Summary

Investigating the association between MRI findings following anterior cruciate ligament (ACL) injury and synovial fluid biomarker profile at the time of surgery.

Abstract

Purpose

To Investigate the association between MRI findings following anterior cruciate ligament (ACL) injury and synovial fluid biomarker profile at the time of surgery.

Methods

Patients undergoing surgery for ACL injury from October 2011 to December 2021 were included in a database of subjects who had synovial fluid samples collected at the time of surgery. From this cohort, 82 subjects with acute ACL injury were retrospectively selected who met the following inclusion criteria: no history of prior knee trauma to suggest chronic ACL injury, history of acute non-contact knee injury, MRI examination of the knee performed within 3 weeks of knee injury, subsequent knee surgery performed between 4 and 12 weeks of knee injury, and no additional ligament tear requiring surgical treatment. All subjects underwent a preoperative MRI examination of the knee using multi-planar, multi-contrast fast spin-echo sequences. Synovial fluid was aspirated from the operative knee prior to surgical incision. Concentrations of inflammatory biomarkers including regulation on activation normal T cell expressed and secreted (RANTES), interleukin 6 (IL-6), vascular endothelial growth factor (VEGF), tissue inhibitor matrix metalloproteinase 1 (TIMP1), interleukin 1 receptor agonist (IL1-RA) and matrix metalloproteinase 3 (MMP-3) were measured. The MRI examinations of all subjects were reviewed by a fellowship trained musculoskeletal radiologist to assess the presence and severity of various MRI features of acute and chronic knee injury using the validated Anterior Cruciate Ligament Osteoarthritis Score (ACLOAS) system. Nonparametric Wilcoxon tests and Fisher’s exact test were used to compare demographic factors, MRI findings, clinical symptoms, and synovial fluid inflammatory biomarkers between clusters. K-means cluster analysis was used to identify 2 distinct clusters of subjects with acute ACL injury based on biomarkers concentrations in synovial fluid.

Results

The mean age of the cohort was 31.6 ± 8 years, average body mass index (BMI) was 25.5 ± 4.4 kg/m2. There 42.7% (n=35) of the cohort was female and 85.4% (n=70) were non-smokers. Two distinct clusters were identified: cluster 1 included 45 subjects and was marked by older subjects (33.2 ± 9.1 years, p=.038) with lower levels of all inflammatory synovial fluid biomarkers. Cluster 2 included 37 subjects and was marked by younger patients (29.7 ± 6.1 years, p=.038) with a more pro-inflammatory synovial fluid biomarker profile, higher ACLOAS Hoffa’s synovitis score (p=.001), and a higher incidence of subchondral bone fractures (54%, p=.002). There were no differences between clusters in time from injury to surgery (p=), BMI (p=.141), or ACLOAS meniscus (p=.086), cartilage (p=.730), or effusion scores (p=.202).

Conclusion

Given the variable outcomes seen following ACL reconstruction (ACLR) surgery, a better understanding of the pathophysiology following ACL injury is needed. This study found distinct cluster of patients who exhibited a higher inflammatory reaction at the time of surgery as well as more severe findings on preoperative MRI. These findings could be used to identified clinical parameters associated with more inflammation at the time of surgery and their effect on clinical outcomes of ACLR.