Noninvasive Measurement of Intervertebral Disc Mechanics with MR Elastography

描述(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)的组织和力学特性的进行性级联变化。在变性的早期，NP中的蛋白多糖断裂导致水分含量、渗透压和硬度的下降。晚期退变的特征是细胞核从胶状物质转变为纤维状物质，房颤结构改变，随后房颤出现裂缝和撕裂。椎间盘退变的早期诊断对于任何生物治疗策略的成功都至关重要。目前，使用临床MRI诊断腰椎间盘退变只能检测到退变晚期的特征。基于磁共振的新技术，如钠成像、磁化转移、T1和T2图，已被用于量化NP组成的早期变化。然而，在检测组织微结构的变化时，组织机械特性比基于MR的组合物更敏感。尽管许多研究报道了早期椎间盘形成的力学意义，但还没有在体内测量过椎间盘组织的力学特性。目前骨科组织的机械测试技术的破坏性对于体内应用是令人望而却步的。因此，需要非侵入性、非破坏性的方法来测量椎间盘的机械性能，以作为退变的生物标记物。磁共振弹性成像是一种基于磁共振的测量软组织弹性特性的技术，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技术从完整的节段测量椎间盘的弹性特性，并将这些特性与退变相关联。具体地说，我们建议：目标1：使MRE用于测量椎间盘中的弹性特性。1A.修改我们的2D MRE设置，以获得对椎间盘弹性特性的三维(3D)测量。具体地说，通过在切片方向添加相位编码梯度来修改2D MRI脉冲序列以获取3D数据；设计并构建梯度线圈以在高频应用运动敏化梯度；修改逆方法以计算各向异性AF弹性特性。1B.集成所有这些组件，并通过将MRE特性与传统组织机械扭转测试获得的特性进行比较来验证该方法。目的2：测量和关联退变和退变的力学性能。测量一系列不同退变程度的完整节段的AF和NP的机械性能。将这些特性与使用Pfirmann等级和连续标度(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在识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，以及为将来应用MRE测量体内椎间盘的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.