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: 7937050
• 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 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7937050
• 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）：本申请涉及广泛的挑战领域（06）使能技术，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。肌肉骨骼组织的结构模型，以计算内部应力和应变是一个必要的技术，研究损伤和失败的机制。此外，准确的模型提供了理解，以预测手术干预，器械植入和组织工程的后果。该提案解决了椎间盘建模的挑战。三十多年来，有限元模型被证明是研究椎间盘力学的有价值的模型。然而，目前可用的椎间盘模型有三个显著的局限性，这将在本提案中得到解决，以提高预测机械性能的保真度。首先，输入到模型中的测量的纤维环（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，并且不代表椎间盘组成和微结构逐渐变化所反映的不均匀性。其次，切除组织样本消除了子结构之间的界面。第三，目前的光盘模型使用“电缆”的元素，嵌入在一个各向同性的固体元素的AF。表面上，这代表AF结构，但是，AF的组成和微架构是复杂的，需要一个本构制剂，更好地反映AF的各向异性，非线性和不均匀性。本建议的目的是开发一个基于图像的光盘模型，结合组织的不均匀，各向异性和非线性材料特性。我们将使用先进的使能技术获得具有空间分布材料特性的3D结构模型。目的1：将已建立的2D MRI扩展到高分辨率的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。目标二：在包括压缩、弯曲和扭转在内的多轴载荷配置下对人类椎间盘进行成像，并使用最先进的几何形态图像配准计算3D应变图。目的3：将逆方法应用于建立的本构关系和测量的应变图，以确定材料特性。通过预测未用于性能计算的加载配置下的应变来验证模型和材料性能。使用不同的加载模式重复计算研究以进行参数回归。在这项研究完成后，我们将能够准确地预测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，椎间盘内的应力和应变。原位确定材料特性是一种创新的解决方案，可以解决目前切除组织测试中的伪影和子结构界面破坏的局限性。这项工作的意义在于一个宝贵的工具，用于精确的椎间盘力学模型的发展，这是核心的理解机械故障的光盘和治疗it. This系统最初将被应用于尸体人体组织，但是，长期的成像技术的进步可能会允许扩展到体内应用和患者特定的建模和分析。经济影响本挑战提案中描述的拟议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）之间创建四个全职职位。宾夕法尼亚大学医学院是国际公认的领导者，致力于创造新知识和疗法以改善人类健康，并培养下一代科学领导者。为了实现这些目标，宾夕法尼亚大学医学院在整个宾夕法尼亚州，新泽西和特拉华州广泛而深入地扩大其经济影响。最近的研究将2008年的37,000个工作岗位和54亿美元的经济活动归功于宾夕法尼亚大学医学院。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是深远而广泛的，有超过21，500个工作岗位直接与授予大学的研究赠款有关。该应用程序解决了广泛的挑战领域（06）使能技术，和特定的挑战主题，06-EB-109：模型驱动的生物医学技术开发。计算椎间盘内部应力和应变的结构模型对于研究椎间盘损伤、撕裂和失败的机制至关重要。此外，准确的模型将提供理解，以预测手术干预，器械植入和组织工程的后果。不幸的是，目前可用的椎间盘模型缺乏准确预测力学行为的保真度。本建议的目的是开发一个基于图像的光盘模型，结合组织的不均匀，各向异性和非线性材料特性。本挑战提案中描述的拟议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）之间创建四个全职职位。