Image-based modeling of nonlinear and anisotropic intervertebral disc mechanics

基于图像的非线性和各向异性椎间盘力学建模

• 批准号: 7825311
• 负责人: VICTOR H BAROCAS
• 金额: $ 50万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-21 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7825311
• 关键词: Address; Anisotropy; Area; Arts; Award; Biomedical Technology; Complex; Containment; Data; Delaware; Development; Devices; Drug Formulations; Economics; Elements; Failure; Fiber; Goals; Health; Hip region structure; Human; Image; In Situ; Injury; Intervertebral disc structure; Knee joint; Knowledge; Magnetic Resonance Imaging; Maps; Measurement; Measures; Mechanics; Medicine; Methods; Minnesota; Modeling; Morphologic artifacts; Musculoskeletal; Musculoskeletal System; New Jersey; Noise; Non-linear Models; Occupations; Operative Surgical Procedures; Patients; Pennsylvania; Performance; Physiologic pulse; Positioning Attribute; Property; Research; Research Personnel; Research Project Grants; Resolution; Shoulder; Signal Transduction; Site; Solid; Solutions; Stress; Structural Models; Structure; System; Technology; Testing; Time; Tissue Engineering; Tissue Sample; Tissues; Torsion; Training; Universities; Work; base; computer studies; economic impact; experience; graduate student; human tissue; image registration; implantation; improved; in vivo; innovation; insight; mechanical behavior; medical schools; member; next generation; nucleus pulposus; research study; response; technology development; tool

DESCRIPTION (provided by applicant): This application addresses the broad Challenge area (06) Enabling Technologies, and the specific Challenge Topic, 06-EB-109: Model-Driven Biomedical Technology Development. Structural models of musculoskeletal tissues to calculate internal stresses and strains are an essential technology to investigate mechanisms of injuries and failure. Moreover accurate models provide understanding to predict the consequence of surgical interventions, device implantation, and tissue engineering. This proposal addresses the challenge of modeling the intervertebral disc. For over three decades finite element models have proved valuable to study disc mechanics. However, the currently available disc models have three significant limitations that will be addressed in this proposal for improved fidelity to predict mechanical behavior. First, the measured annulus fibrosus (AF) properties that are input into models are based on excised tissue tests. Excising the tissue disrupts the fiber structure, which introduces artifacts into the material property measurement and does not represent the inhomogeneities that are reflected by the gradual alterations in disc composition and microarchitecture. Second, excising tissue samples eliminates the interfaces between the sub-structures. Third, current disc models use "cable" elements that are embedded within an isotropic solid element for the AF. Ostensibly this represents the AF structure; however, the AF composition and microarchitecture is complex, requiring a constitutive formulation that better reflects the AF anisotropy, nonlinearity, and inhomogeneity. The objective of this proposal is to develop an image-based disc model that incorporates the tissue's inhomogeneous, anisotropic, and nonlinear material properties. We will obtain a 3D structural model with spatially distributed material properties using sophisticated enabling technologies. Aim 1: Extend the established 2D MRI to high resolution 3D MRI of the disc under load. Evaluate the performance of the pulse sequence and adjust the sequence parameters as required to optimize resolution, contrast, and signal-to-noise ratio. Aim 2: Image human discs under multi-axial loading configurations including compression, bending, and torsion and calculate 3D strain maps using state-of-the-art diffeomorphic image registration. Aim 3: Apply inverse methods to the established constitutive formulation and the measured strain maps to determine material properties. Validate the model and material properties by predicting strain under loading configuration not used in property calculations. Repeat the computational study using different loading modes for parameter regression. At completion of this study, we will be able to accurately predict the stresses and strains within the disc due to the microstructural contribution of the fibrillar components and extrafibrillar matrix and in response to interactions between the disc substructures. Determining material properties in situ is an innovative solution to the current limitations of artifacts in excised tissue tests and the disruption of sub-structural interfaces. The significance of this work lies in the development of an invaluable tool for accurate modeling of disc mechanics, which is central to both understanding mechanical failure of the disc and treating it. This system will initially be applied to cadaveric human tissues; however, long term advances in imaging may permit extension to in vivo application and patient-specific modeling and analysis. Economic impact The proposed experiments described in this Challenge Proposal will create four full time positions between the sites at the University of Pennsylvania (2.5 postdoctoral researchers, 0.2 technicians) and University of Minnesota (1 graduate student, 0.5 postdoctoral researchers). The University of Pennsylvania School of Medicine is an internationally recognized leader in the creation of new knowledge and therapies to improve human health, and in the training of the next generation of scientific leaders. In pursuit of these goals, the UPenn School of Medicine extends its economic impact widely and deeply throughout Pennsylvania, New Jersey, and Delaware. Recent studies attributed 37,000 jobs and $5.4 billion in economic activity to Penn Medicine in 2008. As Minnesota's only research university, the University of Minnesota is the economic engine for the state. As such the University of Minnesota's impact is felt far and wide, with more than 21,500 jobs directly related to research grants awarded to the University. This application addresses the broad Challenge area (06) Enabling Technologies, and the specific Challenge Topic, 06-EB-109: Model-Driven Biomedical Technology Development. Structural models that calculate the disc internal stresses and strains are essential to investigate mechanisms of disc injuries, tears, and failure. Moreover accurate models will provide understanding to predict the consequence of surgical interventions, device implantation, and tissue engineering. Unfortunately, the currently available disc models lack the fidelity to predict mechanical behavior accurately. The objective of this proposal is to develop an image-based disc model that incorporates the tissue's inhomogeneous, anisotropic, and nonlinear material properties. The proposed experiments described in this Challenge Proposal will create four full time positions between the sites at the University of Pennsylvania (2.5 postdoctoral researchers, 0.2 technicians) and University of Minnesota (1 graduate student, 0.5 postdoctoral researchers).

