Contact mechanics, neuromuscular control, and cartilage composition in knee OA

描述(由申请人提供)：日常活动中的机械负荷在膝骨性关节炎(OA)的发生和发展中起着关键作用。利用通过母公司研究(AR R0146905-11)获得的丰富的定量MRI数据集，该项目利用多尺度方法通过评估软骨成分变化、关节接触力学、全身神经肌肉动力学和功能表现来了解膝骨性关节炎的疾病过程。105名患有和不患有膝骨性关节炎的受试者将接受运动学核磁共振、功能任务期间的神经肌肉控制测试、功能表现指标以及软骨和半月板成分的定量磁共振检查。提出了横断面(OA与对照)和纵向(基线、1年、2年和3年随访)的目标。随着体内关节接触力学和神经肌肉模式的增加，数据集将变得非常全面，从而具有无与伦比的能力来查看影响膝骨性关节炎发病和进展的多个指标。据推测，由此产生的跨组织成分到功能的综合指标将为疾病的早期检测和进展预后提供更强大的生物标志物。这些知识将直接转化到临床上，因为力量、运动和肌肉激活等神经肌肉因素可以通过有针对性的矫形和康复干预来修改；而像排列不良或关节接触力学异常的结构性因素可能会通过手术干预而受到影响。具体目标1：a)使用运动学MR技术量化对照组和膝关节骨性关节炎患者关节接触力学的差异，并建立关节接触力学与软骨和半月板T1a和T2松弛时间、形态分级、放射学和功能测量的相关性。B)量化对照组和膝关节骨性关节炎患者在神经肌肉控制方面的差异；并确定行走过程中的神经肌肉控制与关节接触力学、软骨和半月板T1a和T2松弛时间、形态分级、放射学和功能测量之间的关系。具体目标2：a)测定对照组和膝关节骨性关节炎受试者三年来关节接触力学的纵向变化，以及对照组和膝关节骨性关节炎受试者在步行过程中神经肌肉控制的三年纵向变化。B)确定基线关节接触力学和神经肌肉控制在确定疾病进展方面的预测能力。

DESCRIPTION (provided by applicant): Mechanical loading during daily activities plays a critical role in the onset and progression of knee osteoarthritis (OA). Taking advantage of the rich quantitative MRI dataset acquired through the parent study (AR R0146905-11), this project utilizes a multi-scale approach towards understanding the knee OA disease process by evaluating cartilage compositional changes, joint contact mechanics, whole-body neuromuscular dynamics and functional performance. One hundred-five subjects with and without knee OA will undergo kinematic-MRI, neuromuscular control testing during functional tasks, metrics of functional performance, and quantitative MR for cartilage and meniscus composition. Both cross-sectional (OA vs. controls) and longitudinal (baseline, 1- year, 2-year, and 3-year follow-up) aims are proposed. With the addition of in-vivo articular contact mechanics and neuromuscular patterns, the dataset will become extremely comprehensive giving an unparalleled ability to look at multiple metrics affecting incidence and progression in knee OA. It is hypothesized that the resulting combined metrics, across scales from tissue composition to function, will provide stronger biomarkers for early detection and progression prognosis of the disease. This knowledge will be directly translatable to the clinic since neuromuscular factors like strength, movement, and muscle activation are modifiable through targeted orthotic and rehabilitation interventions; and structural factors like malalignment or abnormal articular contact mechanics may be influenced through surgical interventions. Specific Aim 1: A) To quantify differences in articular contact mechanics using kinematic MR in controls and subjects with knee OA; and to establish the correlation of articular contact mechanics with metrics from cartilage and meniscus T1A and T2 relaxation times, morphological grades, radiographic and functional measures. B) To quantify differences in neuromuscular control in controls and subjects with knee OA; and to determine the relationship between neuromuscular control during walking and articular contact mechanics, cartilage and meniscus T1A and T2 relaxation times, morphological grades, radiographic and functional measures. Specific Aim 2: A) To determine the longitudinal change over three years in articular contact mechanics in controls and subjects with knee OA; and to determine the longitudinal change over three years in neuromuscular control during walking in controls and subjects with knee OA. B) To determine the predictive capability of baseline articular contact mechanics and neuromuscular control at determining disease progression.