Nonlinear Optical Microscopy for Melanoma: Challenges, Tools and Opportunities

The natural pigments known as melanins are thought to play a role in the etiology and progression of melanoma, but many of their roles are currently not well understood. While quantification of melanins have, up until now, have been performed in bulk tissue ex vivo, new imaging technologies have unlocked the means to visualize and quantify melanins at the sub-cellular scale. The nonlinear imaging methods known as pump-probe, coherent Raman, and sum-frequency absorption microscopies provide subcellular resolution imaging of melanins, enabling label-free, longitudinal quantification of both eumelanin and pheomelanin in situ and in vivo. These nonlinear imaging toolkits have been well proven in both animal models and human samples, moving them tantalizingly close to clinical application. Future efforts integrating these tools into practical, mobile imaging systems will provide immense benefit both to clinical research and practice.