NONINVASIVE MEASUREMENT OF INTRACRANIAL PRESSURE

颅内压升高仍然是神经系统疾病患者治疗中的一个关键问题，也是这些患者最常见的死亡原因。如果早期发现颅内压升高，是可以处理和治疗的。因此，测量颅内压对诊断和治疗决策具有重要意义。目前，只有有创技术可用于测量绝对颅内压。这些技术需要对中枢神经系统(CNS)进行物理渗透。本项目的目标是开发无创测量颅内压的技术。无创性测量颅内压将以较低的成本进行，并且对患者没有风险和痛苦。因此，这一重要的临床参数将被更频繁地测量，并可能显著改善有神经问题的患者的诊断和治疗决策。该项目综合了人类神经生理学、流体力学原理和动态磁共振成像技术的知识，开发了一种新的非侵入性测量颅内压的方法。这项技术是新颖的，因为它利用了每个心动周期中自然发生的颅内体积(ICV)和颅内压的变化，而不是通过外部干预改变中枢神经系统的状态。由于颅内压和体积变化的比率是颅内压的已知函数，因此对这些变化的比率的测量提供了一种衡量颅内压的方法。心动周期内的颅内压和ICV的变化将通过脑脊液(CSF)和血液容量流率的MRI测量来计算。ICV的变化将从进入颅骨的血和脑脊液的净体积流量中获得。根据脑脊液脉动压力梯度估计颅内压的变化。脑脊液压力梯度将通过动态测量颈椎的MRI脑脊液流量来计算。在对狒狒的初步研究中，颅内压的变化(即峰峰脉动的脑脊液压力梯度)与脉动脑脊液压力梯度的峰峰之间呈线性相关。该项目的目的是论证拟议技术的可行性。具体目标是：1.优化MRI方案和数据分析，以确保ICV变化和压力梯度测量的重复性和准确性。2.使用动物模型和计算流体动力学模拟来评估根据脑脊液压力梯度测量所估计的颅内压变化的准确性。3.在正常和升高的颅内压动物模型上，通过与有创测量的比较，评价无创技术的准确性。

Elevated intracranial pressure (ICP) remains a critical problem in management of patients with neurological problems and is the most common cause of death in these patients. Elevated ICP can be managed and treated if detected at an early stage. Therefore, measurement of ICP is important for diagnosis and treatment decisions. At present, only invasive techniques are available for measurement of absolute ICP. These techniques require physical penetration of the central nervous system (CNS). The objective of this project is to develop the technology for non-invasive measurement of ICP. The non-invasive measurement of ICP would be at a lower cost and without risk or pain to the patient. Hence, this important clinical parameter would be measured more often and may significantly improve the diagnosis and treatment decisions for patients with neurological problems. The proposed project integrates knowledge from human neuro-physiology, principles of fluid dynamics, and dynamic MRI techniques in developing a novel method to non-invasively measure ICP. The technique is novel as it makes use of the change in intracranial volume (ICV) and ICP that occur naturally during each cardiac cycle rather than altering the state of the CNS by external intervention. Since the ratio of intracranial pressure and volume changes is a known function of ICP, a measurement of the ratio of these changes provides a measure of ICP. The changes in ICP and ICV during the cardiac cycle will be computed from MRI measurements of cerebrospinal fluid (CSF) and blood volumetric flow rates. The ICV change will be obtained from the net volumetric flow of blood and CSF into the cranium. The ICP changes will be estimated from pulsatile CSF pressure gradient. The CSF pressure gradient will be computed from dynamic MRI CSF flow measurement in the cervical spine. In preliminary work on a baboon, the change in ICP (i.e., the peak-to-peak pulsatile ICP) was linearly correlated with the peak-to-peak of the pulsatile CSF pressure gradient. The objective of this project is to demonstrate the feasibility of the proposed technology. The specific aims are: 1. Optimize the MRI protocol and data analysis for reproducibility and accuracy of ICV change and pressure gradient measurements. 2. Evaluate the accuracy of the estimated ICP changes from CSF pressure gradient measurements using animal model and computational fluid dynamic simulations. 3. Evaluate accuracy of the non-invasive technique by comparison with invasive measurements on an animal model of normal and elevated ICP.