Topical Application of Tartrazine for Enhanced Visualization of Subcutaneous Structures in Dermatology

Optical imaging of biological tissues is limited by unwanted scattering and absorption of light, which restricts both the depth of imaging and the spatial resolution. This scattering occurs due to refractive index (RI) mismatches between different tissue components, such as the low RI of water-rich cytosol and the high RI of lipid-based structures. Current methods to reduce light scattering, such as the use of optical clearing agents (OCAs), often involve toxic chemicals or removal of tissue components, making them unsuitable for live imaging.

A recently published study in Science demonstrated that tartrazine, a commonly utilized food dye, is a potent OCA that achieves temporary optical transparency in living tissues. In rodent models, tartrazine was topically administered in a 0.6 M solution and showed reversible transparency effects and rendered their skin, muscle and connective tissues transparent while also providing high-resolution imaging down to the micrometer level without causing tissue damage. Imaging techniques such as laser speckle contrast imaging revealed clear visualization of cerebral blood vessels and internal organs, without needing to surgically remove tissue. Topical application in rodents caused minimal inflammation as affirmed by histological analysis. Additionally, the dye was rapidly cleared via urine and feces without signs of systemic toxicity, and after application, the dye can be washed out to further reduce exposure.

Compared to additional OCAs, tartrazine diffused through tissues more rapidly and required lower concentrations to achieve the desired transparency, resulting in faster visualization. Unlike conventional agents, tartrazine did not cause side effects such as tissue shrinkage or dehydration, making it a promising alternative for non-invasive imaging. These studies established that tartrazine, a strongly absorbing molecule, can reduce the RI mismatch between water and lipids, effectively minimizing light scattering and improving optical transparency.

Tartrazine, also known as FD&C Yellow No. 5, is a commonly utilized coloring agent found in food products, cosmetics, and medications with approved safety profiles across multiple regulatory bodies, including the US Food and Drug Administration (FDA), Joint Food and Agriculture Organization (FAO) and World Health Organization (WHO) Expert Committee on Food Additives (JECFA), and European Food Safety Authority (EFSA). Although tartrazine has been widely used in food and cosmetics, its clinical use for enhancing reversible skin transparency remains under-explored. The long-standing safety profile of tartrazine, in conjunction with the promising preclinical imaging modulation effects, justifies investigating its efficacy in humans.

Existing optical imaging techniques are limited by penetration depth and high scattering, particularly in vivo. This study aims to fill this gap by using tartrazine to improve visualization in human subjects. The potential benefits of this non-invasive technique for human applications are vast, particularly in dermatology, tumor imaging, and surgical planning. If successful, tartrazine could enable clearer, non-invasive imaging of tumors, vascular lesions, and other subcutaneous structures - providing real-time insights into disease progression and aiding in more accurate medical interventions. This clinical pilot study, with a primary focus on the feasibility of topical tartrazine for improving skin transparency, is built upon the promising results from rodent models and tartrazine's well-established safety profile in humans.