Enhanced ability of LSCI for monitoring blood flow dynamics in vivo with tissue optical clearing method Rui Shi, Yang Zhang, Yanjie Zhao, Dan Zhu* Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China Department of Biomedical Engineering, Key Laboratory of Biomedical Photonics of Ministry of Education, Huazhong University of Science and Technology, Wuhan 430074, China *dawnzh@mail.hust.edu.cn Abstract: Laser speckle contrast imaging (LSCI) has shown a significant potential in monitoring the microcirculation. But the strong scattering of tissue tremendously restricts the imaging resolution and contrast, which makes it difficult to assess the blood flow dynamics with high sensitivity. The tissue optical clearing techniques present a new opportunity to decrease the scattering, and dramatically enhance the ability of LSCI. During the past years, both skin optical clearing and skull optical clearing methods had been developed, which significantly enhanced the imaging resolution and contrast. In this work, the cutaneous and cerebral microvascular dynamic responses to vasoactive drug were monitored using LSCI combined with the tissue optical clearing methods. The results showed that the optical clearing methods made it possible for LSCI to assess the microvascular dynamic responses caused by drug with superior sensitivity. Comparing the dynamic changes in cutaneous with cerebral microcirculation, it can be found that the cerebral blood flow had a faster and stronger response than cutaneous blood flow. Thus, optical clearing method will play a significant role for LSCI in monitoring the microcirculation and their dynamic changes caused by some vascular diseases, such as tumor and diabetes mellitus. Keywords: laser speckle contrast imaging, tissue optical clearing, blood flow dynamics, vasoactive drug