Amplified MRI (aMRI): A novel way to investigate the pathophysiology ofChiari Malformation

项目摘要 基亚里畸形1型（CM 1）是一种以小脑结构缺陷为特征的病理学， 相关的神经病学，可能包括复发性头痛，肌肉无力，睡眠障碍， 最极端的情况甚至瘫痪到目前为止，诊断是基于对病人的评估， 神经系统病史结合MRI或CT检查。然而，缺乏统一和明确的 患者中的寄生虫病是如此明显，估计有320万受影响的患者没有 显示出足以导致诊断的症状。因此，提高诊断准确性将是 至关重要的是，考虑到基亚里畸形的早期诊断和随后的手术治疗可能导致 临床结果的显著改善。一个被忽视的元素，被认为是一个主要的候选人， 诊断诸如基亚里畸形的阻塞性脑疾病是脑运动。当心脏收缩时， 由于在心动周期中的舒张，动脉血压的周期性变化沿着 血管，导致大脑的相对局部化的运动和变形，这是非常微妙的， 难以在传统电影MRI图像上看到和量化。然而，预计这些动议将随后提出， 不同的空间和时间模式的患者患有梗阻性脑畸形。我们有 最近开发了一种称为放大磁共振成像（aMRI）的新方法，该方法使用 视频放大算法，以放大心脏门控脑MRI扫描中的细微空间变化。这 这种方法揭示了脑实质的变形，以及由于心脏病引起的动脉和CSF的移位。 搏动性我们假设CM 1患者的解剖结构导致小脑、脊髓和 标准成像方法不能可靠地捕获脑桥运动，但可以通过我们的 aMRI技术。为了验证这一假设，我们建议将我们的aMRI方法扩展到捕获和定量 跟踪心动周期中的3D大脑运动。我们将首先验证3D-aMRI方法与计算 体模模型，由不同属性的可变形实体组成。同时，我们将测试3D-aMRI 方法在健康成年人群中进行，并获得年龄和性别特异性的正常脑运动范围， 大脑的不同区域。最后，aMRI的潜在诊断价值将在CM 1患者中进行测试， 我们将比较aMRI导出的CM 1脑运动数据与健康志愿者的脑运动数据。aMRI具有 由于它可以放大和表征小的，通常 几乎察觉不到的运动，并可以可视化组织的生物力学反应，使用心跳作为 内源性机械驱动这种方法的进一步发展可以实现早期诊断， 干预除CM 1以外的脑病理，如创伤性脑损伤、脑积水、阿尔茨海默病 疾病和其他神经退行性疾病;可能消除不必要的侵入性脑手术的需要; 并且可以提供一种可靠的方法来监测治疗干预后的进展。

PROJECT SUMMARY Chiari Malformation type 1 (CM1) is a pathology characterized by structural defects in the cerebellum and a vast associated symptomatology which can include recurrent headaches, muscle weakness, sleep disorders and, in the most extreme cases, even paralysis. So far, diagnosis is based on an assessment of the patient's neurological history combined with an MRI or CT examination. However, the lack of a uniform and clear symptomatology among patients is so pronounced that an estimated 3.2 million of the patients affected do not show symptoms significant enough to lead to a diagnosis. Increasing diagnostic accuracy would therefore be of crucial importance, given that early diagnosis of Chiari malformation and subsequent surgical treatment can lead to highly improved clinical outcomes. One overlooked element that is thought of as a prime candidate for diagnosing obstructive brain disorders such as Chiari Malformation is brain motion. As the heart contracts and relaxes during the cardiac cycle, periodic variations in arterial blood pressure are transmitted along the vasculature, resulting in relatively localized motions and deformations of the brain, which are very subtle and difficult to see and quantify on traditional cine MRI images. Such motions, however, are expected to follow different spatial and temporal patterns in patients suffering from obstructive brain malformations. We have recently developed a novel method called amplified Magnetic Resonance Imaging (aMRI), which uses a video magnification algorithm to amplify the subtle spatial variations in cardiac-gated brain MRI scans. This approach reveals deformations of the brain parenchyma, and displacements of arteries and CSF due to cardiac pulsatility. We hypothesize that the anatomy of CM1 patients causes an increased cerebellar, spinal cord, and pons motion which cannot be reliably captured with standard imaging methods but can be assessed with our aMRI technique. To test this hypothesis, we propose to extend our aMRI method to to capture and quantitatively track 3D brain motion during the cardiac cycle. We will first validate the 3D-aMRI method with computational phantom models, consisting of deformable solids of varying properties. In parallel, we will test the 3D-aMRI method in a healthy adult population and obtain age and gender specific normal ranges of brain motion in different regions of the brain. Finally, the potential diagnostic value of aMRI will be tested in patients with CM1, where we will compare the aMRI-derived CM1 brain motion data against those of healthy volunteers. aMRI has the potential for widespread clinical use and significant impact since it can amplify and characterize small, often barely perceptible motion and can visualize the biomechanical response of tissues using the heartbeat as an endogenous mechanical driver. Further development of this method could enable earlier diagnosis and intervention of brain pathologies other than CM1 such as traumatic brain injury, hydrocephalus, Alzheimer's disease, and other neurodegenerative diseases; may remove the need for unnecessary invasive brain surgery; and may provide a reliable method to monitor progress following therapeutic intervention.