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

摘要 以下K23建议是为耶鲁大学神经重症监护和中风神经学家Nils Petersen博士提出的 Haven医院，耶鲁大学医学院助理教授。彼得森医生是个内科医生- 具有人类大脑血液动力学专业知识的科学家， 缺血性卒中后自我调节指导的血压管理大约40%的缺血性患者 由于颅内大血管闭塞（LVO）引起的卒中导致卧床不起或死亡 尽管进行了血管内血栓切除术治疗。急性脑血管病患者脑血管自动调节功能异常 LVO期卒中增加了相对脑低灌注或高灌注引起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提供了一种有希望的替代方案， 目前的做法是以固定的门槛为目标。通过提供更有利的生理环境， 对于脑损伤患者，自动调节引导的方法可以减少继发性脑损伤并改善结果。 彼得森博士获得的初步数据证明了使用近- 红外光谱和实时数据处理来识别患者特定的血压范围， 最佳脑血流量这项研究计划将评估是否血压管理外 自动调节的个体化限制增加了梗死进展导致神经系统恶化的风险， 出血性转化，导致不良结局发生率增加（目的1）。接下来，彼得森博士将 评估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。 Kevin Sheth，神经重症监护主任，哥伦比亚大学卒中科主任兰多夫马歇尔博士 K23奖将使彼得森博士能够 掌握信息学，先进的信号处理和机器学习的技能，以提高当前的 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）建立一个 一个研究小组，致力于发现和临床评价基于生理学的个体化治疗 中风后的策略，和4）促进机构间的合作和数据共享。这项建议会 利用耶鲁大学的尖端神经监测技术，沿着广泛的信息学和研究 耶鲁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。在这个奖项期结束时，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利用神经监测来开发基于生理学的、个性化的、早期的 干预措施，以减少与中风相关的残疾和发病率。

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.