New approach for an optical biopsy in melanoma diagnostics

恶性黑色素瘤是最危险的皮肤癌，死亡率最高。自20世纪80年代以来，发病率增加了两倍多。该项目解决了黑色素瘤诊断的现有缺陷。对于可疑的皮肤病变，通常不清楚是良性还是恶性。肿瘤的厚度，即黑色素瘤细胞的浸润深度，是评估肿瘤分期和疾病预后的决定性标准。这也决定了进一步的治疗。根据目前的金标准，黑色素瘤的可靠诊断和实际厚度的确定只有通过组织病理学才能实现。可靠、及时和非侵入性的诊断目前还不可能，但这将标志着黑色素瘤诊断的明显改善和范式转变。该项目的总体目标是开发一种新的综合设备，该设备将首次能够在术前确定(i)侵袭深度和（ii）可疑黑色素瘤皮肤病变的尊严，从而得出可靠的诊断。为了获得所有相关信息，三种光学模式-光学相干断层扫描（OCT），光声学（OA）和拉曼光谱(RS) -将首次在多模态设备中结合，探索可接近的皮肤参数并评估其诊断能力。此外，将建立相关的智能、自动化评估程序，并在临床的小鼠和患者测量中验证其功能。该项目的挑战是：(i)通过三种模式的组合实现快速（<15分钟）成像系统，（ii）使用OCT和OA可靠地确定病变的浸润深度（OCT高达1.5 mm， OA为几mm），具有相似的分辨率（<15 μm和<30 μm，分别），（iii）通过OCT（形态学）和RS（化学成分）确定病变的尊严，具有高灵敏度（> 90%）和特异性（> 70%）。以及（iv）依赖于生成的数据库的评估算法的实施，该数据库将通过多变量数据分析、3D分割和深度学习算法实现忠实和快速的病变确定。在拟议的3年资助期结束时，将展示和验证新设备在确定黑色素瘤侵袭深度和尊严方面的适用性。该多模态系统首次确保了在黑色素瘤诊断中具有高灵敏度和特异性的光学活检。在第二个可能的2年资助期内，该设备的适用性将在临床试验研究中进行评估。此外，还可以研究确定其他皮肤病（即炎症性皮肤病和不同类型的皮肤癌）的诊断标准以及疾病进展和黑色素瘤治疗研究的潜力。

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.