ACL Size, but Not Signal Intensity, Is Influenced by Sex, Body Size, and Knee Anatomy

Samuel C Barnett, Martha M Murray, Sean W Flannery, BEAR Trial Team, Danilo Menghini, Braden C Fleming, Ata M Kiapour, Benedikt Proffen, Nicholas Sant, Gabriela Portilla, Ryan Sanborn, Christina Freiberger, Rachael Henderson, Kirsten Ecklund, Yi-Meng Yen, Dennis Kramer, Lyle Micheli, Samuel C Barnett, Martha M Murray, Sean W Flannery, BEAR Trial Team, Danilo Menghini, Braden C Fleming, Ata M Kiapour, Benedikt Proffen, Nicholas Sant, Gabriela Portilla, Ryan Sanborn, Christina Freiberger, Rachael Henderson, Kirsten Ecklund, Yi-Meng Yen, Dennis Kramer, Lyle Micheli

Abstract

Background: Little is known about sex-based differences in anterior cruciate ligament (ACL) tissue quality in vivo or the association of ACL size (ie, volume) and tissue quality (ie, normalized signal intensity on magnetic resonance imaging [MRI]) with knee anatomy.

Hypothesis: We hypothesized that (1) women have smaller ACLs and greater ACL normalized signal intensity compared with men, and (2) ACL size and normalized signal intensity are associated with age, activity levels, body mass index (BMI), bicondylar width, intercondylar notch width, and posterior slope of the lateral tibial plateau.

Study design: Cross-sectional study; Level of evidence, 3.

Methods: Knee MRI scans of 108 unique ACL-intact knees (19.7 ± 5.5 years, 62 women) were used to quantify the ACL signal intensity (normalized to cortical bone), ligament volume, mean cross-sectional area, and length. Independent t tests were used to compare the MRI-based ACL parameters between sexes. Univariate and multivariate linear regression analyses were used to investigate the associations between normalized signal intensity and size with age, activity levels, BMI, bicondylar width, notch width, and posterior slope of the lateral tibial plateau.

Results: Compared with men, women had significantly smaller mean ACL volume (men vs women: 2028 ± 472 vs 1591 ± 405 mm3), cross-sectional area (49.4 ± 9.6 vs 41.5 ± 8.6 mm2), and length (40.8 ± 2.8 vs 38.1 ± 3.1 mm) (P < .001 for all), even after adjusting for BMI and bicondylar width. There was no difference in MRI signal intensity between men and women (1.15 ± 0.24 vs 1.12 ± 0.24, respectively; P = .555). BMI, bicondylar width, and intercondylar notch width were independently associated with a larger ACL (R 2 > 0.16, P < .001). Younger age and steeper lateral tibial slope were independently associated with shorter ACL length (R 2 > 0.03, P < .04). The combination of BMI and bicondylar width was predictive of ACL volume and mean cross-sectional area (R 2 < 0.3). The combination of BMI, bicondylar width, and lateral tibial slope was predictive of ACL length (R 2 = 0.39). Neither quantified patient characteristics nor anatomic variables were associated with signal intensity.

Conclusion: Men had larger ACLs compared with women even after adjusting for BMI and knee size (bicondylar width). No sex difference was observed in signal intensity, suggesting no difference in tissue quality. The association of the intercondylar notch width and lateral tibial slope with ACL size suggests that the influence of these anatomic features on ACL injury risk may be partially explained by their effect on ACL size.

Registration: NCT02292004 and NCT02664545 (ClinicalTrials.gov identifier).

Keywords: ACL; anatomy; sex differences; signal intensity.

Conflict of interest statement

One or more of the authors has declared the following potential conflict of interest or source of funding: This study received funding support from the Translational Research Program at Boston Children’s Hospital, the Children’s Hospital Orthopaedic Surgery Foundation, the Children’s Hospital Sports Medicine Foundation, Boston Children’s Hospital Faculty Council, the Football Players Health Study at Harvard University (funded by a grant from the National Football League Players Association), and the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grants R01-AR065462 and R01-AR056834). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Medical School, Harvard University or its affiliated academic healthcare centers, the National Football League Players Association, Boston Children’s Hospital, or the National Institutes of Health. M.M.M. is a founder, paid consultant, and equity holder in Miach Orthopaedics, which was formed to work on upscaling production of the BEAR scaffold. M.M.M. has also received honoraria from the Musculoskeletal Transplant Foundation. B.C.F. is a paid associate editor for The American Journal of Sports Medicine and the spouse of M.M.M. with the inherently same conflicts. A.M.K. is a paid consultant for Miach Orthopaedics. D.K. and Y.-M.Y. have received education payments from Kairos Surgical. B.P. has manufactured the scaffolds used in the trials at Boston Children’s Hospital and is a paid consultant and equity holder in Miach Orthopaedics. N.S. has manufactured scaffolds used in the trials at Boston Children’s Hospital and is a paid consultant for Miach Orthopaedics. M.M.M., A.M.K., B.P., and N.S. maintained a conflict-of-interest management plan that was approved by Boston Children’s Hospital and Harvard Medical School during the conduct of the trial, with oversight by both conflict-of-interest committees and the institutional review board of Boston Children’s Hospital. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

© The Author(s) 2021.

