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

项目总结 Chiari畸形1型(CM1)是一种以小脑结构缺陷为特征的病理改变。 相关症状可包括反复头痛、肌肉无力、睡眠障碍，以及 最极端的情况，甚至瘫痪。到目前为止，诊断是基于对患者的评估 神经病史结合核磁共振或CT检查。然而，缺乏统一和明确的 患者的症状如此明显，估计有320万受影响的患者没有 表现出足以导致诊断的严重症状。因此，提高诊断准确率将是 鉴于Chiari畸形的早期诊断和随后的手术治疗可能导致 以极大地改善临床结果。一个被忽视的因素，被认为是 诊断Chiari畸形等阻塞性脑疾病的方法是脑部运动。当心脏收缩时 在心动周期中松弛，动脉血压的周期性变化沿着 血管系统，导致大脑相对局部的运动和变形，这是非常微妙和 在传统的电影MRI图像上很难看到和量化。然而，这样的动议预计会随之而来。 阻塞性脑畸形患者的不同时空模式。我们有 最近开发了一种名为放大磁共振成像(AMRI)的新方法，它使用了 视频放大算法，放大心脏门控脑MRI扫描中的细微空间差异。这 入路显示脑实质变形，动脉和脑脊液移位由心脏引起。 搏动性。我们假设CM1患者的解剖结构导致小脑、脊髓和 无法用标准成像方法可靠地捕捉到的桥脑运动，但可以用我们的 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 跟踪心脏周期中的3D大脑运动。我们将首先通过计算验证3D-AMRI方法 幻影模型，由具有不同属性的可变形固体组成。同时，我们将测试3D-AMRI 方法在健康成人人群中，获得特定年龄和性别的正常脑活动范围 大脑的不同区域。最后，AMRI的潜在诊断价值将在CM1患者中进行测试， 我们将在那里将来自AMRI的CM1脑运动数据与健康志愿者的数据进行比较。阿姆里有 广泛临床应用的潜力和重大影响，因为它可以放大和表征小的，通常 几乎感觉不到运动，可以可视化组织的生物力学反应，使用心跳作为一种 内生机械驱动。这种方法的进一步发展可以使早期诊断和 CM1以外的脑病理干预，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；可能会消除不必要的侵入性脑部手术； 并可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.