Race and Gender Differences in Anterior Cruciate Ligament Femoral Footprint Location and Orientation: A 3D‐MRI Study

Objective The femoral tunnel position is crucial to anatomic single‐bundle anterior cruciate ligament (ACL) reconstruction, but the ideal femoral footprint position are mostly based on small‐sized cadaveric studies and elderly patients with a single ethnic background. This study aimed to identify potential race‐ or gender‐specific differences in the ACL femoral footprint location and ACL orientation, determine the correlation between the ACL orientation and the femoral footprint location. Methods Magnetic resonance images (MRIs) of 90 Caucasian participants and 90 matched Chinese subjects were used for reconstruction of three‐dimensional (3D) femur and tibial models. ACL footprints were sketched by several experienced orthopedic surgeons on the MRI photographs. The anatomical coordinate system was applied to reflect the ACL footprint location and orientation of scanned samples. The femoral ACL footprint locations were represented by their distance from the origin in the anteroposterior (A/P) and distal‐proximal (D/P) directions. The orientation of the ACL was described with the sagittal, coronal and transverse deviation angles. The ACL orientation and femoral footprint position were compared by the two‐sided t‐test. Multiple regression analysis was used to study the correlation between the orientation and femoral footprint position. Results The average femur footprint A/P position was −6.6 ± 1.6 mm in the Chinese group and −5.1 ± 2.3 mm in the Caucasian group, (p < 0.001). The average femur footprint D/P position was −2.8 ± 2.4 mm in Chinese and − 3.9 ± 2.0 mm in Caucasians, (p = 0.001). The Chinese group had a mean difference of a 1.5 mm (6.1%) more posterior and 1.1 mm (5.3%) more proximal in the position from the flexion‐extension axis (FEA). And the males have a sagittal plane elevation about 4–5° higher than females in both racial groups. Furthermore, for every 1% (0.40 mm) increase in A/P and D/P values, the sagittal angle decreased by about 0.12° and 0.24°, respectively; the coronal angle decreased by about 0.10° and 0.30°, respectively. For every 1% (0.40 mm) increase in D/P value, the transverse angle increased by about 0.14°. Conclusion The significant race‐ and gender‐specific differences in the femoral footprint and orientation of the ACL should be taken in consideration during anatomic single‐bundle ACL reconstruction. Furthermore, the quantitative relationship between the ACL orientation and the footprint location might provide some reference for surgeons to develop a surgical strategy in ACL single‐bundle reconstruction and revision.


Introduction
2][3][4] As more adolescents participate in high-level sports and older adults remain active for longer periods of time, the incidence of ACL injury and reconstruction may be higher than previously reported. 1][7][8] The main concept of anatomic ACL reconstruction is to structurally and functionally restore the native ACL attachment, and thereby achieving better clinical results than non-anatomic ACL reconstruction. 9,10Accurate tunnel placement requires an excellent knowledge of the ACL footprint.2][13] And potential differences in the femoral ACL footprint location and orientation between different races and genders have not been identified in the previous studies.Furthermore, perfect anatomical reconstruction usually does not result in intercondylar notch impingement in the extension position of the knee, 14,16 however, it was still reported that the position of the femoral tunnel in a considerable number of patients had different degrees of deviation from the anatomical center of the femoral footprint (especially in the cases of ACL revision and chronic ACL injury). 17,19This may lead to intercondylar impingement and thus rupture of the graft.Therefore, analyzing the quantitative relationship between the ACL femoral footprint position and the ACL direction might help the surgeon to adjust the internal opening position of the femoral tunnel according to the intraoperative X-ray images, quantitatively change the direction of the graft, and thus provide a certain auxiliary reference for avoiding the intercondylar notch impingement.
1][22][23][24][25] Therefore, we speculated that the ACL femoral footprint in Chinese would differ significantly from that in Caucasians.Thus, the purposes of the present study were: (i) to explore the three-dimensional, morphological differences in the femoral ACL footprint and ACL orientation between Chinese and Caucasian individuals with intact ACLs; and (ii) to determine the correlation between the ACL orientation and location of the femoral ACL footprint.

Patient Selection and Study Design
Medical records and magnetic resonance imaging (MRI) databases were reviewed after obtaining informed consent from all the patients and the ethics committee of Chinese PLA Southern Theater Command General Hospital [IRB  2019 No.10].We also established a unified set of MRI protocols with our partner units (Department of Orthopedics, University Hospital Balgrist, Zurich, Switzerland) (Ethics Committee Northeast and Central Switzerland 2018-01410).Inclusion criteria included patients aged less than 45 years of age who had no diagnosed knee problems.A retrospective analysis of 647 Caucasian patients from January 2015 to December 2017 and 732 ACL-intact Chinese from October 2019 to December 2022 was performed.Our patient information database clearly records the age, gender, height, weight and body mass index (BMI) of all the patients.When we compared the above information for all patients, we found that 93 Caucasians (60 males and 33 females) and 102 Chinese (72 males and 30 females) people matched each other (60 vs. 72 males, 33 vs. 30 females).In order to pair the patients, after randomized elimination of 12 Chinese males and three Caucasian females, a cohort of 60 men and 30 women was formed (Table 1) (all p > 0.05).A review of MRI images was performed by three senior orthopedists (Li, Chen, and Shen) to screen for associated injuries.Exclusion criteria included meniscus tears, significant knee joint degeneration, and the inability of MRI images to be used to identify or reconstruct ACL footprints due to poor quality.

