Dynamical Assessment of Cerebral Autoregulation

描述（由申请人提供）：脑自动调节功能在卒中和创伤性脑损伤（TBI）后丧失，该功能可维持灌注以响应全身血压（BP）的波动。迫切需要无创性床边方法来识别自动调节受损的人，这些人可能会增加中风和不良后果的风险。第一阶段的目标是：1）建立和优化多模式压力流（MMPF）方法，这是一种利用经颅多普勒超声定量测量非平稳血压（BP）和脑血流速度（BFV）波动的脑自动调节的新方法。主要的突破是，MMPF现在允许测量瞬时BP和BFV相位关系在较长的时间段从自发波动在静息条件下。我们将应用MMPF方法评估动态自动调节，在仰卧休息条件下，并在Valsalva动作和坐立测试期间使用瞬时BP-BFV相位关系。MMPF分析将复杂的BP和BFV信号分解为经验模式，表示其瞬时频率-幅度调制。瞬时BP-BFV相位关系将被用作动态自动调节的度量。2)为了验证使用BP-BFV对这些生理动作的反应从MMPF获得的自动调节测量值，并将其与在118名健康受试者、75名高血压受试者、30名糖尿病受试者和50名中风受试者的人群中获得的标准自动调节指数进行比较。3)在30例创伤性脑损伤患者中，使用来自Beth Israel Deaconess Medical Center的晕厥和福尔斯实验室（SAFE）和剑桥大学的现有数据库，通过动脉内压（ABP）、颅内压（ICP）和脑灌注压（CPP=ABP-ICP）以及BFV的有创测量来验证MMPF测量。脑自动调节的评估在临床和研究医学的许多领域中是至关重要的。因此，在第二阶段，我们计划将MMPF软件纳入现有的经颅多普勒系统，以提供一个新的，广泛适用的，实用的工具，在临床环境中评价脑自动调节。该项目开发的分析技术可能有助于早期发现中风高危受试者。从这项创新技术中获得的定量测量也可以作为监测中风后患者的指标。因此，该项目可能会产生重大的社会经济影响。

DESCRIPTION (provided by applicant): Cerebral autoregulation that maintains perfusion in response to fluctuations of systemic blood pressure (BP) is lost post-stroke and traumatic brain injury (TBI). Noninvasive bedside methods are urgently needed to identify people with impaired autoregulation who may be at increased risk for stroke and adverse outcomes. The phase I goals are: 1) To develop and optimize the multimodal pressure flow (MMPF) method, a new approach to quantify cerebral autoregulation from nonstationary blood pressure (BP) and cerebral blood flow velocity (BFV) fluctuations using transcranial Doppler ultrasound. The major breakthrough is that the MMPF now allows measurement of instantaneous BP and BFV phase relationships over longer time period from spontaneous fluctuations under resting conditions. We will apply the MMPF method to the assessment of dynamic autoregulation using the instantaneous BP-BFV phase relationships during supine resting condition, and during the Valsalva maneuver and the sit-to-stand test. The MMPF analysis decomposes complex BP and BFV signals into empirical modes, representing their instantaneous frequency-amplitude modulation. Instantaneous BP-BFV phase relationships will be used as a measure of dynamical autoregulation. 2) To validate autoregulation measurements derived from the MMPF using BP-BFV responses to these physiological maneuvers, and to compare them to standard autoregulation indices obtained in populations of 118 healthy, 75 hypertensive, 30 diabetic and 50 stroke subjects. 3) To validate MMPF measurements using invasive measurements of intraarterial pressure (ABP), intracranial (ICP) and cerebral perfusion pressure (CPP=ABP-ICP) and BFV in 30 patients with traumatic brain injury, using existing databases from the Syncope and Falls laboratory (SAFE) at the Beth Israel Deaconess Medical Center and from the University of Cambridge. The assessment of cerebral autoregulation is of vital importance in many areas of clinical and investigative medicine. Therefore, in Phase II we plan to incorporate the MMPF software into existing transcranial Doppler systems in order to provide a new, widely applicable, practical tool for evaluation of cerebral autoregulation in clinical settings. The analysis technique developed by this project may help early detection of subjects at high risk of stroke. The quantitative measurements derived from this innovative technology can also serve as indices for monitoring post-stroke patients. Therefore, this project may have substantial socioeconomic impact.