ABSTRACT Significance Photoacoustic imaging (PAI) provides contrast based on the concentration of optical absorbers in tissue, enabling the assessment of functional physiological parameters such as blood oxygen saturation (sO 2 ). Recent evidence suggests that variation in melanin levels in the epidermis leads to measurement biases in optical technologies, which could potentially limit the application of these biomarkers in diverse populations. Aim To examine the effects of skin melanin pigmentation on photoacoustic imaging and oximetry. Approach We evaluated the effects of skin tone in PAI using a computational skin model, two-layer melanin-containing tissue-mimicking phantoms, and mice of a consistent genetic background with varying pigmentations. The computational skin model was validated by simulating the diffuse reflectance spectrum using the adding-doubling method, allowing us to assign our simulation parameters to approximate Fitzpatrick skin types. Monte Carlo simulations and acoustic simulations were run to obtain idealised photoacoustic images of our skin model. Photoacoustic images of the phantoms and mice were acquired using a commercial instrument. Reconstructed images were processed with linear spectral unmixing to estimate blood oxygenation. Linear unmixing results were compared with a learned unmixing approach based on gradient-boosted regression. Results Our computational skin model was consistent with representative literature for in vivo skin reflectance measurements. We observed consistent spectral colouring effects across all model systems, with an overestimation of sO 2 and more image artefacts observed with increasing melanin concentration. The learned unmixing approach reduced the measurement bias, but predictions made at lower blood sO 2 still suffered from a skin tone-dependent effect. Conclusion PAI demonstrates measurement bias, including an overestimation of blood sO 2 , in higher Fitzpatrick skin types. Future research should aim to characterise this effect in humans to ensure equitable application of the technology.

The effects of skin tone on photoacoustic imaging and oximetry