Multimodal Optical Imaging of Hyperdynamic Cerebral Responses to Cardiac Arrest and Resuscitation

项目摘要/摘要 该建议书概述了一项早期研究人员拨款(NIBIB开拓者R21)，以供PI开发光学 心脏骤停(CA)时大脑反应的实时成像技术。CA影响着超过55万人 在美国，80%-90%的幸存者由于脑血流动力学改变而患有严重的神经功能障碍。 临床上对定量工具的严重需求尚未得到满足，以监测脑血流灌注、新陈代谢和 CA、心肺复苏(CPR)和CPR后的神经血管偶联。 为了满足这一需求，我们将开发一个光学成像平台，并在CA和CPR的大鼠模型上进行验证 以产生新的临床翻译发现。这项技术将与量化相结合 我们独特的临床前重症监护环境中的脑电(QEEG)和生物标志物。我们的长期计划 目的是了解与神经学结果相关的脑血流动力学的时空变化， 制定干预措施，帮助CA患者。 我们的光学平台将提供实时、共同配准的多光谱空间频域成像 (SFDI)和激光散斑成像(LSI)的关键神经血管参数：氧合和脱氧血红蛋白，CBF， 组织散射和脑组织相对氧耗代谢率(RCMRO2)。我们将结合这一点 使用qEEG监测神经血管耦合和随后的神经结局参数。 该提案的具体目标集中在开发和验证该光学平台以进行调查 高度动态的大脑扰动，预测神经恢复，并允许实时干预。 目标1：开发并验证一种连续多模视频率光学成像平台 CA和CPR对脑神经血管反应的监测我们将建设视频率LSI和SFDI 测量组织中脉动血流、吸收和散射的仪器。我们将发展 在容易运动的时期(包括CPR)同时记录LSI和SFI的算法。我们将验证该平台 关于组织模拟模体和表征大脑变化剂量反应的活体大鼠模型 血流动力学和QEEG。 目标2：识别和调制CPR后40分钟从CA到&lt；的光学成像参数 预测神经功能恢复，并测试我们成像平台的治疗潜力。我们会 调节CBF和rCMRO2来改善神经活动，反之，我们将使用神经刺激来诱导 CA术中和心肺复苏后脑血流量和rCMRO2的变化 该提议将开发一种视频率光学平台，该平台具有独特的调查能力 CA和CPR高动力期的神经血管偶联及其改善后的潜力 CA的生存。我们计划利用这些资金开发具有竞争力的R01应用程序，用于翻译我们的 平台到神经重症监护病房，最终改善CA后的神经学结果。

PROJECT SUMMARY/ABSTRACT This proposal outlines an early stage investigator grant (NIBIB Trailblazer R21) for the PI to develop optical technologies for real-time imaging of cerebral response to cardiac arrest (CA). CA affects over 550,000 people in the U.S., and 80-90% of survivors suffer severe neurological deficits due to altered cerebral hemodynamics.. There is a severe unmet clinical need for quantitative tools to monitor cerebral perfusion, metabolism, and neurovascular coupling during CA, cardiopulmonary resuscitation (CPR), and post-CPR. To meet this need, we will develop an optical imaging platform and validate it in a rat model of CA and CPR to generate new clinically-translational discoveries. This technology will be combined with quantitative electroencephalography (qEEG) and biomarkers in our unique pre-clinical intensive care setting. Our long term goal is to understand spatiotemporal changes in brain hemodynamics related to neurological outcome, to develop interventions to help CA patients. Our optical platform will provide real-time, co-registered multispectral spatial frequency domain imaging (SFDI) and laser speckle imaging (LSI) of critical neurovascular parameters: oxy- and deoxyhemoglobin, CBF, tissue scattering, and relative cerebral metabolic rate of oxygen consumption (rCMRO2). We will combine this with qEEG to monitor neurovascular coupling and subsequent neurological outcome parameters. The specific aims of this proposal focus on developing and validating this optical platform to investigate hyperdynamic cerebral perturbations, predict neurological recovery, and allow for intervention in real-time. Aim 1: Develop and validate a multimodal video-rate optical imaging platform for continuous monitoring of cerebral neurovascular response to CA and CPR. We will build video-rate LSI and SFDI instrumentation to measure pulsatile blood flow, absorption, and scattering in tissue. We will develop algorithms to co-register LSI and SFI during motion-prone periods, including CPR. We will validate the platform on tissue-simulating phantoms and an in vivo rat model to characterize dose responses to changes in cerebral hemodynamics and qEEG. Aim 2: Identify and modulate optical imaging parameters from CA to <40 min post-CPR that are predictive of neurologic recovery and test therapeutic potential of our imaging platform. We will modulate CBF and rCMRO2 to improve neural activity, and conversely, we will use neuro-stimulation to induce changes in CBF and rCMRO2 during CA and after CPR. This proposal will develop a video-rate optical platform that is uniquely capable of investigating neurovascular coupling during hyperdynamic periods of CA and CPR, with potential to improve post- CA survival. We plan to utilize these funds to develop a competitive R01 application for translation of our platform to the neurointensive care unit to ultimately improve neurological outcome after CA.