MRI-derived Articular Cartilage Strains Predict Patient-Reported Outcomes Six Months Post Anterior Cruciate Ligament Reconstruction

Abstract

Key terms Multicontrast and Multiparametric, Magnetic Resonance Imaging, Osteoarthritis, Functional Biomechanical Imaging, Knee Joint Degeneration

What is known about the subject: dualMRI has been used to quantify strains in a healthy human population in vivo and in cartilage explant models. Previously, OA severity, as determined by histology, has been positively correlated to increased shear and transverse strains in cartilage explants.

What this study adds to existing knowledge: This is the first in vivo use of dualMRI in a participant demographic post-ACL reconstruction and at risk for developing osteoarthritis. This study shows that dualMRI-derived strains are more significantly correlated with patient-reported outcomes than any MRI relaxometry metric.

Background Anterior cruciate ligament (ACL) injuries lead to an increased risk of osteoarthritis, characterized by altered cartilage tissue structure and function. Displacements under applied loading by magnetic resonance imaging (dualMRI) is a novel MRI technique that can be used to quantify mechanical strain in cartilage while undergoing a physiological load.

Purpose To determine if strains derived by dualMRI and relaxometry measures correlate with patient-reported outcomes at six months post unilateral ACL reconstruction.

Study Design Cohort study

Methods Quantitative MRI (T2, T2*, T1ρ) measurements and transverse, axial, and shear strains were quantified in the medial articular tibiofemoral cartilage of 35 participants at six-months post unilateral ACL reconstruction. The relationships between patient-reported outcomes (WOMAC, KOOS, MARS) and all qMRI relaxation times were quantified using general linear mixed-effects models. A combined best-fit multicontrast MRI model was then developed using backwards regression to determine the patient features and MRI metrics that are most predictive of patient-reported outcome scores.

Results Higher femoral strains were significantly correlated with worse patient-reported functional outcomes. Femoral shear and transverse strains were positively correlated with six-month KOOS and WOMAC scores, after controlling for covariates. No relaxometry measures were correlated with patient-reported outcome scores. We identified the best-fit model for predicting WOMAC score using multiple MRI measures and patient-specific information, including sex, age, graft type, femoral transverse strain, femoral axial strain, and femoral shear strain. The best-fit model significantly predicted WOMAC score (p<0.001) better than any one individual MRI metric alone. When we regressed the model-predicted WOMAC scores against the patient-reported WOMAC scores, we found that our model achieved a goodness of fit exceeding 0.52.

Conclusions This work presents the first use of dualMRI in vivo in a cohort of participants at risk for developing osteoarthritis. Our results indicate that both shear and transverse strains are highly correlated with patient-reported outcome severity could serve as novel imaging biomarkers to predict the development of osteoarthritis.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study was funded by NIH 2 R01 AR063712.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

IRB of University of Colorado gave ethical approval for this work.

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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Data Availability

All data produced in the present study are available upon reasonable request to the authors.

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