Noninvasive Measurement of Intervertebral Disc Mechanics with MR Elastography

描述（由申请人提供）：椎间盘退变的特征是纤维环（AF）、髓核（NP）和终板（EP）的组织和力学性能的渐进级联变化。在早期变性中，NP中的蛋白聚糖断裂导致含水量、渗透压和硬度降低。椎间盘退变的晚期特征是核从胶状物质转变为纤维状物质，房颤发生结构变化，随后房颤出现裂缝和撕裂。椎间盘退变的早期诊断对任何生物治疗策略的成功都至关重要。目前，临床MRI对椎间盘退变的诊断仅检测退变晚期的特征。新的基于核磁共振的技术，如钠成像、磁化转移、T1r和T2图，已被用于量化NP组成的早期变化。然而，在检测组织微观结构的变化时，组织力学性能比基于核磁共振的成分更敏感。尽管许多研究报道了早期椎间盘形成的力学意义，但椎间盘组织的力学特性尚未在体内测量。目前骨科组织的机械测试技术的破坏性是禁止在体内应用。因此，需要一种非侵入性、非破坏性的方法来测量椎间盘力学性能，作为退变的生物标志物。磁共振弹性成像是一种基于核磁共振的技术，用于测量软组织的弹性特性，已成功地用于诊断涉及机械特性变化的疾病。本研究的目的是应用磁共振弹性成像从完整的椎间盘节段测量椎间盘的弹性特性，并将这些特性与退变联系起来。具体来说，我们建议：目标1：采用MRE来测量椎间盘的弹性特性。1一个。修改我们的2D MRE设置以获得椎间盘弹性特性的三维（3D）测量。具体而言，通过在切片方向上添加相位编码梯度来修改二维MRI脉冲序列以获取三维数据；设计和构建一个梯度线圈，在高频下应用运动敏化梯度；修正了一种计算AF各向异性弹性特性的逆方法。1 b。整合所有这些组件，并通过比较MRE性能与传统组织力学扭转试验获得的结果来验证方法。目的2：测量和关联椎间盘和退变的力学特性。测量不同退变程度的完整椎间盘节段AF和NP的力学特性。将这些特性与使用Pfirrmann等级和连续尺度（如T1r和T2图）测量的退化相关联。这种相关性的结果将决定MRE在鉴别和诊断椎间盘退变早期阶段的敏感性。这项工作具有重要意义，因为它将提供一种急需的非侵入性方法来量化椎间盘的机械性能，以及未来应用MRE来测量椎间盘体内弹性性能所需的基础和技术发展。

DESCRIPTION (provided by applicant): Intervertebral disc degeneration is characterized by a progressive cascade of changes in organization and mechanical properties of annulus fibrosus (AF), nucleus pulposus (NP) and end plates (EP). In early degeneration, proteoglycan fragmentation in the NP leads to a decrease of water content, osmotic pressure and stiffness. Advanced stages of degeneration are characterized by a transition of the nucleus from a gelatinous material to a fibrous one, structural changes in the AF, followed by fissures and tears in the AF. Early diagnosis of disc degeneration is critical for the success of any biological treatment strategy. Currently, diagnosis of disc degeneration using clinical MRI only detects characteristics of advanced stages of degeneration. New MR-based techniques, such as sodium imaging, magnetization transfer, T1r and T2 maps, have been used to quantify early changes in NP composition. However, tissue mechanical properties are more sensitive than MR-based composition at detecting changes in the tissue microstructure. Despite the numerous studies reporting the mechanical implications of early disc generation, the mechanical properties of disc tissues haven't been measured in-vivo. The destructive nature of current mechanical testing techniques for orthopaedic tissues is prohibitive for in-vivo applications. Therefore, there is a need of non-invasive, non- destructive methods to measure disc mechanical properties to serve as a biomarker of degeneration. Magnetic Resonance Elastography is an MR-based technique to measure elastic properties of soft tissues that has been successfully used for the diagnosis of diseases that involve changes in the mechanical properties. The objective of this study is to apply Magnetic Resonance Elastography to measure elastic properties of the disc from intact disc segments and to correlate those properties with degeneration. Specifically, we propose to: Aim 1: Adapt MRE to measure elastic properties of in the intervertebral disc. 1A. Modify our 2D MRE set-up to obtain three-dimensional (3D) measurements of elastic properties of the intervertebral disc. Specifically, to modify the 2D MRI pulse sequence to acquire 3D data by adding a phase encoding gradient in the slice direction; design and build a gradient coil to apply a motion sensitizing gradient at high frequencies; modify an inverse method to calculate anisotropic AF elastic properties. 1B. Integrate all these components and validate the method by comparing MRE properties with those obtained by conventional tissue mechanical torsion tests. Aim 2: Measure and correlate mechanical properties of disc and degeneration. Measure mechanical properties of AF and NP of intact disc segments across a range of different degeneration levels. Correlate those properties with degeneration measured using the Pfirrmann grade and continuous scales such as T1r and T2 maps. Results from this correlation will determine the sensitivity of MRE to identify and diagnose early stages of degeneration in the disc. This work is significant in that it will provide a much-needed non-invasive method to quantify mechanical properties of the disc, as well as the basis and technical developments required for a future application of MRE to measure elastic properties of the disc in-vivo.