Anterior cruciate ligament autograft maturation on sequential postoperative MRI is not correlated with clinical outcome and anterior knee stability

Lutz, Patricia M.; Achtnich, Andrea; Schütte, Vincent; Woertler, Klaus; Imhoff, Andreas B.; Willinger, Lukas

doi:10.1007/s00167-021-06777-4

Anterior cruciate ligament autograft maturation on sequential postoperative MRI is not correlated with clinical outcome and anterior knee stability

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Published: 05 November 2021

Volume 30, pages 3258–3267, (2022)
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Knee Surgery, Sports Traumatology, Arthroscopy Aims and scope

Anterior cruciate ligament autograft maturation on sequential postoperative MRI is not correlated with clinical outcome and anterior knee stability

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Patricia M. Lutz¹,
Andrea Achtnich¹^na1,
Vincent Schütte²,
Klaus Woertler³,
Andreas B. Imhoff ORCID: orcid.org/0000-0001-5085-6446¹ &
…
Lukas Willinger¹

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Abstract

Purpose

Magnetic resonance imaging (MRI) signal intensity is correlated to structural postoperative changes of the anterior cruciate ligament (ACL) autograft. The purpose of this study was to investigate the ACL autograft maturation process via MRI over 2 years postoperatively, compare it to a native ACL signal and correlate the results with clinical outcome, return to preinjury sports levels, and knee laxity measurements.

Methods

ACL autograft signal intensity was measured in 17 male patients (age, 28.3 ± 7.0 years) who underwent ACL reconstruction with hamstring autograft at 6 weeks, 3-, 6-, 12-, and 24 months postoperatively by 3 Tesla MRI. Controls with an intact ACL served as control group (22 males, 8 females; age, 26.7 ± 6.8 years). An ACL/PCL ratio (APR) and ACL/muscle ratio (AMR) was calculated to normalize signals to soft tissue signal. APR and AMR were compared across time and to native ACL signal. Clinical outcome scores (IKDC, Lysholm), return to preinjury sports levels (Tegner activity scale), and knee laxity measurement (KT-1000) were obtained and correlated to APR and AMR at the respective time points.

Results

The APR and AMR of the ACL graft changed significantly from the lowest values at 6 weeks to reach the highest intensity after 6 months (p < 0.001). Then, the APR and AMR were significantly different from a native ACL 6 months after surgery (p < 0.01) but approached the APR and AMR of the native ACL at 1- and 2 years after surgery (p < 0.05). The APR changed significantly during the first 2 years postoperatively in the proximal (p < 0.001), mid-substance (p < 0.001), and distal (p < 0.01) intraarticular portion of the ACL autograft. A hypo-intense ACL MRI signal was associated with return to the preinjury sports level (p < 0.05). No correlation was found between ACL MRI graft signal and clinical outcome scores or KT-1000 measurements.

Conclusion

ACL grafts undergo a continuous maturation process in the first 2 years after surgery. The ACL graft signals became hyper-intense 6 months postoperatively and approximated the signal of a native intact ACL at 12- and 24 months. Patients with a hypo-intense ACL graft signal at 2 years follow-up were more likely to return to preinjury sports levels. The results of the present study provide a template for monitoring the normal ACL maturation process via MRI in case of prolonged clinical symptoms. However, subjective outcome and clinical examination of knee laxity remain important to assess the treatment success and to allow to return to sports.

Level of evidence

III.

Anterior cruciate ligament grafts display differential maturation patterns on magnetic resonance imaging following reconstruction: a systematic review

Article 13 September 2019

Hamstring tendon autografts do not show complete graft maturity 6 months postoperatively after anterior cruciate ligament reconstruction

Article Open access 14 July 2018

Sufficient MRI graft structural integrity at 9 months after anterior cruciate ligament reconstruction with hamstring tendon autograft

