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.
Identification of the underlying cellular and myofiber adaptations that contribute to the loss of quadriceps strength after an ACL reconstruction is essential to develop improved physical therapy interventions and functional outcomes.
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