Investigating the Multi-factorial Etiology of Rotator Cuff Pathology in Human Subjects

项目摘要 肩袖撕裂是一种常见的肩关节疾病，在过去的20年中， 60岁。这种情况是痛苦的，衰弱的，并降低生活质量。尽管其盛行， 肩袖撕裂的病因尚未完全清楚，但通常认为与外在因素有关 (i.e.肩关节运动过程中的肌腱撞击）、内在因素（即肌腱退化）和/或 过度使用这些因素已经在动物模型中进行了广泛的研究，这为以下研究提供了支持： 每一个因素都导致了旋转套的病变。然而，这些发现尚未得到证实， 人类研究主要是因为难以准确可靠地评估内在因素， 在人类中过度使用。最终，了解人类肩袖病理的病因将仍然是 没有一个模型来描述每个因素在肩袖病理中的作用是困难的。目标 拟议的研究是：1）开发一个初步的多变量模型， 无症状个体中肩袖病理学的外在、内在和过度使用因素（K99）; 2） 使用额外的无症状参与者（R 00）扩展模型;以及3）扩展模型以包括 症状参与者（R 00）。我们的方法是量化肩部运动和撞击 （外在因素）通过双平面X线成像，肩袖退变（内在因素）通过剪切波 弹性成像，过度使用因素，通过一种新的估计终身肩部暴露，和严重程度， 通过诊断成像检查肩袖病理。我们将调查病因学之间的关系， 因素和肩袖病理使用分类和回归树分析。拟议的研究 是为提供必要的指导而制定的职业发展计划的基石， 课程和研究培训，使我成为一个独立和有影响力的研究人员。的 K99阶段的目标是：1）获得生物力学数据收集先进方法的培训 评估外在、内在和过度使用因素在肩袖病因学中的作用 病理学; 2）建立一个初步的多变量模型，描述外在的，内在的， 肩袖病理学的过度使用因素;以及3）在受人尊敬的研究中获得终身职位- 密集型大学R 00阶段的目标是：1）独立进行R 00阶段研究 通过实施在K99阶段学到的技能; 2）建立多学科研究 与工程师，整形外科医生和物理治疗师合作; 3）领导一个资金充足， 生产性研究实验室;以及4）在K99/R 00研究成果的基础上， R 01融资再加上亨利福特健康系统丰富的研究环境， 职业发展计划将确保我有一个独特的技能，以追求独立的研究 职业生涯，产生健全和有影响力的研究，并帮助准备下一代科学家。

PROJECT SUMMARY A rotator cuff tear is a common shoulder condition that affects approximately 40% of individuals over the age of 60. This condition is painful, debilitating, and reduces quality of life. Despite their prevalence, the etiology of rotator cuff tears is not fully understood but is generally believed to involve extrinsic factors (i.e. tendon impingement during shoulder motion), intrinsic factors (i.e. tendon degeneration), and/or overuse. These factors have been studied extensively in animal models, which have provided support for each factor contributing to rotator cuff pathology. However, these findings have not yet been confirmed in human studies largely because of the difficulty in accurately and reliably assessing intrinsic factors and overuse in humans. Ultimately, understanding the etiology of rotator cuff pathology in humans will remain difficult without a model that characterizes the role of each factor in rotator cuff pathology. The objectives of the proposed studies are to: 1) develop a preliminary multivariable model classifying the effects of extrinsic, intrinsic, and overuse factors on rotator cuff pathology in asymptomatic individuals (K99); 2) extend the model with additional asymptomatic participants (R00); and 3) expand the model to include symptomatic participants (R00). Our approach will be to quantify shoulder motion and impingement (extrinsic factors) via biplane x-ray imaging, rotator cuff degeneration (intrinsic factors) via shear wave elastography, overuse factors via a novel estimate of lifetime shoulder exposure, and the severity of rotator cuff pathology via diagnostic imaging. We will investigate the relationship between the etiological factors and rotator cuff pathology using classification and regression tree analysis. The proposed studies are the keystone of a career development plan developed to provide the necessary mentorship, coursework, and research training for me to become an independent and impactful researcher. The goals of the K99 phase are to: 1) obtain training in advanced methods of biomechanical data collection and analysis to assess the roles of extrinsic, intrinsic, and overuse factors in the etiology of rotator cuff pathology; 2) develop a preliminary multivariable model describing the role of extrinsic, intrinsic, and overuse factors on rotator cuff pathology; and 3) obtain a tenure track position at a respected research- intensive university. The goals of the R00 phase are to: 1) independently conduct the R00 phase study by implementing the skills learned during the K99 phase; 2) establish multi-disciplinary research collaborations with engineers, orthopaedic surgeons, and physical therapists; 3) lead a well-funded and productive research laboratory; and 4) build upon the K99/R00 research findings to secure independent R01 funding. Together with the rich research environment at Henry Ford Health System, the proposed career development plan will ensure that I have a unique skillset to pursue an independent research career, produce sound and impactful research, and help prepare the next generation of scientists.