Experimental characterization of light penetration in animals and human-head simulation for photocatalytic therapy in the brain

Photoexcitation of chemical compounds, together with the light transmittance of the biological window, enables targeted phototherapy. We have developed a photocatalyst-based therapeutic approach for Alzheimer disease and demonstrated amyloid-β reduction in a mouse model. However, it is unclear whether sufficient light energy can be delivered transcranially to target amyloid fibrils in the brains of larger animals, such as humans. Therefore, in this study, we measured the light energy from the body surface, through the skull, to the brain in mice in vivo and in dog head specimens in mortua , focusing on the short-wavelength side of the biological window. We then constructed an optical simulation model based on these measurements, and estimated the light energy reaching the brain from the human body surface. Our results show that only a small fraction of the light applied to the human body surface reaches the brain, with most energy loss occurring in the skin. In contrast, attenuation by the skull was relatively modest. These findings suggest that sufficient light energy can be delivered to the human brain surface through an appropriately designed delivery route and device that bypasses the skin, supporting the translational potential of photocatalytic therapy.