Four-modal device comprising optical coherence tomography, photoacoustic tomography, ultrasound, and Raman spectroscopy developed for in vivo skin lesion assessment

The accurate determination of the depth of the infiltration and the pathophysiology is critical to the treatment and excision of skin cancer, particularly melanoma. The current gold standard in skin cancer diagnostics comprises skin biopsy followed by histological examination, which is invasive, time-consuming, and limited in measuring at the deepest level. Non-invasive imaging techniques like dermoscopy, confocal microscopy, and multiphoton microscopy also face limitations in accurately capturing contrast and depth information across lesion locations or distinguishing between malignant and benign tissue. Thus, there is a need for non-invasive techniques capable of obtaining 3D images of skin lesions with sufficiently high spatial resolution, which at the same time assess pathophysiology. To address this problem, we have developed a device that combines optical coherence tomography (OCT), photoacoustic tomography, ultrasound, and Raman spectroscopy into a single scanning unit, enabling the <i>in vivo</i> acquisition of co-localized 3D images and Raman fingerprint spectra of skin lesions with all four modalities under 5 minutes for the whole procedure. We performed measurements on 52 suspicious human skin lesions that were immediately excised following the measurements. The resulting lesion depth exhibited a strong correlation with histological thickness between 0.1-5 mm, achieving a coefficient of determination (R²) of 0.97, which is higher than those from the individual modalities and from previous studies. In addition, the Raman modality offers the possibility to distinguish between malignant and benign lesions. Our results indicate that the developed multimodal approach for 3D imaging and lesion assessment can offer all the required information for non-invasive skin cancer diagnostics. Further clinical measurements are required to determine diagnostic accuracy, which will be performed in the next step in the case of melanoma skin cancer.