In Vivo Imaging-Based Multiscale Modeling of Normal and Atrophied Human Lower Leg

基于体内成像的正常和萎缩人类小腿的多尺度建模

• 批准号: 8513915
• 负责人: Shantanu Sinha
• 金额: $ 57.79万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-15 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8513915
• 关键词: Accounting; Address; Affect; Architecture; Area; Atrophic; Behavior; Biological; Biomedical Engineering; Chronic; Clinical; Complex; Computer Simulation; Connective Tissue; Data; Development; Devices; Dimensions; Disease; Disuse Atrophy; Elements; Fascicle; Goals; Guidelines; Heterogeneity; Human; Image; Imaging Techniques; Incentives; Individual; Intramuscular; Joints; Knee; Leg; Length; Limb structure; Link; Literature; Location; Lower Extremity; Measurement; Measures; Mechanics; Modeling; Morphology; Muscle; Muscle Contraction; Muscle Fibers; Muscle strain; Muscular Atrophy; Muscular Dystrophies; Musculoskeletal; Musculoskeletal Diseases; Musculoskeletal System; Myopathy; Operative Surgical Procedures; Output; Parents; Pathology; Patients; Pattern; Performance; Physiological; Physiology; Play; Property; Protocols documentation; Recovery; Rehabilitation therapy; Relative (related person); Research Personnel; Rest; Role; Rupture; Sarcomeres; Shapes; Simulate; Skeletal Muscle; Staging; Structure; Suspension substance; Suspensions; System; Tendon structure; Therapeutic; Tissues; Torque; Translating; Triceps Brachii Muscle; Variant; Work; achilles tendon; ankle joint; aponeurosis; base; calcaneum; design; foot; in vivo; multi-scale modeling; muscular structure; neuromuscular; novel; repaired; simulation

DESCRIPTION (provided by applicant): This is the resubmission of a Competitive Renewal application of a parent RO1 whose primary goal was to understand how the structural design features of the human Triceps Surae Complex define its functional properties in vivo. Development of novel devices and imaging techniques allowed non-invasive in-vivo measurement of critical anatomical features that affect function. These consistently revealed heterogeneous strain occurring along the aponeurosis, tendon and muscle fascicles and variation of mechanical gear ratio along the length of the muscle. Subsequent finite element modeling based on these data clearly demonstrated that current models of human neuromuscular in vivo function are inadequate. It is now evident that complex intramuscular mechanics play a critical role in the muscle forces generated in active muscles. To explain the disproportionate decrease in force relative to loss of muscle volume in clinical cases of atrophy and similar pathologies, we hypothesize that: (1) A consistent and reliable specific tension (force per PCSA) of human skeletal muscle can be derived by defining the mechanical heterogeneity of musculoskeletal tissues over multi-scale dimensions; and (2) Changes in selected components of this mechanical complex within and among these musculoskeletal tissues contribute significantly to the loss of muscle force potential as occurs in "disuse" atrophy. 30 normal subjects will be imaged from which 12 with the broadest range of muscle shapes will be chosen for inducement of controlled atrophy by Unilateral Limb Suspension followed by rehabilitation. A highly integrated array of imaging techniques will characterize comprehensively, the multi- component musculoskeletal (MSK) architecture and function of the lower leg, in normal, atrophied and at various stages of recuperation in these subjects and in 8 patients recovering from Achilles Tendon Rupture. Specific Aim (SA)-1 will measure the MSK parameters: (A) 3D volume rendered images of the muscle complex, (B) Distribution of tendon, aponeurosis and intra-muscular connective tissues, (C) Muscle fiber orientation throughout the muscles and (D) total MVC. SA-2 will define the relative contribution to losses of torque due to atrophy-induced changes from: (A) Muscle deformation, (B) Muscle fiber strain, (C) Aponeurosis strain and shear, (D) Tendon excursion and, (E) Calcaneus displacement. (SA-3) Subject-specific image-driven mesh-free (A) Component Level, and (B) Multi- scale, multi-component Systems Level models will be used to predict strain distribution, ankle joint displacement and total joint force. Predictions of the model as to the sensitivity of the total joint force and other output variables to changes in material properties arising from various stages between normal and atrophied states will be compared with the experimental observations in SA-2. Following the guidelines of PA-07-279, a "multi-disciplinary integrative, systems approach" will be applied "to understand (the) important biological, bioengineering problem" of the complex muscle structure-function interactions. This has far ranging clinical potential for tailored management of patients with musculoskeletal disease such as chronic muscle disuse, muscular dystrophy and spasticity.

描述（由申请人提供）：这是对父型RO1的竞争更新应用的重新提交，其主要目标是了解人类三头肌苏拉（Surae）复合物的结构设计特征如何在体内定义其功能性能。新型设备和成像技术的开发允许对影响功能的临界解剖学特征进行非侵入性测量。这些始终显示出沿着肌肌剧，肌腱和肌肉束以及沿肌肉长度的机械齿轮比的变化的异质菌株。随后基于这些数据的有限元建模清楚地表明，人体神经肌肉在体内功能的当前模型不足。现在很明显，复杂的肌内力学在活性肌肉中产生的肌肉力中起关键作用。 为了解释临床萎缩和类似病理学的肌肉体积损失的力量的不成比例减少，我们假设：（1）可以通过定义肌肉骨骼骨骼骨骼骨骼组织的机械异质性过度多数的肌肉的机械异质性来得出人类骨骼肌的一致和可靠的特异性张力（每PCSA）。 （2）这些肌肉骨骼组织内部和中间这种机械复合物的选定成分的变化对肌肉力量的损失显着贡献，因为“废除”萎缩时会发生。将成像30个正常受试者，其中12个具有最广泛的肌肉形状的受试者将被选中以通过单侧肢体悬浮液进行诱导控制萎缩，然后进行康复。高度集成的成像技术将全面地表征，在正常，萎缩，萎缩和在这些受试者的各个恢复阶段，在这些受试者的各个阶段以及从阿喀琉斯肌腱破裂中恢复的8例患者中，下腿的多组分肌肉骨骼（MSK）结构和功能。特定目标（SA）-1将测量MSK参数：（a）肌肉复合物的3D体积图像，（b）肌腱，阿替尿和肌肉内结缔组织的分布，（c）在整个肌肉和（d）总MVC的整个肌肉纤维方向。 SA-2将定义由于萎缩引起的变化引起的扭矩损失的相对贡献：（a）肌肉变形，（b）肌肉纤维菌株，（c）阿替尿症菌株和剪切，（d）肌腱偏移和（e）卡通烷置换。 （SA-3）特定于特定图像驱动的网格（a）组件水平，以及（b）多尺度，多组分系统级别模型将用于预测应变分布，踝关节位移和总关节力。该模型对总关节力和其他输出变量对正常状态和萎缩状态之间各个阶段产生的材料特性变化的敏感性的预测将与SA-2中的实验观察结果进行比较。遵循PA-07-279的指南，将采用“多学科综合，系统方法”来了解复杂肌肉结构 - 功能相互作用的重要生物学，生物工程问题。这对于量身定制的肌肉骨骼疾病患者（例如慢性肌肉消失，肌肉营养不良和痉挛）的临床潜力很大。