Modeling and Assessment of Cerebrovascular Autoregulation

描述（由申请人提供）：头部损伤患者往往会出现继发性并发症，可能包括脑肿胀、脑循环受损和脑缺血。这项工作的目标是模拟脑血流的主动和被动调节的生物力学机制。该模型将为持续评估脑损伤患者脑血管自动调节的方法提供基础，从而改善重症监护管理和治疗。当自动调节功能完好时，脑血管床会随着脑灌注压（CPP）的升高和降低而收缩和扩张。当自动调节受损时，脑血管床内血管口径的变化被动地跟随CPP的变化。最近，我们已经应用系统识别建模技术的实验室和临床记录的ICP和动脉血压（ABP），以检查脑血管压力传输的最高模态频率（HMF）的变化。根据对这些压力记录的分析结果，提出了以下假设：当自动调节完整时，HMF的变化与脑灌注压（CPP）和动脉-小动脉床阻力的变化呈负相关。相反，当脑血管张力为被动时，HMF的变化与CPP和动脉-小动脉床阻力的变化直接相关。为了检验这一假设，将使用仔猪解决以下三个具体目标。使用配备有颅窗的小猪，我们将确定在动脉血气操纵诱导的完整和受损的压力调节期间，小动脉直径、通过激光多普勒和通过氢清除法测量的脑血流量、CPP和HMF的变化之间的关系。此外，我们将确定这些相同的关系引起的变化，不适当的血管舒张在人工升高ABP。使用颅内压动力学的三阶windkessel模型模拟ICP，将用于检查脑血流主动和被动调节的生物力学机制。

DESCRIPTION (provided by applicant): Patients with head-injury tend to develop secondary complications that may include brain swelling, impaired cerebral circulation, and cerebral ischemia. The goal of this work is to model the biomechanical mechanisms underlying active and passive regulation of cerebral blood flow. This model will provide the basis for a method to continuously assess cerebrovascular autoregulation of patients with brain injury, thereby permitting improved intensive care management and therapy. When autoregulation is intact, the cerebrovascular bed constricts and dilates in response to increases and decreases of cerebral perfusion pressure (CPP). When autoregulation is impaired, changes in the caliber of vessels within the cerebrovascular bed passively follow changes of CPP. Recently, we have applied system identification modeling techniques to laboratory and clinical recordings of ICP and arterial blood pressure (ABP) to examine changes in the highest modal frequency (HMF) of cerebrovascular pressure transmission. From findings based on an analysis of these pressure recordings, the following hypothesis has been developed: When autoregulation is intact, changes of the HMF are inversely related to changes of cerebral perfusion pressure (CPP) and resistance of the arterial-arteriolar bed. In contrast, when cerebrovascular tension is passive, changes of HMF are directly related to changes of CPP and resistance of the arterial-arteriolar bed. To test this hypothesis, the following three specific aims will be addressed using piglets. Using the piglet equipped with a cranial window, we will determine the relationships between changes of arteriolar diameter, cerebral blood flow measured by laser Doppler and by hydrogen clearance method, CPP, and the HMF during intact and impaired pressure regulation induced by manipulation of arterial blood gases. Furthermore, we will determine these same relationships for changes induced by inappropriate vasodilation during artificially elevated ABP. Simulation of ICP with a third order windkessel model of intracranial pressure dynamics will be used to examine the biomechanical mechanisms underlying active and passive regulation of cerebral blood flow.