Figures

Figure 1.
Figure 1.
(A) Three-dimensional segmentation of the anterior cruciate ligament (ACL) from magnetic resonance (MR) image stacks, and measurement techniques used to quantify (B) bicondylar and notch widths (BCW and NW) and (C) posterior slope of the lateral tibial plateau. The dashed red lines indicate the line passing through the inferior aspects of the femoral condyles (B) and the reference lines to measure the posterior slope of the lateral tibial plateau (C).
Figure 2.
Figure 2.
Representative images of the anterior cruciate ligament for a (A) female and a (B) male patient.
Figure 3.
Figure 3.
Sex-based differences in anterior cruciate ligament (ACL) size (volume, mean cross-sectional area, and length) and normalized signal intensity. Bars are median and P values are 2-sided.
Figure 4.
Figure 4.
Univariate regression analysis demonstrating the linear relationship of anterior cruciate ligament (ACL) size (volume, mean cross-sectional area [CSA], and length) and signal intensity with age. Red dots represent women and blue dots men. The regression line (solid line) and corresponding 95%CI (dashed lines) are shown for each univariate regression analysis.
Figure 5.
Figure 5.
Univariate regression analysis demonstrating the linear relationship of anterior cruciate ligament (ACL) size (volume, mean cross-sectional area [CSA], and length) and signal intensity with Marx Activity Score. Red dots represent women and blue dots men. The regression line (solid line) and corresponding 95%CI (dashed lines) are shown for each univariate regression analysis.
Figure 6.
Figure 6.
Univariate regression analysis demonstrating the linear relationship of anterior cruciate ligament (ACL) size (volume, mean cross-sectional area [CSA], and length) and signal intensity with body mass index (BMI). Red dots represent women and blue dots men. The regression line (solid line) and corresponding 95%CI (dashed lines) are shown for each univariate regression analysis.
Figure 7.
Figure 7.
Univariate regression analysis demonstrating the linear relationship of anterior cruciate ligament (ACL) size (volume, mean cross-sectional area [CSA], and length) and signal intensity with bicondylar width (BCW). Red dots represent women and blue dots men. The regression line (solid line) and corresponding 95%CI (dashed lines) are shown for each univariate regression analysis.
Figure 8.
Figure 8.
Univariate regression analysis demonstrating the linear relationship of anterior cruciate ligament (ACL) size (volume, mean cross-sectional area [CSA], and length) and signal intensity with intercondylar notch width (NW). Red dots represent women and blue dots men. The regression line (solid line) and corresponding 95%CI (dashed lines) are shown for each univariate regression analysis.
Figure 9.
Figure 9.
Univariate regression analysis demonstrating the inverse relationship of anterior cruciate ligament (ACL) size (volume, mean cross-sectional area [CSA], and length) and signal intensity with steeper lateral tibial slope (LTS). Red dots represent women and blue dots men. The regression line (solid line) and corresponding 95%CI (dashed lines) are shown for each univariate regression analysis.
Figure A1.
Figure A1.
Age distribution at the time of surgery for the included patients.

