Significance: Cerebrovascular reactivity (CVR), defined as the ability of the cerebral vasculature to dilate or constrict in response to a vasoactive stimulus, is an important indicator of the brain’s vascular health. However, mechanisms of cerebrovascular dysregulation are poorly understood, and no effective treatment strategies for impaired CVR exist. Preclinical murine models provide an excellent platform for interrogating mechanisms underlying CVR dysregulation and determining novel therapeutics that restore impaired CVR. However, quantification of CVR in mice is challenging. Aim: We present means of assessing CVR in awake mice using intraperitoneal injection of acetazolamide (ACZ) combined with continuous monitoring of cerebral blood flow. Approach: Measurements of cerebral blood flow were made with a minimally invasive diffuse correlation spectroscopy sensor that was secured to an optical window glued to the intact skull. Two source–detector separations (3 and 4.5 mm) per hemisphere were used to probe different depths. CVR was quantified as the relative increase in blood flow due to ACZ. CVR was assessed once daily for 5 days in 5 mice. Results: We found that CVR and the response half-time were remarkably similar across hemispheres and across 3- versus 4.5-mm separations, suggesting a homogenous, whole brain response to ACZ. Mean(std) intra- and intermouse coefficients of variations were 15(9)% and 19(10)%, respectively, for global CVR and 24(15)% and 27(11)%, respectively, for global response half-time. Conclusion: In sum, we report a repeatable method of measuring CVR in free-behaving mice which can be used to screen for impairments with disease and to track changes in CVR with therapeutic interventions.

中文翻译：

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使用弥散相关光谱法在清醒小鼠中测量脑血管反应性

意义：脑血管反应性（CVR）是大脑血管系统响应血管活性刺激而扩张或收缩的能力，是大脑血管健康的重要指标。然而，人们对脑血管失调的机制了解甚少，并且不存在针对CVR受损的有效治疗策略。临床前鼠模型为研究CVR失调的潜在机制和确定恢复受损CVR的新疗法提供了一个极好的平台。但是，小鼠中CVR的定量分析具有挑战性。目的：我们提出了通过腹膜内注射乙酰唑胺（ACZ）与连续监测脑血流来评估清醒小鼠中CVR的方法。方法：用微创扩散相关光谱传感器对脑血流量进行测量，该传感器固定在粘贴在完整颅骨上的光学窗上。每个半球使用两个源-探测器间隔（3和4.5 mm）来探测不同的深度。CVR被量化为由于ACZ引起的血流量的相对增加。在5只小鼠中每天一次评估CVR，持续5天。结果：我们发现半球，3毫米和4.5毫米间距之间的CVR和半衰期反应非常相似，这表明全脑对ACZ的反应是均匀的。全局CVR的平均（std）鼠标内和鼠标间变异系数分别为15（9）％和19（10）％，全局响应半时分别为24（15）％和27（11）％ 。结论：总而言之，