Mechanics and MRI T2* mapping of tendon extracellular matrix under differential swelling

Objectives Changes in biophysical properties of the extracellular matrix (ECM) are often indicative of disease presence and progression. Although this poses problems in many clinical situations, only few technologies are available that allow in vivo, non-invasive, monitoring of ECM structural and mechanical properties. Tendinopathies are a primary reason for which patients seek musculoskeletal health care and can be characterized by tissue swelling. We investigated the potential of magnetic resonance imaging (MRI) T2* mapping to identify local changes in tendon ECM mechanical properties due to differential swelling situations.

Methods Fresh Achilles tendons from eight healthy sheep (Merino, female, 4+ years old) were excised after euthanasia. Six cylindrical samples were cut from the mid-portion of each tendon. Isotonic and hypotonic conditions were created by immersing tendon samples in phosphate buffer saline and water, respectively, for 24 hours. Uniaxial compression testing was used to quantify the elastic modulus E and the viscoelastic stress relaxation half time tau_(1/2). A clinical 3 T MRI scanner was used for mapping of T1 and T2* relaxation times, a surrogate marker for water content. The ECM properties were monitored for fresh and swollen states. Results were evaluated using two-tailed paired t-tests, and a p- value < 0.05 was considered significant.

Results and Conclusion In isotonic solution, the ECM displayed lower E and did not change in terms of tau_(1/2). Both T1 and T2* increased. Higher T1 and T2* can be associated with an elevated amount of unbound water. Such ECM changes mimic characteristics of tendinopathies involving swelling and inferior mechanics, and showed similar magnitudes of mass uptake as previously reported. In hypotonic solution, the ECM displayed higher E and faster tau_(1/2). T1 increased but there was no observable change in T2*. These MRI results indicated no change in unbound water while significant mass uptake was recorded, which could be relevant for identifying tissue contractures. Such ECM degenerative changes of skin or other soft tissues have been shown to be characterized byresemble higher rigidity and water binding proteoglycan content compared to healthy tissues.

Our study showed that ECM properties can be smoothly modified from the fresh state by immersion into isotonic and hypotonic solutions. Exposure to such conditions resulted in differential swelling and presumably different extents of water binding in the collagen and proteoglycan structures of the ECM. These modifications of the ECM were intended to reflect traits of ECM degeneration. This study illustrates that combined MRI T1 and T2* mapping may represent a valuable diagnostic tool to monitor, non-invasively, local changes in tissue mechanics that occur at the onset of diseases that involve swelling, water uptake and associated tissue alterations.

Stichwörter ECM, mechanics, MRI, tendinopathy

Publication History

Article published online:
15 October 2020