Cao Rui, Li Jun, Ning Bo, Sun Naidi, Wang Tianxiong, Zuo Zhiyi, Hu Song
Department of Biomedical Engineering, University of Virginia, VA 22908, USA.
Department of Anesthesiology, University of Virginia, VA 22908, USA.
Neuroimage. 2017 Apr 15;150:77-87. doi: 10.1016/j.neuroimage.2017.01.049. Epub 2017 Jan 20.
A long-standing challenge in optical neuroimaging has been the assessment of hemodynamics and oxygen metabolism in the awake rodent brain at the microscopic level. Here, we report first-of-a-kind head-restrained photoacoustic microscopy (PAM), which enables simultaneous imaging of the cerebrovascular anatomy, total concentration and oxygen saturation of hemoglobin, and blood flow in awake mice. Combining these hemodynamic measurements allows us to derive two key metabolic parameters-oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO). This enabling technology offers the first opportunity to comprehensively and quantitatively characterize the hemodynamic and oxygen-metabolic responses of the mouse brain to isoflurane, a general anesthetic widely used in preclinical research and clinical practice. Side-by-side comparison of the awake and anesthetized brains reveals that isoflurane induces diameter-dependent arterial dilation, elevated blood flow, and reduced OEF in a dose-dependent manner. As a result of the combined effects, CMRO is significantly reduced in the anesthetized brain under both normoxia and hypoxia, which suggests a mechanism for anesthetic neuroprotection. The head-restrained functional and metabolic PAM opens a new avenue for basic and translational research on neurovascular coupling without the strong influence of anesthesia and on the neuroprotective effects of various interventions, including but not limited to volatile anesthetics, against cerebral hypoxia and ischemia.
光学神经成像领域长期以来面临的一项挑战是在微观层面评估清醒啮齿动物大脑中的血流动力学和氧代谢情况。在此，我们报告了首例头部固定光声显微镜（PAM），它能够对清醒小鼠的脑血管解剖结构、血红蛋白的总浓度和氧饱和度以及血流进行同步成像。结合这些血流动力学测量结果，我们能够得出两个关键的代谢参数——氧摄取分数（OEF）和脑氧代谢率（CMRO）。这项使能技术首次提供了全面且定量地表征小鼠大脑对异氟烷（一种广泛应用于临床前研究和临床实践的全身麻醉剂）的血流动力学和氧代谢反应的机会。对清醒和麻醉状态下大脑的并行比较显示，异氟烷会以剂量依赖的方式诱导直径依赖性动脉扩张、血流量增加以及OEF降低。由于这些综合效应，在常氧和低氧条件下，麻醉状态下的大脑CMRO均显著降低，这提示了一种麻醉神经保护机制。头部固定的功能和代谢PAM为神经血管耦合的基础研究和转化研究开辟了一条新途径，避免了麻醉的强烈影响，并可研究包括但不限于挥发性麻醉剂在内的各种干预措施对脑缺氧和缺血的神经保护作用。
