# Quadriceps Muscle Quality: A Post-Injury Determinant of Knee Function and Health

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $265,470

## Abstract

Abstract
Persistent quadriceps muscle dysfunction following anterior cruciate ligament (ACL) injury and reconstruction
(ACLR) is a critical clinical concern impacting the success of postoperative rehabilitation and prognosis of long-
term joint health. Our novel working hypothesis is that worse quadriceps muscle quality, caused by a progressive
increase in non-contractile tissue within the muscle, post-ACL injury and ACLR is a critical and understudied
mechanism underlying poor clinical outcomes. There is a significant scientific gap in our understanding of the
mechanistic pathway linking changes in quadriceps muscle quality to poor clinical outcomes. Our preliminary
work using ultrasonography to assess changes in muscle quality supports our working hypothesis, in that
patients with an ACL injury demonstrate muscle tissue image signal changes consistent with increased non-
contractile tissue makeup in the first 3 months post-ACLR. Furthermore, ultrasonographic muscle tissue signal
changes are associated with lesser knee extensor strength and worse physical performance (i.e., hop testing).
Unfortunately, rigorous studies to test our working hypothesis have not been conducted to comprehensively
evaluate the effect of ACL injury on muscle quality and the impact of poorer muscle quality on clinical outcomes.
Recent magnetic resonance imaging (MRI) innovations now allow for high-precision and rapid evaluation of
muscle quality throughout the entire muscle volume and in individual quadricep heads. We can be opportunistic
and leverage an ongoing rehabilitation-based parent clinical trial already collecting critical clinical outcomes of
knee extensor strength, gait biomechanics, physical performance and patient-reported outcomes (PRO), and
tibiofemoral cartilage composition at preoperative, and 1-, 6-, and 12-month post-ACLR timepoints. We are
proposing to test our working hypothesis with an ancillary R21 by conducting the following specific aims: 1)
determine longitudinal changes in quadriceps muscle quality following ACL injury and ACLR preoperatively and
at 1-, 6- and 12-months post-ACLR; and 2) determine the associations between changes in muscle quality and
a) knee extensor strength; b) gait biomechanics; c) PRO and physical performance; and d) tibiofemoral cartilage
composition. Our study is innovative as: 1) we are testing a novel hypothesis that quadriceps muscle quality
changes early post-ACL injury and that it is a critical mechanism associated with poor clinical outcomes; 2) we
are utilizing a novel MRI technique capable of collecting highly-sensitive measures of muscle quality in individual
heads of the quadriceps throughout the entire muscle volume; and 3) associations between muscle quality and
a comprehensive host of clinical outcomes (i.e. knee extensor strength, gait biomechanics, physical performance
and PRO, and tibiofemoral cartilage composition) can be evaluated as part of the ancillary R21. The proposed
R21 is significant as identif...

## Key facts

- **NIH application ID:** 10894266
- **Project number:** 5R21AR083163-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Brian Pietrosimone
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $265,470
- **Award type:** 5
- **Project period:** 2023-07-26 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894266

## Citation

> US National Institutes of Health, RePORTER application 10894266, Quadriceps Muscle Quality: A Post-Injury Determinant of Knee Function and Health (5R21AR083163-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10894266. Licensed CC0.

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