High-resolution, noninvasive imaging of a naturally fluorescent protein in mitochondria provides a look into the ‘health’ of normal and cancerous skin and represents a promising method for disease monitoring and diagnosis.
Mitochondria are specialized cell structures that are responsible for producing energy needed for cell function. Healthy mitochondria frequently undergo dynamic reorganization of their internal networks to carry out their energy-producing activities, and defects in mitochondrial organization have been linked to neurodegenerative and cardiovascular disease, as well as abnormal growths of tissue.
The association of defective mitochondria to multiple forms of pathology make it a good marker for many disease states. Current methods to examine and measure mitochondria are not approved for use in humans and are invasive because they require the removal of tissue from patients.
Multiphoton imaging (MPM), a type of high-resolution imaging that can provide clear images of dense tissue such as skin eliminates the need for excision. MPM has recently been used to monitor and detect forms of skin cancer like basal cell carcinomas by analyzing the mitochondrial enzyme NADH. NADH is a great indicator of mitochondrial health or organization because it plays a key role in energy metabolism and it is a naturally fluorescent molecule. However, the existing technique requires advanced knowledge for the evaluation of lesions and is not applicable to a wide range of them.
In a recent report published in Science Translational Medicine, a group of researchers used MPM to characterize mitochondrial organization in the human epidermis using only the naturally fluorescent properties of NADH. In addition, they demonstrated that the technique can be applied to potential diagnosis of cancerous versus healthy skin. A total of 31 participants, 14 with healthy skin and 17 with diseased skin containing basal cell carcinomas or melanomas, had their skin imaged using MPM. NADH fluorescence was collected from various depths and cells within the skin and analyzed.
The MPM approach was able to successfully and in seconds, non-invasively provide a picture of mitochondrial organization in intact human skin tissue. The results showed that healthy skin had very consistent cell morphology and mitochondrial organization that were both dependent on skin depth, or layer. Mitochondria were more clustered together in deeper layers of the skin. In diseased skin, cell morphology was haphazard, and mitochondria clustering patterns were skin depth-independent.
This study shows that a non-invasive high-resolution MPM imaging technique was successful in identifying differences in mitochondrial organization in healthy and diseased tissue in humans. In cancerous skin, it was observed that the uniform morphology and depth-dependence of mitochondria organization are drastically reduced as cancerous cells invade tissue. This technique holds great promise as a future diagnostic and disease monitoring tool that could enhance current diagnostic criteria for early cancer, which predominantly rely on tissue excision and skilled morphological identification.
Written By: Fiona Wong, PhD