A HEMODYNAMIC MODEL OF INTRACRANIAL PRESSURE DYNAMICS

颅内压紊乱，包括外伤性脑损伤和脑积水，可引起显著的发病率和死亡率。越来越多的证据表明，我们解释这些疾病病理生理学的许多“标准”理论应该重新考虑。在这个提议中，一个新的理论描述了高颅内压和脑积水的病理生理是使用生物工程建模方法和实验室实验研究相结合的研究。这个理论，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，依从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个传输在线电路，该电路可以模拟颅内压力变化与血流动力学改变的关系。为了提高模型的准确性，将从体外实验中估计各个电路参数。此外，还将使用急性脑积水的体内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与动物实验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、统一的颅内压病理生理理论，准确地代表和预测颅内压改变所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设提供了一种强有力的方法。改善对这些疾病的了解将为数百万受影响的患者提供新的和更好的治疗方式。

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.