noninvasive optical measurement of cerebral blood flow in mice using molecular dynamics analysis of indocyanine green非侵入式光学测量脑血流量的吲哚菁绿的老鼠使用分子动力学分析.pdfVIP

Noninvasive Optical Measurement of Cerebral Blood Flow in Mice Using Molecular Dynamics Analysis of Indocyanine Green 1 1,2,3 Taeyun Ku , Chulhee Choi * 1 Graduate School of Medical Science and Engineering, KAIST, Daejeon, Republic of Korea, 2 Department of Bio and Brain Engineering, KAIST, Daejeon, Republic of Korea, 3 KI for the BioCentury, KAIST, Daejeon, Republic of Korea Abstract In preclinical studies of ischemic brain disorders, it is crucial to measure cerebral blood flow (CBF); however, this requires radiological techniques with heavy instrumentation or invasive procedures. Here, we propose a noninvasive and easy-to-use optical imaging technique for measuring CBF in experimental small animals. Mice were injected with indocyanine green (ICG) via tail-vein catheterization. Time-series near-infrared fluorescence signals excited by 760 nm light-emitting diodes were imaged overhead by a charge-coupled device coupled with an 830 nm bandpass-filter. We calculated four CBF parameters including arrival time, rising time and mean transit time of a bolus and blood flow index based on time and intensity information of ICG fluorescence dynamics. CBF maps were generated using the parameters to estimate the status of CBF, and they dominantly represented intracerebral blood flows in mice even in the presence of an intact skull and scalp. We demonstrated that this noninvasive optical imaging technique successfully detected reduced local CBF during middle cerebral artery occlusion. We further showed that the proposed method is sufficiently sensitive to detect the differences between CBF status in mice anesthetized with either isoflurane or ketamine–xylazine, and monitor the dynamic changes in CBF after reperfusion during transient middle cerebral artery occlusion. The near-infr