled. This project addresses an existing deficit in melanoma diagnostics. For a suspicious skin lesion it is often not clear whether it is malignant or benign. The tumor thickness, i.e. the depth of invasion of melanoma cells, is the decisive criterion apart from the dignity (malignant or benign) for assessing the tumor stage and the prognosis of the disease. It also determines the further treatment. According to the current gold standard, a reliable diagnosis of melanoma and the determination of the actual thickness are only possible by histopathology. Reliable, timely and non-invasive diagnostics are currently not possible, but would signify a clear improvement and initiate a paradigm shift in melanoma diagnostics.The overall goal of this project is the development of a new, integrative device that will enable the determination of both (i) the invasion depth and (ii) the dignity of suspected melanoma skin lesions preoperatively, for the first time, leading to reliable diagnosis. To obtain all relevant information, three optical modalities - optical coherence tomography (OCT), optoacoustics (OA) and Raman spectroscopy (RS) - will be combined for the first time in a multimodal device, the accessible skin parameters explored and their diagnostic capability evaluated. Also, the associated intelligent, au-tomated evaluation procedures will be established and the functionality validated in mouse and patient measurements in the clinic.The challenges of the project are (i) the realization of a fast (< 15 min) imaging system through combination of the three modalities, (ii) the reliable determination of the invasion depth of lesions using OCT and OA (up to 1.5 mm with OCT and several mm with OA) with similar resolution (<15 μm and <30 μm, resp.), (iii) the determination of lesion dignity by OCT (morphology) and RS (chemical composition) with high sensitivity (> 90%) and specificity (> 70%), and (iv) the implemen-tation of evaluation algorithms relying on generated data bases that will enable faithful and rapid lesion determination by multivariate data analysis, 3D segmentation, and deep learning algorithms.At the end of the proposed 3 year funding period, the suitability of the new device with regard to determination of invasion depth and dignity of melanoma will be demonstrated and validated. The multimodal system should ensure, for the first time, an optical biopsy in melanoma diagnosis with high sensitivity and specificity. In a potential second 2-year funding period, the suitability of the device shall be evaluated in a clinical pilot study. Also the potential with regard to identification of diagnostic criteria for other skin diseases, i.e. inflammatory skin diseases and different skin cancer types, as well as disease progression and melanoma therapy studies can be investigated.