References

    1. Anderson AF, Dome DC, Gautam S, Awh MH, Rennirt GW. Correlation of anthropometric measurements, strength, anterior cruciate ligament size, and intercondylar notch characteristics to sex differences in anterior cruciate ligament tear rates. Am J Sports Med. 2001;29(1):58–66.
    1. Arendt E, Agel J, Dick R. Anterior cruciate ligament injury patterns among collegiate men and women. J Athl Train. 1999;34(2):86–92.
    1. Arendt E, Randall D. Knee injury patterns among men and women in collegiate basketball and soccer. AJSM. 1995;23(6):694–701.
    1. Beveridge JE, Machan JT, Walsh EG, et al. Magnetic resonance measurements of tissue quantity and quality using T2* relaxometry predict temporal changes in the biomechanical properties of the healing ACL. J Orthop Res. 2018;36(6):1701–1709.
    1. Beveridge JE, Proffen BL, Karamchedu NP, et al. Cartilage damage is related to ACL stiffness in a porcine model of ACL repair. J Orthop Res. 2019;37(10):2249–2257.
    1. Beveridge JE, Walsh EG, Murray MM, Fleming BC. Sensitivity of ACL volume and T2(*) relaxation time to magnetic resonance imaging scan conditions. J Biomech. 2017;56:117–121.
    1. Beynnon BD, Hall JS, Sturnick DR, et al. Increased slope of the lateral tibial plateau subchondral bone is associated with greater risk of noncontact ACL injury in females but not in males: a prospective cohort study with a nested, matched case-control analysis. Am J Sports Med. 2014;42(5):1039–1048.
    1. Biercevicz AM, Akelman MR, Fadale PD, et al. MRI volume and signal intensity of ACL graft predict clinical, functional, and patient-oriented outcome measures after ACL reconstruction. Am J Sports Med. 2015;43(3):693–699.
    1. Biercevicz AM, Miranda DL, Machan JT, Murray MM, Fleming BC. In situ, noninvasive, T2*-weighted MRI-derived parameters predict ex vivo structural properties of an anterior cruciate ligament reconstruction or bioenhanced primary repair in a porcine model. Am J Sports Med. 2013;41(3):560–566.
    1. Biercevicz AM, Murray MM, Walsh EG, et al. T2* MR relaxometry and ligament volume are associated with the structural properties of the healing ACL. J Orthop Res. 2014;32(4):492–499.
    1. Biercevicz AM, Proffen BL, Murray MM, Walsh EG, Fleming BC. T2* relaxometry and volume predict semi-quantitative histological scoring of an ACL bridge-enhanced primary repair in a porcine model. J Orthop Res. 2015;33(8):1180–1187.
    1. Cameron KL, Peck KY, Thompson BS, et al. Reference values for the Marx Activity Rating Scale in a young athletic population: history of knee ligament injury is associated with higher scores. Sports Health. 2015;7(5):403–408.
    1. Chandrashekar N, Slauterbeck J, Hashemi J. Sex-based differences in the anthropometric characteristics of the anterior cruciate ligament and its relation to intercondylar notch geometry: a cadaveric study. Am J Sports Med. 2005;33(10):1492–1498.
    1. Charlton WPH, St John TA, Ciccotti MG, Harrison N, Schweitzer M. Differences in femoral notch anatomy between men and women: a magnetic resonance imaging study. Am J Sports Med. 2002;30:329–333.
    1. Chaudhari AM, Zelman EA, Flanigan DC, Kaeding CC, Nagaraja HN. Anterior cruciate ligament-injured subjects have smaller anterior cruciate ligaments than matched controls: a magnetic resonance imaging study. Am J Sports Med. 2009;37(7):1282–1287.
    1. Christensen JJ, Krych AJ, Engasser WM, et al. Lateral tibial posterior slope is increased in patients with early graft failure after anterior cruciate ligament reconstruction. Am J Sports Med. 2015;43(10):2510–2514.
    1. Davis TJ, Shelbourne KD, Klootwyk TE. Correlation of the intercondylar notch width of the femur to the width of the anterior and posterior cruciate ligaments. Knee Surg Sports Traumatol Arthrosc. 1999;7(4):209–214.
    1. Dienst M, Schneider G, Altmeyer K, et al. Correlation of intercondylar notch cross sections to the ACL size: a high resolution MR tomographic in vivo analysis. Arch Orthop Trauma Surg. 2007;127(4):253–260.
    1. Eliasziw M, Young SL, Woodbury MG, Fryday-Field K. Statistical methodology for the concurrent assessment of interrater and intrarater reliability: using goniometric measurements as an example. Phys Ther. 1994;74(8):777–788.
    1. Fayad LM, Rosenthal EH, Morrison WB, Carrino JA. Anterior cruciate ligament volume: analysis of gender differences. J Magn Reson Imaging. 2008;27(1):218–223.
