T1ρ imaging as a non-invasive assessment of collagen remodelling and organization in human skeletal muscle after ligamentous injury

Brian Noehren, Peter A. Hardy, Anders Andersen, Camille R. Brightwell, Jean L. Fry, Moriel H. Vandsburger, Katherine L. Thompson, Christopher S. Fry

Research output: Contribution to journalArticlepeer-review

Abstract

Abstract: Dysregulation and fibrosis of the extracellular matrix (ECM) in skeletal muscle is a consequence of injury. Current ECM assessment necessitates muscle biopsies to evaluate alterations to the muscle ECM, which is often not practical in humans. The goal of this study was to evaluate the potential of a magnetic resonance imaging sequence that quantifies T1ρ relaxation time to predict ECM collagen composition and organization. T1ρ imaging was performed and muscle biopsies obtained from the involved and non-involved vastus lateralis muscle on 27 subjects who had an anterior cruciate ligament (ACL) tear. T1ρ times were quantified via monoexponential decay curve fitted to a series of T1ρ-weighted images. Several ECM indices, including collagen content and organization, were obtained using immunohistochemistry and histochemistry in addition to hydroxyproline. Model selection with multiple linear regression was used to evaluate the relationships between T1ρ times and ECM composition. Additionally, the ACL-deficient and healthy limb were compared to determine sensitivity of T1ρ to detect early adaptations in the muscle ECM following injury. We show that T1ρ relaxation time was strongly associated with collagen unfolding (t = 4.093, P = 0.0007) in the ACL-deficient limb, and collagen 1 abundance in the healthy limb (t = 2.75, P = 0.014). In addition, we show that T1ρ relaxation time is significantly longer in the injured limb, coinciding with significant differences in several indices of collagen content and remodelling in the ACL-deficient limb. These results support the use of T1ρ to evaluate ECM composition in skeletal muscle in a non-invasive manner. (Figure presented.). Key points: Dysregulation and fibrotic transformation of the skeletal muscle extracellular matrix (ECM) is a common pathology associated with injury and ageing. Studies of the muscle ECM in humans have necessitated the use of biopsies, which are impractical in many settings. Non-invasive MRI T1ρ relaxation time was validated to predict ECM collagen composition and organization with aligned T1ρ imaging and biopsies of the vastus lateralis in the healthy limb and anterior cruciate ligament (ACL)-deficient limb of 27 subjects. T1ρ relaxation time was strongly associated with collagen abundance and unfolding in the ACL-deficient limb, and T1ρ relaxation time was strongly associated with total collagen abundance in the healthy limb. T1ρ relaxation time was significantly longer in the ACL-deficient limb, coinciding with significant increases in several indices of muscle collagen content and remodelling supporting the use of T1ρ to non-invasively evaluate ECM composition and pathology in skeletal muscle.

Original languageEnglish
Pages (from-to)5229-5242
Number of pages14
JournalJournal of Physiology
Volume599
Issue number23
DOIs
StatePublished - Dec 1 2021

Bibliographical note

Funding Information:
Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Numbers R01 AR071398, R01 AR072061, and R01 AR071398‐04S1, as well as by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under award Number P41EB015893, and the National Institutes of Health National Centre for Advancing Translational Sciences through award number UL1TR001998. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2021 The Authors. The Journal of Physiology © 2021 The Physiological Society

Keywords

  • T1rho
  • extracellular matrix
  • magnetic resonance imaging
  • muscle fibrosis

ASJC Scopus subject areas

  • Physiology

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