Article 18 January 2022

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Introduction

Anterior cruciate ligament (ACL) reconstruction aims to restore knee stability and regain normal knee function. This allows safe return to activity and reduce the risk of re-injuries. Despite advances in surgical techniques, early ACL re-tears are still a major concern [30, 32, 37]. One reason for early re-ruptures is biological failure due to the remodelling process [29]. The graft maturation process (also known as ligamentization) during the early postoperative phase negatively affects the biomechanical properties of the graft [36, 41, 46]. The decrease of mechanical strength during the first period is of clinical importance as it puts the graft at risk of not meeting its demands [2, 18, 21, 23, 40, 46, 47]. Hence, assessing ACL graft maturity before returning to sports is of high clinical interest and magnetic resonance imaging (MRI) has been shown to be a feasible option [11, 12]. Animal models showed that MRI signal intensity is significantly correlated to structural properties of the ACL graft [5, 46]. A high signal intensity on MRI has been linked to decreased mechanical properties such as low load to failure [46]. In recent years, several MRI studies showed that signal intensity changes of the ACL graft are correlated with the progress of graft maturation in human patients [9, 11, 27, 43]. ACL graft MRI signal intensity increases during the first 6 months followed by a subsequent decline [Full size image

The proximal ACL graft underwent a significant MRI signal change from 6 weeks to 6 months after surgery and showed the highest signal intensity at this time point (p < 0.001). The APR subsequently declined to approximate the APR of a native proximal ACL at 1 and 2 years. The proximal APR was significantly lower than a native ACL at 6 weeks (p < 0.001) and higher at 6 months (p < 0.05) after surgery.

Similarly, the APR of the mid-substance ACL graft ran through a significant transformation from 6 weeks to 2 years postoperatively. While the APR 6 months after ACL-R is significantly different from a native mid-substance ACL (p < 0.01), the APR after 1 and 2 years showed a similar MRI signal compared with a native ACL.

APR of the distal section of the ACL graft showed a significant rise within the first 6 months postoperatively (p < 0.05) before drop** gradually at 1 and 2 years. The APR of distal section of the ACL autograft was significantly lower than the native ACL at all time points except from 6 months postoperatively (all p < 0.01).

AMR measurements

The AMR of the ACL autograft over the postoperative period is shown in Fig. 2B. The AMR changed significantly at the proximal (p < 0.001), mid-substance (p < 0.001), and distal (p < 0.05) part of the ACL graft.

AMR of the proximal ACL portion rose significantly from 6 weeks to 6 months (p < 0.001) after surgery and was by then significantly different to a native ACL (p < 0.001). Subsequently, the AMR started to decline to reach a similar AMR of the native proximal ACL at 1 and 2 years.

The mid-substance AMR increased significantly from 6 weeks to 6 months postoperatively (p < 0.001) before decreasing at 1 year and 2 years postoperatively (p < 0.01). The AMR was significant higher at 3- and 6 months after ACL-R compared with a native ACL (p < 0.001) but was not different from a native mid-substance ACL at 1 and 2 years.

The distal AMR rose significantly between 6 weeks and 6 months postoperatively (p < 0.05). It then dropped slowly to the lowest AMR at 2 years postoperatively. AMR of the distal intraarticular graft section was significantly lower than a native ACL at 2 years after surgery (p < 0.05, Fig. 3).

Correlation to clinical outcome, knee stability, and return to sports

Anterior knee laxity measured by KT-1000 device was 1.9 ± 1.7 mm and 2.4 ± 2.3 mm higher compared to the healthy contralateral knee at 1 and 2 years postoperatively, respectively. For neither APR nor AMR a significant correlation with KT-1000 measurements at the respective time points could be identified.

IKDC and Lysholm score improved significantly from preoperative values to postoperative values at 6 months, 1-, and 2 years postoperatively (all p < 0.001, Fig. 4). There was also a significant increase in clinical outcome scores between 6 months and 1 year postoperatively but not from 1 to 2 years (IKDC: p < 0.001, Lysholm score p < 0.05). APR and AMR were not associated with IKDC and Lysholm score at any time point.

