Brain Metabolism Monitoring through CCO Measurements Using All-Fiber-Integrated Super-Continuum Source.
Brain Metabolism Monitoring through CCO Measurements Using All-Fiber-Integrated Super-Continuum Source.
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使用全光纤集成超连续源通过 CCO 测量监测脑代谢。
DOI：
10.1117/12.2550137
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Russo,Rachel
中科院分区：
文献类型：
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作者：
Islam,MohammedN;Guo,Kaiwen;Zhai,Tianqu;Memmini,AllyssaK;Martinez,Ramon;Meah,CynthiaN;Kovelman,Ioulia;Weissman,Daniel;Hu,Xiaosu;Kim,Jessica;Broglio,Steven;Beard,Daniel;VANDENBergh,Francoise;Alam,Hasan;Russo,Rachel
为了监测脑震荡、脑功能、器官状况和其他医学应用，需要一种监测组织代谢的非侵入性方法。基于MRI的功能成像技术检测血氧的变化，这与神经活动相关，因此可以预测脑震荡和其他脑外伤的预后。然而，脑代谢紊乱和患者预后之间的潜在关系无法在临床上得到有效利用，因为我们缺乏一种实用的、低成本的、非侵入性的手段来监测急诊科、手术室或医疗机构中的脑氧合和代谢。我们已经开发了一种设备，光学测定细胞色素C氧化酶（CCO），线粒体酶负责的电子传递链的最后一步的氧化还原状态。CCO氧化还原的变化反映了呼吸流量的变化，从而反映了氧化三磷酸腺苷（ATP）合成速率的变化。换句话说，CCO的变化比传统的血氧测量方法更直接地反映脑细胞的代谢活动。为了非侵入性地测量CCO以及血氧的变化，我们开发了细胞色素C氧化酶的超连续红外光谱（SCISCCO）系统，该系统使用全光纤集成的超连续光源来同时测量神经代谢的新（CCO）和传统（血氧）标志物。通过体外测定CCO的近红外光谱，对SCISCCO系统进行了验证。为了证明体内可行性，测量的氧合反应和CCO对急性缺血的反应（例如，血压测试）与来自文献的数据进行比较。此外，我们表明，新设备的测量氧合（HbO）和脱氧（HbR）血红蛋白在屏气的挑战是原则性的，并与以前报道的结果一致。验证SCISCCO系统最后应用于测量大脑氧合和氧化还原状态的CCO在参与者在注意力测试协议。25名健康成年人完成了一项注意力任务，其中包括9个60秒的注意力任务，与60秒的休息基线期交错。已经确定的是，人类大脑的额叶在注意力任务期间是活跃的。因此，我们预测注意力任务应该引起HbO浓度的增加，伴随着CCO氧化还原状态的降低（例如，氧化CCO与还原CCO的比率）。我们的研究结果与我们的预测是一致的：HbO浓度增加，而CCO浓度下降，在注意力块相对于休息基线，从而表明额叶脑区的氧化代谢的增加感兴趣。因此，我们系统的多方法方法验证了新设备及其测量的代谢生物标志物的有效性。SCISCCO系统可能是一种监测大脑和器官代谢的新工具，这对于筛选脑震荡患者或在手术室或急诊室使用以衡量患者对治疗的器官反应可能是非常宝贵的。
For monitoring of concussion, brain function, organ condition and other medical applications, what is needed is a non-invasive method of monitoring tissue metabolism. MRI-based functional imaging technology detects changes in blood oxygenation, a correlate of neural activity, and thus may offer a prediction of prognosis in cases of concussion and other cerebral traumas. Yet, potential relationships between perturbations to cerebral metabolism and patient outcomes cannot be effectively exploited clinically because we lack a practical, low-cost, non-invasive means to monitor cerebral oxygenation and metabolism in the emergency department, operating room, or medical facilities. We have developed a device to optically assay the redox state of Cytochrome-C-Oxidase (CCO), the mitochondrial enzyme responsible for the last step of the electron transport chain. Changes in CCO redox reflect changes in respiratory flux, and thus changes in the rate of oxidative adenosine triphosphate (ATP) synthesis. In other words, changes in CCO reflect brain cell’s metabolic activity more directly than the traditional blood oxygenation measurement methods. To non-invasively measure changes in CCO as well as blood oxygenation, we have developed a SuperContinuum Infrared Spectroscopy of Cytochrome-C-Oxidase (SCISCCO) system that uses an all-fiber integrated, supercontinuum light source to simultaneously measure both of the new (CCO) and the traditional (blood oxygenation) markers of neural metabolism. The SCISCCO system is validated by confirming the near-infrared spectrum of CCO in vitro. To demonstrate in vivo feasibility, the measured responses of oxygenation and CCO responses to acute ischemia (e.g., blood pressure tests) in human participants are compared to data from the literature. Furthermore, we show that the new device’s measurements of oxygenated (HbO) and deoxygenated (HbR) hemoglobin in response to breath hold challenges are principled and consistent with previously reported findings. The validated SCISCCO system is finally applied to measure cerebral oxygenation and the redox state of CCO in participants during an attention test protocol. Twenty-five healthy adults completed an attention task that included nine 60-second periods of attention task, interleaved with 60-s periods of resting baseline. It has been well established that the frontal lobe of the human brain is active during tasks of attention. We therefore predicted that attention task should elicit an increase in HbO concentration accompanied by a decrease in redox state of CCO (e.g., ratio of oxidized CCO to reduced CCO) in frontal lobe brain regions as measured with the SCISCCO system. Our findings are consistent with our predictions: HbO concentration increases while CCO concentration decreases during the attention blocks relative to the resting baseline, thereby indicating an increase in oxidative metabolism of the frontal lobe brain regions of interest. Our systematic, multi-method approach thus validates the new device as well as the validity of the metabolic biomarkers that it measures. The SCISCCO system could be a new tool for monitoring brain and organ metabolism, which could be invaluable for screening concussion patients or use in an operating or emergency room to gauge patient’s organ response to treatments.