Development and Early Clinical Evaluation of Noninvasive MRI Measurement of ICP

描述（由申请人提供）：这项生物工程-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）的新方法的临床应用。这些重要的神经生理参数是使用动态磁共振成像（MRI）测量血液和脑脊液（CSF）流入和流出大脑。这项新技术的可行性通过幻影、计算机模拟、非人类灵长类动物模型、健康志愿者和少量患者来证明。这些参数的无创量化对于改善几种神经问题的诊断和治疗具有潜在的重要意义。在本提案中，我们的目标是证明无创ICC测量的潜在临床应用，以研究相对常见但知之甚少的神经系统问题，Chiari畸形（CM）（与小脑扁桃体向下移位到椎管中有关）。一些证据表明ICC在这种疾病的病理生理中起重要作用。然而，由于这些患者的侵入性ICC测量与脑疝的风险增加有关，颅内依从性以前没有测量过。CM的无创ICC测量可能有助于解释病理生理学，并有可能改善这种衰弱性疾病的诊断和治疗。此外，由于MRI已经用于诊断CM，因此增加额外的扫描以获得无创的ICC测量是可行的。颅内顺应性量化的是颅内隔室在不增加压力的情况下适应容量增加（如脑肿胀）的能力，临床上应用更广泛的是ICP。我们基于mri的ICP测量依赖于ICC和ICP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和侵入性测量ICP之间的强线性相关性。在该方法被临床接受之前，提出的验证是必不可少的一步，并且可以在其他神经系统问题中评估无创MR-ICP的潜在高诊断价值。该提案的发展部分旨在改进核磁共振数据采集方案和缩短总体扫描时间，主要是为了通过对ICP进行多次采样来提高测量可靠性，并允许对ICP进行动态测量。拟议的发展工作还旨在通过标准化受试者的总脑组织体积和重量来改善脑总血流量（tCBF）的测量，tCBF是MR-ICP测量的副产品。初步结果表明，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.