描述（由申请人提供）：本申请解决了广泛的挑战领域 (06) 支持技术，以及具体的挑战主题 06-EB-109：模型驱动的生物医学技术开发。用于计算内部应力和应变的肌肉骨骼组织的结构模型是研究损伤和衰竭机制的重要技术。此外，准确的模型有助于预测手术干预、设备植入和组织工程的结果。该提案解决了椎间盘建模的挑战。三十多年来，有限元模型已被证明对于研究盘力学很有价值。然而，当前可用的椎间盘模型具有三个显着的局限性，本提案将解决这些局限性，以提高预测机械行为的保真度。首先，输入模型的测量纤维环 (AF) 特性基于切除的组织测试。切除组织会破坏纤维结构，这会在材料性能测量中引入伪影，并且不能代表椎间盘成分和微结构逐渐改变所反映的不均匀性。其次，切除组织样本消除了子结构之间的界面。第三，当前的圆盘模型使用嵌入在 AF 各向同性实体单元中的“电缆”单元。表面上这代表了 AF 结构；然而，AF 的组成和微结构很复杂，需要一种能够更好地反映 AF 各向异性、非线性和不均匀性的本构公式。该提案的目标是开发一种基于图像的椎间盘模型，该模型融合了组织的不均匀、各向异性和非线性材料特性。我们将使用先进的支持技术获得具有空间分布材料属性的 3D 结构模型。目标 1：将已建立的 2D MRI 扩展到负载下椎间盘的高分辨率 3D MRI。评估脉冲序列的性能并根据需要调整序列参数以优化分辨率、对比度和信噪比。目标 2：对多轴载荷配置（包括压缩、弯曲和扭转）下的人体椎间盘进行成像，并使用最先进的微分同胚图像配准计算 3D 应变图。目标 3：将反演方法应用于已建立的本构公式和测量的应变图，以确定材料特性。通过预测属性计算中未使用的负载配置下的应变来验证模型和材料属性。使用不同的加载模式进行参数回归重复计算研究。这项研究完成后，我们将能够准确预测椎间盘内由于纤维成分和纤维外基质的微观结构贡献以及椎间盘亚结构之间的相互作用而产生的应力和应变。原位确定材料特性是解决当前切除组织测试中伪影和亚结构界面破坏的局限性的创新解决方案。这项工作的意义在于开发了一种用于精确模拟椎间盘力学的宝贵工具，这对于理解椎间盘的机械故障和治疗它至关重要。该系统最初将应用于人体尸体组织；然而，成像技术的长期进步可能会扩展到体内应用和患者特异性建模和分析。经济影响 本挑战提案中描述的实验将在宾夕法尼亚大学（2.5 名博士后研究人员、0.2 名技术人员）和明尼苏达大学（1 名研究生、0.5 名博士后研究人员）的地点之间创建 4 个全职职位。宾夕法尼亚大学医学院在创造新知识和疗法以改善人类健康以及培训下一代科学领袖方面是国际公认的领导者。为了实现这些目标，宾夕法尼亚大学医学院将其经济影响广泛而深入地扩展到宾夕法尼亚州、新泽西州和特拉华州。最近的研究表明，2008 年宾大医学院创造了 37,000 个工作岗位和 54 亿美元的经济活动。作为明尼苏达州唯一的研究型大学，明尼苏达大学是该州的经济引擎。因此，明尼苏达大学的影响广泛而深远，有超过 21,500 个与授予该大学的研究资助直接相关的工作岗位。该应用程序解决了广泛的挑战领域 (06) 支持技术，以及特定的挑战主题 06-EB-109：模型驱动的生物医学技术开发。计算椎间盘内应力和应变的结构模型对于研究椎间盘损伤、撕裂和失效的机制至关重要。此外，准确的模型将有助于预测手术干预、设备植入和组织工程的结果。不幸的是，当前可用的椎间盘模型缺乏准确预测机械行为的保真度。该提案的目标是开发一种基于图像的椎间盘模型，该模型融合了组织的不均匀、各向异性和非线性材料特性。本挑战提案中描述的实验将在宾夕法尼亚大学（2.5 名博士后研究人员，0.2 名技术人员）和明尼苏达大学（1 名研究生，0.5 名博士后研究人员）之间创建 4 个全职职位。