A HEMODYNAMIC MODEL OF INTRACRANIAL PRESSURE DYNAMICS

颅内压障碍，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，我们许多解释这些疾病的病理生理学的“标准”理论应该重新考虑。 在这个建议中，一个新的理论描述颅内压升高和脑积水的病理生理学研究使用生物工程建模方法和实验室实验研究相结合。 该理论，我们称之为血液动力学理论，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的初步研究已经证明了顺应性和血流紊乱之间的强相关性。本项目的总体目标是构建和验证传输线回路，该传输线回路模拟颅内压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，将使用急性脑积水的体内模型来测试支持电路模型的理论基础。最后，新电路模型的计算机模拟将与来自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的，统一的颅内压病理生理学理论，准确地代表和预测颅内压改变影响的各种临床疾病。 生物工程建模技术的使用提供了一种通过模拟复杂生理现象来检验假设的有力方法。 对这些疾病的进一步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.