A HEMODYNAMIC MODEL OF INTRACRANIAL PRESSURE DYNAMICS

颅内压紊乱，包括创伤性脑损伤和脑积水，可导致显著的发病率和死亡率。越来越多的证据表明，我们解释这些疾病的病理生理学的许多“标准”理论应该重新考虑。在该方案中，采用生物工程建模方法和实验室实验研究相结合的方法，研究了一种描述颅内压升高和脑积水的病理生理学的新理论。这一理论，我们称之为血流动力学理论，是基于颅内顺应性、脑血流阻抗和颅内压之间的相互关系。我们使用小动物模型进行的初步研究表明，顺应性和血流紊乱之间存在很强的相关性。该项目的总体目标是构建和验证一种传输线路电路，该线路能够模拟颅内压变化与血流动力学改变之间的关系。为了提高模型的准确性，单个电路参数将从体外实验中估计出来。此外，还将使用急性脑积水的活体模型来检验支持电路模型的理论基础。最后，将新电路模型的计算机模拟结果与动物实验得出的实际生理数据进行比较。该项目的长期目标是建立一个全面的、统一的颅内压病理生理学理论，准确地表示和预测受颅内压变化影响的各种临床疾病。生物工程建模技术的使用为通过模拟复杂的生理现象来检验假说提供了有力的方法。对这些疾病的更好理解将为数百万受影响的患者提供新的更好的治疗方式。

Disorders of intracranial pressure, including traumatic brain injury and hydrocephalus, can cause significant morbidity and mortality. There is increasing evidence that many of our "standard" theories explaining the pathophysiology of these disorders should be reconsidered. In this proposal, a novel theory describing the pathophysiology of elevated intracranial pressure and hydrocephalus is studied using a combination of bioengineering modeling methods and laboratory experimental investigations. The theory, which we termed the hemodynamic theory, is based on an interrelationship between intracranial compliance, cerebral blood flow impedance, and intracranial pressure. Our preliminary studies using a small animal model have demonstrated a strong correlation between compliance and disturbances in blood flow. The overall objective of this project is to construct and validate a transmission-line circuit that models intracranial pressure changes in relationship to altered hemodynamics. In order to enhance the accuracy of the model, the individual circuit parameters will be estimated from in vitro experiments. In addition, an in vivo model of acute hydrocephalus will be used to test the theoretical basis supporting the circuit model. Finally, the computer simulations of the new circuit model will be compared to the actual physiological data derived from the animal experiments. The long-term goal of this project is to establish a comprehensive, unifying theory of intracranial pressure pathophysiology that accurately represents and predicts the various clinical disorders affected by altered intracranial pressure. The use of bioengineering modeling techniques provides a powerful method to test hypotheses by simulating complex physiologic phenomenon. An improved understanding of these disorders will offer new and better treatment modalities for millions of affected patients.