    1. Fleming BC, Vajapeyam S, Connolly SA, Magarian EM, Murray MM. The use of magnetic resonance imaging to predict ACL graft structural properties. J Biomech. 2011;44(16):2843–2846.
    1. Grassi A, Bailey JR, Signorelli C, et al. Magnetic resonance imaging after anterior cruciate ligament reconstruction: a practical guide. World J Orthop. 2016;7(10):638–649.
    1. Grassi A, Macchiarola L, Urrizola Barrientos F, et al. Steep posterior tibial slope, anterior tibial subluxation, deep posterior lateral femoral condyle, and meniscal deficiency are common findings in multiple anterior cruciate ligament failures: an MRI case-control study. Am J Sports Med. 2019;47(2):285–295.
    1. Gwinn DE, Wilckens JH, McDevitt ER, Ross G, Kao T. The relative incidence of anterior cruciate ligament injury in men and women at the United States Naval Academy. Am J Sports Med. 2000;28(1):98–102.
    1. Hashemi J, Chandrashekar N, Gill B, et al. The geometry of the tibial plateau and its influence on the biomechanics of the tibiofemoral joint. J Bone Joint Surg Am. 2008;90(12):2724–2734.
    1. Hashemi J, Chandrashekar N, Mansouri H, et al. Shallow medial tibial plateau and steep medial and lateral tibial slopes: new risk factors for anterior cruciate ligament injuries. Am J Sports Med. 2010;38(1):54–62.
    1. Hashemi J, Chandrashekar N, Mansouri H, Slauterbeck JR, Hardy DM. The human anterior cruciate ligament: sex differences in ultrastructure and correlation with biomechanical properties. J Orthop Res. 2008;26(7):945–950.
    1. Hashemi J, Mansouri H, Chandrashekar N, et al. Age, sex, body anthropometry, and ACL size predict the structural properties of the human anterior cruciate ligament. J Orthop Res. 2011;29(7):993–1001.
    1. Hewett TE, Myer GD, Ford KR. Anterior cruciate ligament injuries in female athletes: Part 1, mechanisms and risk factors. Am J Sports Med. 2006;34(2):299–311.
    1. Hosseinzadeh S, Kiapour AM. Age-related changes in ACL morphology during skeletal growth and maturation are different between females and males. J Orthop Res. 2021;39(4):841–849.
    1. Howell SM, Barad SJ. Knee extension and its relationship to the slope of the intercondylar roof. Implications for positioning the tibial tunnel in anterior cruciate ligament reconstructions. Am J Sports Med. 1995;23:288–294.
    1. Hudek R, Schmutz S, Regenfelder F, Fuchs B, Koch PP. Novel measurement technique of the tibial slope on conventional MRI. Clin Orthop Relat Res. 2009;467(8):2066–2072.
    1. Jamison ST, Flanigan DC, Nagaraja HN, Chaudhari AM. Side-to-side differences in anterior cruciate ligament volume in healthy control subjects. J Biomech. 2010;43(3):576–578.
    1. Kiapour AM, Ecklund K, Murray MM, et al. Changes in cross-sectional area and signal intensity of healing anterior cruciate ligaments and grafts in the first 2 years after surgery. Am J Sports Med. 2019;47(8):1831–1843.
    1. Kiapour AM, Yang DS, Badger GJ, et al. Anatomic features of the tibial plateau predict outcomes of ACL reconstruction within 7 years after surgery. Am J Sports Med. 2019;47(2):303–311.
    1. Komatsuda T, Sugita T, Sano H, et al. Does estrogen alter the mechanical properties of the anterior cruciate ligament? An experimental study in rabbits. Acta Orthop. 2006;77(6):973–980.
    1. Levins JG, Sturnick DR, Argentieri EC, et al. Geometric risk factors associated with noncontact anterior cruciate ligament graft rupture. Am J Sports Med. 2016;44(10):2537–2545.
    1. Li H, Chen S, Tao H, Li H, Chen S. Correlation analysis of potential factors influencing graft maturity after anterior cruciate ligament reconstruction. Orthop J Sports Med. 2014;2(10):2325967114553552.
    1. Li H, Tao H, Cho S, et al. Difference in graft maturity of the reconstructed anterior cruciate ligament 2 years postoperatively: a comparison between autografts and allografts in young men using clinical and 3.0-T magnetic resonance imaging evaluation. Am J Sports Med. 2012;40(7):1519–1526.
    1. Li H, Zeng C, Wang Y, et al. Association between magnetic resonance imaging-measured intercondylar notch dimensions and anterior cruciate ligament injury: a meta-analysis. Arthroscopy. 2018;34(3):889–900.
    1. Li Y, Hong L, Feng H, et al. Posterior tibial slope influences static anterior tibial translation in anterior cruciate ligament reconstruction: a minimum 2-year follow-up study. Am J Sports Med. 2014;42(4):927–933.