Return to preinjury sports levels

94% (16/17) of the patients returned to sports within 2 years after ACL-R. One patient suffered a contralateral ACL injury 1.5 years after initial ACL-R and could therefore not RTS at final follow-up. Median TAS was 6 (range 4–9) before injury, 4 (range 3–6) after 6 months, 5 (range 1–7) after 1 year and 6 (range 1–9) at final follow up. At 1 year and 2 years follow-up, 41% (7/17 patients) and 65% (11/17) achieved the preinjury TAS level, respectively. TAS was not correlated with APR or AMR at any time point within the small patients’ cohort. However, APR and AMR of the ACL mid-substance were significantly lower (hypo-intense) in patients who could return to the preinjury sports level compared to those who did not achieve the same sports level (p < 0.05).

Discussion

The most important findings of our study were that an ACL autograft is undergoing a significant transformation process during the first 2 years postoperatively which is consistent with the previously described ligamentization process [9, 20, 45]. These findings confirmed our first hypothesis that an ACL graft exhibits a high MRI signal intensity 6 months after surgery but approximates the MRI appearance of a native ACL at 1- and 2 years postoperatively. Hypointense MRI signal (lower APR or AMR) did not correlate with higher clinical outcome scores and lower anterior knee laxity what contradicted our second hypothesis. However, patients with lower mid-substance ACL signal intensity were more likely to return to the preinjury sports level.

It is known that T2 relaxation time is correlated to tissue water content and collagen orientation, with higher values indicating greater disorganization and lower values representing less disorganization [5, 9]. After ACL-R, values are expected to increase due to graft remodelling followed by a subsequent reduction [3, 9, 16, 24, 45]. In the present study, the graft signal intensity on MRI was normalized to the subject-specific signal intensity of both the PCL and the gastrocnemius muscle in order to minimize inter-scan variability. Muscle tissue was chosen as a second internal reference to avoid systematic measurement error caused by variation due to possible degenerative changes of the PCL. It was concluded that not including the measurement of background noise (proton density of extracorporeal hydrogen atoms) the reliability and accuracy was increased. This assumption is based on the experience of the two readers, which showed highly variable background noise between subjects and the location of ROI.

ACL grafts underlie a histological healing process that includes initial avascular necrosis, revascularization, resynovialization, and remodelling [2, 10, 14, 29, 47]. Previous research revealed that the revascularization process influences the ACL graft signal intensity in MRI with signal intensity being significantly associated with time from surgery [18, 25, 27, 38]. In line with previous reports, the graft signal intensity in the present study peaks at 6 months, followed by a constant decrease [9, 20, 45]. In agreement with the results of Chu and Williams [9], the present study suggests an approximation of ACL graft signal intensity to the MRI signal of a native ACL 1- and 2 years postoperatively indicating graft maturity.

More specifically, the native ACL and the ACL autografts demonstrated regional differences in MRI signal intensity. It was observed that distal regions of native ACL exhibited higher APR and AMR (hyper-intense signal) compared to proximal or mid-substance regions (Fig. 3F). In contrast, the distal ACL autograft showed lower APR and AMR (hypo-intense signal) compared to the mid-substance in the early healing phase and this phenomenon was also observed in former studies [20, 21, 38, 45]. Tashiro et al. found higher MRI signal in the proximal and mid-substance part of the ACL graft compared to the distal graft at 6 months postoperatively [38]. The authors assumed that a high graft bending angle at the femoral drill hole contributes to increased graft signals due to elevated tension after footstrike [38]. Ma et al. [21] found also the highest MRI signal in the proximal ACL graft and thought that graft length change patterns during flexion, femoral fixation method, and the angle of the femoral tunnel are contributing factors for a longer maturation process proximally. The proximal and mid-substance section of the ACL autograft seems to exhibit a higher collagen disorganization in the remodelling phase compared to the distal part [20, 21, 38], and is, hence, presumably more vulnerable for re-injury.

To avoid early biological failures, some studies tried to find correlations between MRI findings and functional and clinical outcomes lately. In previous reports, MRI- and KT-1000 measurements after ACL-R were either poorly or not correlated [11, 12]. In agreement with the results of Hakozaki et al. [11], no significant correlation between APR or AMR and KT-1000 measurements was identified after 12 or 24 months in the present study. These findings emphasize the importance of a clinical laxity assessment to ensure knee stability before allowing the patient return to sports.

