Precision blood pressure management after endovascular stroke therapy based on real-time autoregulation measurements

摘要 下面的K23提案是为耶鲁-纽约分校的神经危重护理和中风神经病学家尼尔斯·彼得森博士准备的 他是耶鲁大学医学院的助理教授。彼得森医生是一名内科医生- 具有人类脑血流动力学专业知识的科学家正在研究个性化的， 自动调节引导下的缺血性卒中后血压管理。约40%的缺血性心脏病患者 因颅内大血管闭塞(LVO)导致的中风表现为不能活动、卧床或死亡 尽管接受了血管内血栓切除术。急性期脑血管自动调节功能异常 LVO卒中时相增加相对脑低灌注或高灌注期继发性脑损伤的风险。 因此，自动调节引导的个性化血压管理是一种很有前途的替代方案 目前以固定阈值为目标的做法。通过为老年人提供更有利的生理环境 对于脑损伤，自我调节引导的方法可以减少继发性脑损伤，改善预后。 彼得森博士获得的初步数据已经证明了一项研究计划的可行性，该计划使用近 红外光谱和实时数据处理以识别特定于患者的血压范围 最佳的脑血流量。这项研究建议将评估外部的血压管理 个性化的自动调节限制增加了因脑梗塞进展或 出血性转化，导致不良结局发生率增加(目标1)。接下来，彼得森博士将 评价治疗性血压干预措施的有效性，并探讨 针对个性化血压范围的干预方案(目标2)。在博士的专家指导下。 凯文·谢斯，神经危重护理主任，伦道夫·马歇尔博士，哥伦比亚大学卒中科主任 和医学信息学主任辛西娅·勃兰特博士，这一K23奖项将允许彼得森博士 掌握信息学、高级信号处理和机器学习方面的技能，以增强当前 量化脑自动调节的方法，2)发展临床试验设计的专业知识，3)建立 致力于发现和临床评估基于生理学的个体化治疗的研究小组 中风后的战略，以及4)促进机构间合作和数据共享。这项提议将 利用耶鲁大学尖端的神经监测技术以及广泛的信息学和研究 来自耶鲁大学临床研究中心的资源，以产生对脑血流动力学的新见解 并确定治疗机会。在此颁奖期结束时，彼得森博士将处于有利地位 成为一名独立资助的研究人员，在大脑领域进行高质量的研究 血流动力学。他的长期目标是使用神经监测来开发基于生理的、个性化的、早期的 减少与中风相关的残疾和发病率的干预措施。

Abstract The following K23 proposal is for Dr. Nils Petersen, a Neurocritical Care and Stroke Neurologist at Yale-New Haven Hospital, and Assistant Professor at Yale University School of Medicine. Dr. Petersen is a physician- scientist with specialized knowledge of human cerebral hemodynamics who is investigating personalized, autoregulation-guided blood pressure management after ischemic stroke. About 40% of patients with ischemic stroke due to intracranial large-vessel occlusion (LVO) are rendered non-ambulatory, bedridden or deceased despite treatment with endovascular thrombectomy. Abnormalities in cerebrovascular autoregulation in the acute phase of LVO stroke increase the risk of secondary brain injury from relative cerebral hypo- or hyperperfusion. Thus, autoregulation-guided, personalized blood pressure management presents a promising alternative to the current practice of targeting fixed thresholds. By providing a more favorable physiologic environment for the injured brain, the autoregulation-guided approach may reduce secondary brain injury and improve outcomes. Preliminary data obtained by Dr. Petersen have demonstrated the feasibility of a research plan that uses near- infrared spectroscopy and real-time data processing to identify a patient-specific blood pressure range that yields optimal brain blood flow. This research proposal will evaluate if blood pressure management outside personalized limits of autoregulation increases the risk for neurologic worsening from infarct progression or hemorrhagic transformation, leading to increased rates of unfavorable outcome (Aim 1). Next, Dr. Petersen will evaluate the effectiveness of therapeutic blood pressure interventions and explore the feasibility of an intervention protocol targeting a personalized blood pressure range (Aim 2). Under the expert mentorship of Dr. Kevin Sheth, Chief of Neurocritical Care, Dr. Randolph Marshall, Director of Stroke Division at Columbia University, and Dr. Cynthia Brandt, Director of Medical Informatics, this K23 award will allow Dr. Petersen 1) to acquire skills in informatics, advanced signal processing and machine learning in order to enhance current methods of quantifying cerebral autoregulation, 2) to develop expertise in clinical trial design, 3) to build a research group dedicated to discovery and clinical evaluation of physiology-based individualized treatment strategies after stroke, and 4) to foster inter-institutional collaboration and data-sharing. This proposal will leverage Yale’s cutting-edge neuro-monitoring technologies along with extensive informatics and research resources from the Yale Center for Clinical Investigation to generate new insights into cerebral hemodynamics and identify treatment opportunities. At the conclusion of this award period, Dr. Petersen will be well-positioned to become an independently-funded investigator conducting high-quality research in the area of cerebral hemodynamics. His long-term goal is to use neuro-monitoring to develop physiology-based, personalized, early interventions to reduce the disability and morbidity associated with stroke.