    1. Lipps DB, Wilson AM, Ashton-Miller JA, Wojtys EM. Evaluation of different methods for measuring lateral tibial slope using magnetic resonance imaging. Am J Sports Med. 2012;40(12):2731–2736.
    1. Murray MM, Fleming BC, Badger GJ, et al. Bridge-enhanced anterior cruciate ligament repair is not inferior to autograft anterior cruciate ligament reconstruction at 2 years: results of a prospective randomized clinical trial. Am J Sports Med. 2020;48(6):1305–1315.
    1. Murray MM, Kalish LA, Fleming BC, et al. Bridge-enhanced anterior cruciate ligament repair: two-year results of a first-in-human study. Orthop J Sports Med. 2019;7(3):232596711882435.
    1. Murray MM, Kiapour AM, Kalish LA, et al. Predictors of healing ligament size and magnetic resonance signal intensity at 6 months after bridge-enhanced anterior cruciate ligament repair. Am J Sports Med. 2019;47(6):1361–1369.
    1. Napier RJ, Garcia E, Devitt BM, Feller JA, Webster KE. Increased radiographic posterior tibial slope is associated with subsequent injury following revision anterior cruciate ligament reconstruction. Orthop J Sports Med. 2019;7(11):2325967119879373.
    1. Park JS, Nam DC, Kim DH, Kim HK, Hwang SC. Measurement of knee morphometrics using MRI: a comparative study between ACL-injured and non-injured knees. Knee Surg Relat Res. 2012;24(3):180–185.
    1. Postma WF, West RV. Anterior cruciate ligament injury-prevention programs. J Bone Joint Surg Am. 2013;95(7):661–669.
    1. Proffen BL, Fleming BC, Murray MM. Histologic predictors of maximum failure loads differ between the healing ACL and ACL grafts after 6 and 12 months in vivo. Orthop J Sports Med. 2013;1(6):2325967113512457.
    1. Rose M, Crawford D. Allograft maturation after reconstruction of the anterior cruciate ligament is dependent on graft parameters in the sagittal plane. Orthop J Sports Med. 2017;5(8):2325967117719695.
    1. Saito M, Nakajima A, Sonobe M, et al. Superior graft maturation after anatomical double-bundle anterior cruciate ligament reconstruction using the transtibial drilling technique compared to the transportal technique. Knee Surg Sports Traumatol Arthrosc. 2019;27(8):2468–2477.
    1. Salmon LJ Heath E Akrawi H, et al. 20-year outcomes of anterior cruciate ligament reconstruction with hamstring tendon autograft: the catastrophic effect of age and posterior tibial slope. Am J Sports Med. 2018;46(3):531–543.
    1. Shelbourne KD, Davis TJ, Klootwyk TE. The relationship between intercondylar notch width of the femur and the incidence of anterior cruciate ligament tears. A prospective study. Am J Sports Med. 1998;26(3):402–408.
    1. Shelbourne KD, Facibene WA, Hunt JJ. Radiographic and intraoperative intercondylar notch width measurements in men and women with unilateral and bilateral anterior cruciate ligament tears. Knee Surg Sports Traumatol Arthrosc. 1997;5(4):229–233.
    1. Slauterbeck J, Clevenger C, Lundberg W, Burchfield DM. Estrogen level alters the failure load of the rabbit anterior cruciate ligament. J Orthop Res. 1999;17(3):405–408.
    1. Tanaka Y, Yonetani Y, Shiozaki Y, et al. MRI analysis of single-, double-, and triple-bundle anterior cruciate ligament grafts. Knee Surg Sports Traumatol Arthrosc. 2014;22(7):1541–1548.
    1. Van Dyck P, Zazulia K, Smekens C, et al. Assessment of anterior cruciate ligament graft maturity with conventional magnetic resonance imaging: a systematic literature review. Orthop J Sports Med. 2019;7(6):2325967119849012.
    1. Watanabe BM, Howell SM. Arthroscopic findings associated with roof impingement of an anterior cruciate ligament graft. Am J Sports Med. 1995;23:616–625.
    1. Webb JM, Salmon LJ, Leclerc E, Pinczewski LA, Roe JP. Posterior tibial slope and further anterior cruciate ligament injuries in the anterior cruciate ligament-reconstructed patient. Am J Sports Med. 2013;41(12):2800–2804.
    1. Weiler A, Peters G, Mäurer J, Unterhauser FN, Südkamp NP. Biomechanical properties and vascularity of an anterior cruciate ligament graft can be predicted by contrast-enhanced magnetic resonance imaging. A two-year study in sheep. Am J Sports Med. 2001;29(6):751–761.
    1. Whitney DC, Sturnick DR, Vacek PM, et al. Relationship between the risk of suffering a first-time noncontact ACL injury and geometry of the femoral notch and ACL: a prospective cohort study with a nested case-control analysis. Am J Sports Med. 2014;42(8):1796–1805.

Source: PubMed

3
구독하다