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奖申请。Noehren博士是一名年轻的研究人员，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奖将为Noehren博士提供必要的支持，使他成为一名富有成效的独立科学家，能够测量肌肉对损伤和随后的物理治疗的细胞和形态特性。这些技能的发展将使他在未来的研究中评估新的和新的康复治疗方法的有效性，以改善肌肉功能和关节负荷。为了实现这些目标，Noehren博士组建了一个由各自领域公认的领导者组成的指导团队。该团队由高级导师、健康科学学院研究副院长Charlotte Peterson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博士和临床试验专家Leslie Crofford博士。前交叉韧带重建后，股四头肌力量下降超过20- 40%发生在物理治疗结束，个体开始恢复需要更高肌肉需求的活动的关键时刻。在此期间，股四头肌力量的减少与较差的预后有关。迄今为止，对康复后肌肉力量的测量仅限于粗略测量，对股外侧肌等股四头肌的个别头部对手术的反应知之甚少。因此，我们提出了两个具体目标：（目的1）评估前交叉韧带重建康复前后的股四头肌（股外侧肌）束长度、夹角和生理横截面积。（目的2）在完成ACL重建康复后，通过量化股四头肌肌纤维类型、纤维横截面积和纤维化来表征肌肉形态。在Aim 1中，Noehren博士将使用他的导师Damon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Aim 2中，他将在Peterson博士的实验室对Aim 1中同一组的股外侧肌的肌肉活检进行组织学和免疫组织化学分析，以分类对肌纤维横截面积、纤维类型以及脂肪生长和纤维化的适应。Esser博士将协助为此目的进行培训并对结果进行解释。目的是将非侵入性成像数据与详细的肌肉细胞分析相结合，这将为康复实践提供信息。此外，他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.