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）：此申请介绍了广泛的挑战领域（06）启用技术，而特定的挑战主题，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计算内部应力和菌株是研究损伤机制和失败机制的必要技术。此外，准确的模型提供了理解，以预测手术干预，装置植入和组织工程的后果。该提案解决了对椎间盘进行建模的挑战。在过去的三十年中，有限元模型已被证明对研究光盘力学很有价值。但是，当前可用的光盘模型具有三个重要的局限性，在此提案中将解决，以提高忠诚度以预测机械行为。首先，输入模型的测得的纤维纤维（AF）特性基于切除的组织测试。切除组织会破坏纤维结构，从而将伪影引入材料特性测量中，并且不代表盘组成和微体系结构的逐渐改变所反映的不均匀性。其次，切除组织样品消除了子结构之间的界面。第三，当前光盘模型使用“电缆”元素，这些元素嵌入了AF的各向同性固体元素中。表面上这代表AF结构；但是，AF组成和微体系结构是复杂的，需要更好地反映AF各向异性，非线性和不均匀性的组成式公式。该提案的目的是开发一个基于图像的光盘模型，该模型结合了组织的不均匀，各向异性和非线性材料特性。我们将使用复杂的启用技术获得具有具有空间分布的材料特性的3D结构模型。 AIM 1：将已建立的2D MRI扩展到负载下光盘的高分辨率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。 AIM 2：在多轴加载配置下进行图像人盘，包括压缩，弯曲和扭转，并使用最新的差异图像登记来计算3D应变图。 AIM 3：将逆方法应用于已建立的构造配方和测量的应变图以确定材料特性。通过预测在属性计算中未使用的加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重复计算研究，以进行参数回归。完成这项研究后，由于原纤维组件和外部纤维外矩阵的微结构贡献以及对二心体结构之间的相互作用的响应，我们将能够准确预测椎间盘内的应力和菌株。确定原位材料特性是对切除组织测试中伪影的当前局限性和统计界面的破坏的创新解决方案。这项工作的重要性在于开发出宝贵的工具，用于精确建模光盘力学，这既是理解盘的力学故障又是对其进行处理的核心。该系统最初将应用于尸体人体组织。但是，长期成像的进展可能允许扩展到体内应用以及特定于患者的建模和分析。经济影响，该挑战提案中描述的拟议实验将在宾夕法尼亚大学（2.5个博士后研究人员，0.2技术人员）和明尼苏达大学（1名研究生，0.5个研究生，0.5博士后研究人员）之间建立四个全职职位。宾夕法尼亚大学医学院是创建新知识和疗法以改善人类健康以及培训下一代科学领导者的国际认可的领导者。为了实现这些目标，Upenn医学院在整个宾夕法尼亚州，新泽西州和特拉华州都广泛地扩展了其经济影响。最近的研究将37,000个工作岗位和54亿美元的经济活动归因于2008年的宾夕法尼亚医学。作为明尼苏达州唯一的研究大学，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力远远广泛，有21,500多个工作与该大学授予的研究补助金直接相关。该申请涉及广泛的挑战领域（06）促成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。计算圆盘内部应力和应变的结构模型对于研究椎间盘损伤，泪液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，装置植入和组织工程的后果。不幸的是，当前可用的光盘模型缺乏准确预测机械行为的忠诚度。该提案的目的是开发一个基于图像的光盘模型，该模型结合了组织的不均匀，各向异性和非线性材料特性。该挑战提案中描述的拟议实验将在宾夕法尼亚大学（2.5个博士后研究人员，0.2技术人员）和明尼苏达大学（1名研究生，0.5个研究生，0.5博士后研究人员）之间建立四个全职职位。