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

项目总结 肩袖撕裂是一种常见的肩部疾病，影响约40%的人。 60岁。这种情况令人痛苦、虚弱，并降低了生活质量。尽管它们很普遍，但 肩袖撕裂的病因尚不完全清楚，但普遍认为与外部因素有关。 (即肩部运动时的肌腱撞击)、内在因素(即肌腱变性)和/或 过度使用。这些因素在动物模型中得到了广泛的研究，这为 每个因素都会导致肩袖病理改变。然而，这些发现尚未在#年得到证实。 人类研究很大程度上是因为难以准确和可靠地评估内在因素和 在人类中过度使用。最终，对人类肩袖病理的病因学的了解将继续存在。 如果没有一个模型来描述每个因素在肩袖病理中的作用，就很难做到。目标 建议的研究包括：1)开发一个初步的多变量模型，对影响进行分类 外源性、内源性和过度使用因素对无症状个体肩袖病理的影响(K99)； 使用其他无症状参与者(R00)扩展模型；以及3)扩展模型以包括 有症状的参与者(R00)。我们的方法将是量化肩部的运动和撞击 (外在因素)经双平面x射线成像，肩袖退变(内在因素)经剪切波 弹性成像，过度使用因素，通过一个新的估计终生肩部暴露，以及严重的 通过诊断成像进行肩袖病理检查。我们将调查病因与疾病之间的关系 采用分类和回归树分析影响肩袖病变的因素。建议进行的研究 职业发展计划的重点是提供必要的指导， 课程学习和研究培训，让我成为一名独立的、有影响力的研究人员。这个 K99阶段的目标是：1)获得先进的生物力学数据收集方法方面的培训 分析评估外在、内在和过度使用因素在肩袖病因中的作用 病理学；2)建立一个初步的多变量模型，描述外在的、内在的和 过度使用因素对肩袖病理的影响；以及3)在一项受人尊敬的研究中获得终身教职- 密集的大学。R00阶段的目标是：1)独立进行R00阶段研究 通过运用在K99阶段学到的技能；2)建立多学科研究 与工程师、矫形外科医生和物理治疗师合作；3)领导资金充足和 生产性研究实验室；以及4)以K99/R00研究成果为基础，确保独立 R01基金。再加上亨利福特健康系统丰富的研究环境，建议的 职业发展计划将确保我拥有从事独立研究的独特技能 职业生涯，产生可靠和有影响力的研究，并帮助培养下一代科学家。

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.