Optical clearing method for monitoring cutaneous microcirculation response to vasoactive drugs with high sensitivity

摘要

Laser speckle contrast imaging technique has been playing an important role in monitoring cutaneous microcirculation, but the strong scattering of skin restricts the imaging depth and contrast, and also makes it impossible to assess the cutaneous microcirculation response dynamically with high sensitivity. The tissue optical clearing is helpful for opening a visible window on mouse dorsal skin. In this work, the cutaneous microcirculation response to vasoactive noradrenaline is monitored with the laser speckle contrast imaging system before and after skin optical clearing. The results show that the optical clearing method can significantly enhance the contrast of laser speckle contrast imaging, and small blood vessels whose diameter less than 20μm can be distinguished with high resolution. The dynamic changes in cutaneous microvascular diameter and blood flow velocity caused by drug can be monitored sensitively. In contrast, it is difficult to detect the cutaneous microcirculation response that occurred in the blood vessels more than 100μm in the intact skin, and the signal-to-noise ratio is too low to monitor the dynamic changes caused by the same drug. Thus, skin optical clearing method can enhance the ability of laser speckle contrast imaging in accessing cutaneous microcirculation response, including the imaging contrast, resolution and sensitivity.