Non-invasive monitoring of brain health during cardio-pulmonary bypass

项目总结 尽管不断改善，但涉及体外循环(CPB)的主要血管和心脏手术仍然取得了成果 神经损伤率很高。CPB期间的病理生理变化导致药代动力学改变 使麻醉管理复杂化，并显著改变主要器官的血流。麻醉剂和镇痛剂都有 药物以中枢神经系统为靶点，与潜在的大脑自动调节受损一起，可能导致 向大脑输送的氧气不足。而对患者的全身血流动力学和呼吸监测 虽然已经使用了很长时间，但目前还没有一个公认的评估大脑健康的标准。一些脑血氧仪，基于 关于连续波近红外光谱测量，市场上已有。然而，尽管研究表明一些 手术中脑部血氧饱和度(SO2)下降的效用与神经学相关 但是，这些标准并没有被采纳为临床标准。这在很大程度上是因为它们基于廉价的技术 以及需要许多假设的方法，使它们对脑外污染敏感，无法 为指导临床干预提供量化门槛。此外，仅对二氧化硫的解释是模棱两可的，因为它 反映了多种全身和脑生理参数以及临床情况的综合影响，包括 脑血流量、氧耗量、红细胞压积和体温。 在此应用中，我们建议开发一种最先进的非侵入性脑健康监测工具，以提供实时 对大脑功能状态的多方面反馈。利用我们集团在 仪器的发展，我们将结合频域近红外光谱以及漫反射相关 用本征或超声辅助估计组织层厚度的多距离光谱测量 通过以下方法获得血流灌注、血红蛋白氧合和脑氧代谢的定量测量 创新的基于蒙特卡罗的光传输建模算法。我们将确定我们的准确性和精密度 使用组织真实感模型和微型猪动物模型进行测量。接下来，我们将执行验证 健康受试者在常氧、高氧和高碳酸血症状态下的脑电监测 使用MRI方法进行灌注和区域静脉氧合。最后，我们将进行一项试点临床测量 在体外循环下接受心血管手术的患者。我们假设大脑中的 术中氧合和血流灌注可预测神经损伤、新的缺血性病变的发展 弥散加权磁共振成像和延长住院时间，优于目前的脑氧仪。我们将演示 在手术室使用我们的设备监测脑健康的可行性和收集的数据将作为依据 用于进一步的假设生成和计划后续的、有针对性的临床研究。我们希望在以下方面取得重大进展 最先进的非侵入性神经监测工具，并使个性化护理达到新的水平，可以导致 减少体外循环下外科手术的负面结果。

PROJECT SUMMARY Despite continued improvements, major vascular and cardiac surgeries involving cardio-pulmonary bypass (CPB) still result in high rates of neurological injury. Pathophysiologic changes during CPB result in pharmacokinetic alterations that complicate the management of anesthesia and significantly alter major organ blood flow. Both anesthetic and analgesic agents target the central nervous system and, in conjunction with potentially impaired cerebral auto-regulation, can result in insufficient delivery of oxygen to the brain. While systemic hemodynamic and respiratory monitoring of the patients has been used for a long time, there is no accepted standard for assessing brain health. A number of cerebral oximeters, based on continuous-wave near-infrared spectroscopy measurements exist on the market. However, despite studies showing some utility in that drops in brain hemoglobin oxygen saturation (SO2) during surgery have been correlated with neurological deficits, they have not been adopted as clinical standards. This is largely because they are based on inexpensive technology and approaches that require many assumptions, making them sensitive to extracerebral contamination and unable to provide a quantitative threshold for guiding clinical interventions. Further, interpretation of SO2 alone is ambiguous, as it reflects the combined influence of multiple systemic and cerebral physiological parameters and clinical conditions, including cerebral blood flow, oxygen consumption, hematocrit, and temperature. In this application, we propose to develop a state-of-the art non-invasive brain health monitoring tool to provide real-time feedback on multiple aspects of the brain functional status. Leveraging the substantial experience of our group in instrumentation development, we will combine frequency domain near-infrared spectroscopy as well as diffuse correlation spectroscopy measurements at multiple distances with intrinsic or ultrasound assisted estimates of tissue layer thicknesses to obtain quantitative measures of perfusion, hemoglobin oxygenation and cerebral oxygen metabolism by means of innovative Monte Carlo based light transport modeling algorithms. We will determine the accuracy and precision of our measurements using both tissue-realistic phantoms and a miniature pig animal model. Next, we will perform validation measurements in healthy human subjects during normoxic, hyperoxic and hypercapnic states while monitoring brain perfusion and regional venous oxygenation using MRI methods. Finally, we will perform a pilot clinical measurements in patients undergoing cardiovascular surgery under cardio-pulmonary bypass. We hypothesize that decreases in brain oxygenation and perfusion during surgery are predictive of neurological injury, development of new ischemic lesions on diffusion weighted MRI and extended hospital stay and superior to current cerebral oximeters. We will demonstrate the feasibility of monitoring cerebral health using our device in the operating room and the collected data will serve as a basis for further hypothesis generation and to plan follow-up, targeted clinical studies. We hope to offer a significant advance in the state-of-the art of non-invasive neuromonitoring tools, and enable a new level of personalized care that can lead to a reduction in negative outcomes resulting from surgical procedures under cardio-pulmonary bypass.