Prolonged alterations to muscle following knee surgery and physical therapy

描述(由申请人提供)：这是肯塔基大学物理治疗助理教授Brian Noehren博士的K23奖项申请。诺伦博士正在把自己塑造成一名年轻的研究员，专注于以患者为导向的临床研究，致力于研究康复策略如何恢复患者的肌肉功能，最终改善他们的长期功能结果。K-23奖项将为诺伦博士提供必要的支持，让他成为一名多产的独立科学家，能够在受伤和随后的物理治疗中测量肌肉的细胞和形态属性。这些技能的发展将使他能够在未来的研究中评估新的和新颖的康复治疗的有效性，以改善肌肉功能和关节负荷。为了实现这些目标，诺伦博士组建了一个由各自领域公认的领导者组成的导师团队。该团队由健康科学学院研究部副院长夏洛特·彼得森博士和三位共同导师领导：肌肉健康和疾病专家Karyn Esser博士，肌肉结构和生物物理学专家Bruce Damon博士，以及临床试验专家Leslie Crofford博士。前交叉韧带重建超过20%-40%后，股四头肌力量下降发生在物理治疗结束、个人开始恢复对肌肉要求更高的活动的关键时刻。在这段时间内股四头肌力量的下降与较差的结果相关。到目前为止，对康复后肌肉力量的测量仅限于大体测量，对股外侧肌等股四头肌的个体头部对手术的反应知之甚少。因此，我们提出了两个具体的目标：(目标1)评估重建前交叉韧带康复前后股四头肌(股外侧肌)肌束长度、羽状角和生理横截面积。(目的2)通过量化股四头肌纤维类型、纤维横截面积和完成前交叉韧带重建后的纤维化来描述肌肉形态。在目标1中，诺伦博士将使用他的导师之一达蒙博士建立的DTI-MRI来测量与最大力量产生密切相关的肌肉特性。在目标2中，他将在彼得森博士的实验室进行组织学和免疫组织化学分析，从目标1的同一组股外侧肌中提取肌肉活检组织，以分类对肌肉纤维横截面积、纤维类型以及脂肪生长和纤维化的适应。Esser博士将协助实现这一目标的培训和对结果的解释。AIMS将把来自非侵入性成像的数据与肌肉的详细细胞分析结合起来，这将为康复实践提供信息。此外，克罗福德博士还将提供将结果转化为临床研究、临床试验和数据分析的培训。

DESCRIPTION (provided by applicant): This is a K23 award application for Dr. Brian Noehren, an Assistant Professor of Physical Therapy at the University of Kentucky. Dr. Noehren is establishing himself as a young investigator focused on patient orientated clinical research dedicated to the study of how rehabilitation strategies restore muscle function in patients to ultimately improve their long term functional outcomes. The K-23 award would provide Dr. Noehren the needed support to become a productive independent scientist who is able to measure the cellular and morphological properties of muscle in response to injury and subsequent physical therapy. Development of these skills will allow him in future studies to assess the effectiveness of new and novel rehabilitation treatments to improve muscle function and joint loading. To achieve these goals Dr. Noehren has assembled a mentorship team of acknowledged leaders in their respective fields. This team is led by the senior mentor Dr. Charlotte Peterson, Associate Dean of Research, College of Health Sciences, and three co-mentors: Dr. Karyn Esser, an expert in muscle health and disease Dr. Bruce Damon, who is an expert in muscle structure and biophysics, and Dr. Leslie Crofford, an expert clinical trialist. Quadriceps strength reductions after an anterior cruciate ligament reconstruction of greater than 20- 40% occur at a critical time when physical therapy is ending and the individual begins to return to activities that require higher muscular demands. The reduction in quadriceps strength during this period of time has been associated with poorer outcomes. The measurement of muscular strength after rehabilitation to date has been limited to gross measurements, with little known of how the individual heads of the quadriceps such as the Vastus Lateralis respond to surgery. Therefore we propose two specific aims: (Aim 1) Assess the quadriceps muscle (vastus lateralis) fascicle length, pennation angle, and physiological cross sectional area before and after rehabilitation for ACL reconstruction. (Aim 2) Characterize muscle morphology through quantification of quadriceps muscle fiber type, fiber cross sectional area, and fibrosis after completing rehabilitation for an ACL reconstruction. In Aim 1, Dr. Noehren will use DTI-MRI established by one his mentors, Dr. Damon, to measure muscle properties strongly linked to maximum force production. In Aim 2, he will perform histo and immuno-histiochemical analysis in Dr. Peterson's laboratory of muscle biopsies taken from the Vastus Lateralis of the same group from Aim 1 to categorize the adaptations to muscle fiber cross sectional area, fiber type, as well as fatty in-growth and fibrosis. Dr. Esser will assist with training for this aim and the interpretation of the results. The aims will couple data from non invasive imaging with detailed cellular analysis of muscle which will inform rehabilitative practice. In addition Dr. Crofford wil provide the training of translating the results into clinical research, clinical trials, and data analysis.