Furthermore, no correlation between APR/AMR and clinical scores could be found in the present study. These results are further strengthened by a study of Li et al. [17], who were not able to show a significant association between ACL autograft SNQ and IKDC, Lysholm score, and TAS. Most patients (94%) of the present study were able to return to sports and 65% of these recreational athletes were able to achieve the same sports level. Interestingly, lower APR/AMR of the ACL mid-substance part increased the chance of returning to the same preinjury sports level 2 years after surgery. This finding is supported by the results of Li et al. [18], who were able to show a significant positive association between TAS and SNQ values in male subjects.

This study has several limitations. Firstly, histologic data are missing. Therefore, the transformation process of a reconstructed ACL in the first 2 years postoperatively was only described on the basis of MRI examinations. Secondly, only males were included in the ACL-R group so the results cannot be transferred for ACL ligamentization in females. Thirdly, even though the number of patients in this study was low, the statistical power of the current study was 0.87. Considering six MRI scans per patient, the number of subjects was intended to be narrowly restricted to minimize the number of scans and costs. Lastly, the measurement methods (APR, AMR) used in this study have not been used before. Nevertheless, the authors believe that by using two different ratios and by not including background noise measurements the drawback was overcome.

The results of the present study provide a template for monitoring the normal ACL maturation process via MRI in case of prolonged clinical symptoms. However, subjective outcome and clinical examination of knee laxity remain important to assess the treatment success and to allow to return to sports.

Conclusion

ACL grafts undergo a continuous maturation process in the first 2 years after surgery. The ACL graft signals became hyper-intense 6 months postoperatively and approximate the signal of a native intact ACL at 12- and 24 months. ACL autograft signal intensity exhibits significant differences between the mid-substance and distal portion in the early healing phase. Patients with a hypo-intense ACL graft signal at 2 years follow-up were more likely to return to the preoperative sports level.

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Patricia M. Lutz and Andrea Achtnich have contributed equally to this work.

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Department for Orthopedic Sports Medicine, Technical University Munich, Ismaninger Strasse 22, 81675, Munich, Germany
Patricia M. Lutz, Andrea Achtnich, Andreas B. Imhoff & Lukas Willinger
Department for Orthopedic and Trauma Surgery, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Strasse 40, 06120, Halle (Saale), Germany
Vincent Schütte
Department of Diagnostic and Interventional Radiology, Technical University of Munich, Ismaninger Strasse 22, 81675, Munich, Germany
Klaus Woertler

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Patricia M. Lutz
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Contributions

All listed authors have contributed substantially to this work (PML, LW, KW, and AA for the study conception and design; PML, LW, and VS for the data collection; LW and PML for the data analysis; LW, PML, KW, and ABI for the data interpretation; PML, LW, and AA for the drafting of the manuscript, the figures, and the literature research; PML, AA, VS, KW, ABI, and LW for critical revising the manuscript in terms of intellectual and professional input) and have approved the submission to Knee Surgery, Sports Traumatology, Arthroscopy (KSSTA).

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Correspondence to Andreas B. Imhoff.

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Andreas B. Imhoff is a consultant for Arthrosurface and Medi Bayreuth and receives royalties from Arthrex and Arthrosurface. All other authors declare that they have no conflict of interest related to this study.

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Ethical approval was obtained from the Ethics Committee of the Technical University Munich (329/19S). All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Lutz, P.M., Achtnich, A., Schütte, V. et al. Anterior cruciate ligament autograft maturation on sequential postoperative MRI is not correlated with clinical outcome and anterior knee stability. Knee Surg Sports Traumatol Arthrosc 30, 3258–3267 (2022). https://doi.org/10.1007/s00167-021-06777-4

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Received: 14 May 2021
Accepted: 18 October 2021
Published: 05 November 2021
Issue Date: October 2022
DOI: https://doi.org/10.1007/s00167-021-06777-4

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Anterior cruciate ligament autograft maturation on sequential postoperative MRI is not correlated with clinical outcome and anterior knee stability