Development and Early Clinical Evaluation of Noninvasive MRI Measurement of ICP

描述(申请人提供)：生物工程-放射学-神经外科合作旨在进一步开发和测试一种无创测量颅内顺应性(ICC)和颅内压(ICP)的新方法的临床实用性。这些重要的神经生理参数是使用血液和脑脊液(CSF)进出大脑的动态磁共振成像(MRI)来测量的。这项新技术的可行性通过使用幻影、计算机模拟、非人灵长类动物模型、健康志愿者和少量患者进行了论证。这些参数的非侵入性量化对于改善几个神经学问题的诊断和治疗具有潜在的重要意义。在这项建议中，我们旨在展示无创ICC测量的潜在临床应用，以研究一种相对常见且知之甚少的神经学问题-Chiari畸形(CM)(与小脑扁桃体向下移位进入椎管有关)。一些证据表明ICC在本病的病理生理学中起着重要作用。然而，由于这些患者中与侵入性ICC测量相关的脑突出风险增加，以前没有测量过颅内顺应性。CM的无创性ICC测量可能有助于解释其病理生理学机制，并有可能改善这种衰弱疾病的诊断和治疗。此外，由于MRI已经被用于诊断CM，因此增加额外的扫描以非侵入性地获得ICC测量将是可行的。虽然颅内顺应性量化了颅内隔室在不大幅增加压力的情况下适应容量增加(例如，脑肿胀)的能力，但临床上更广泛地使用的是颅内压。我们基于MRI的颅内压测量依赖于ICC和颅内压之间的反向关系。我们建议进一步验证我们在9例患者中发现的MR-ICP和侵袭性测量的颅内压之间的强线性相关性。在该方法可以在临床上被接受之前，建议的验证是必不可少的一步，并且非侵入性MR-ICP的潜在高诊断价值可以在其他神经学问题中得到评估。该提案的发展部分旨在改进磁共振成像数据采集计划和缩短总体扫描时间，主要是通过对颅内压进行多次采样来提高测量可靠性，并允许对颅内压进行动态测量。拟议的开发工作还旨在通过归一化受试者的总脑组织体积和重量来改进总脑血流量(TCBF)的测量，tCBF是MR-ICP测量的副产品。初步结果显示，标准化tCBF测量的个体间变异性较小。

DESCRIPTION (provided by applicant): This bioengineering-radiology-neurosurgery partnership aims to further develop and test the clinical utility of a novel method for non-invasive measurement of intracranial compliance (ICC) and intracranial pressure (ICP). These important neurophysiologic parameters are measured using dynamic magnetic resonance imaging (MRI) of blood and cerebrospinal fluid (CSF) flows to and from the brain. The feasibility of this new technique is demonstrated using phantoms, computer simulations, non-human primate animal model, healthy volunteers, and small number of patients. Noninvasive quantification of these parameters is potentially important for improved diagnosis and treatment of several neurological problems. In this proposal we aim to demonstrate the potential clinical utility of a noninvasive ICC measurement to study a relatively common and poorly understood neurological problem, Chiari Malformations (CM) (associated with downward displacement of the cerebellar tonsils into the spinal canal). Some evidence suggests that ICC plays an important role in the pathophysiology of this disorder. However, because of increased risk of brain herniation associated with invasive ICC measurements in these patients, intracranial compliance has not been measured previously. Noninvasive ICC measurement in CM may help explain the pathophysiology and will potentially improve the diagnosis and treatment of this debilitating disorder. Moreover, since MRI is already used to diagnose CM, it would be practical to add the additional scan to obtain the ICC measurement noninvasively. While intracranial compliance quantifies the ability of the intracranial compartment to accommodate increase in volume (e.g., brain swelling) without a large increase in pressure, it is ICP that is more widely used clinically. Our MRI-based measurement of ICP relies on the inverse relationship between ICC and ICP. We propose further validations of a strong linear correlation we found between MR-ICP and invasively measured ICP in 9 patients. The proposed validations are an essential step before the method can become clinically acceptable and the potentially high diagnostic value of a noninvasive MR-ICP can be assessed in other neurological problems. The developmental components of the proposal aim at improving the MRI data acquisition scheme and at shortening overall scan time, primarily for increased measurement reliability by multiple sampling of ICP and for allowing dynamic measurements of ICP. The proposed developmental work also aims to improve measurements of total cerebral blood flow (tCBF), a byproduct of the MR-ICP measurement, by normalizing for the subject's total brain tissues volumes and weights. Preliminary results demonstrated lesser inter-individual variability of the normalized tCBF measurement.