Magnetic Resonance Parameters and Protocols
Three-dimensional (3D) MRI, a method that has been proven to have strong agreement with open cadaveric dissection (considered the gold standard), and can be used interchangeably. 26,27All enrolled subjects were scanned by a 3.0-T MRI system with fully extended knees.Proton density 3D fast spin-echo volume sequences (Skyra; Siemens, Guangzhou, China) were applied to collect Chinese images (slice thickness: 0.50 mm, voxel size: 0.3 Â 0.3 Â 0.5 mm) (Figure 1A).A 3.0-T MR Scanner (Achieva; Philips, Zurich, Switzerland) with proton density turbo spin-echo SPectral Attenuated Inversion Recovery was applied to collect Caucasian images (slice thickness: 1.00 mm, voxel size 0.12 by 2.74 by 0.12 mm).3D models of femur and tibia were reconstructed using Amira 6.5 FEI SVG (Thermo Fisher, Stoney Creek, California, USA) according to proven and publicly available methods. 28,29With the same software, the ACL footprint areas of the femur and tibia were manually depicted on MRI images (Figure 1A). 30,31The subsequent analyses of the 3D models was completed by MATLAB2014.

Concept of the Distal Femur Coordinate System
A femur anatomical coordinate system (fACS) was developed based on a previously published method. 32The posterior articular surfaces of the medial and lateral condyles were best fitted and generated two fitted spheres, respectively.The best fitted spherical radius of the lateral condyle was defined as the width of the lateral femur condyle.The mediolateral (M/L) axis was parallel to the line connecting the center of these two fitted spheres.The fACS's M/L axis shared a common line with the flexion-extension axis (FEA) of the knee, 33,34 because several studies have reported that the cylindrical axis was consistent with the FEA of the knee.The anteroposterior (A/P) axis was perpendicular to both the M/L axis and the best-fitted cylinder of distal femoral shaft.The distal-proximal (D/P) axis of the fACS was perpendicular to both the ML axis and the AP axis.The coordinate system originated from the midpoint of the line connecting two condylar fitted spheres (Figure 1B). 35

Description of Measurement Indicators
The centers of femoral and tibial ACL footprints were defined as the barycenter of the footprint surface areas.The locations of the femoral ACL footprint were represented by its distance from the origin in the A/P and D/P directions.These distance values were measured in the software described above, generating values in millimeters and keeping only one decimal place.The normalized location of the femoral footprint was determined by dividing the length in the A/P and D/P directions by the best fitted spherical radius of the lateral condyle, respectively.Positive values represented a more anterior and proximal position relative to the origin of the fACS (or FEA).The ACL vector was defined as the line connecting the centers of the femoral and tibial ACL footprint.The orientation of the ACL was described with the angles of sagittal plane elevation, coronal plane elevation, and transverse plane deviation angles (Figure 2).Sagittal plane elevation (α) was defined as the angle between the ACL vector projected onto the sagittal plane of the tibia and the tibial AP axis. 36Coronal plane elevation (β) was defined as the angle between the ACL vector projected onto the coronal plane of the tibia and the tibial ML axis. 37Transverse plane deviation (θ) was defined as the angle between the projection of the ACL on the tibial plateau and the tibial AP axis. 38atistical Analysis G*Power version 3.1 (Franz Faul, University of Kiel, Germany) was used in the post-hoc power analysis for the statistical power (1 À β) estimation, with a medium effect size and α = 0.05.Descriptive statistics described all

FIGURE 2
The ACL orientation at full extension position is quantified.The coronal plane elevation angle (β) was defined as the angle between the ACL projected onto the coronal plane of the tibia and the mediolateral axis of the coordinate system.The sagittal plane elevation angle (α) was defined as the angle between the ACL projected onto the sagittal plane of the tibia and the anterior-posterior axis.The transverse plane deviation angle (θ) was defined as the angle between the projection of the ACL on the tibial plateau and the anterior-posterior axis.ACL, anterior cruciate ligament.
analyses.The result with a p value <0.05 was considered having statistical significance.

Power Analysis and Reliability Analysis
Statistical power to identify differences in ACL femoral attachment in each group were 95% both for the A/P and D/P locations.The intra and interobserver ICC of all the groups fell in the range of 0.82 to 0.93.

ACL Femoral Footprint
The average A/P position of the ACL femoral footprint was À6.6 AE 1.6 mm in the Chinese group and À5.1 AE 2.3 mm in the Caucasian group ( p < 0.001) (Figure 3).The normalized A/P position of the ACL femoral footprint was located at a mean of 32.1 AE 6.7% and 26.0 AE 11.9% posterior to the FEA of the knee in the Chinese and Caucasian groups (p < 0.001)     4) (Figure 5).

Orientation of the ACL
The mean angle of sagittal plane elevation was 51.8 AE 5.7 in the Chinese group and 51.9 AE 6.1 in the Caucasian group (p = 0.921).The mean angle of coronal plane elevation was 66.0 AE 6.  3).And the result for the Caucasian males and females was 53.3 AE 6.  4).

Multiple Regression Analysis
There were multiple linear correlations between the ACL orientation and the femoral footprint location.There was a negative linear correlation between sagittal angle and the femoral footprint position in the A/P and D/P directions (p = 0.004, p = 1.44eÀ09).For every 1% (0.40 mm) increase in A/P and D/P values, sagittal angle decreased by about 0.12 and 0.24 , respectively.There was also a negative linear correlation between coronal angle and the ACL femoral footprint position in the A/P and D/P directions ( p = 0.045, p = 1.51eÀ09).For every 1% (0.40 mm) increase in A/P and D/P values, coronal angle decreased by about 0.10 and 0.30 , respectively.There was a positive linear correlation between the transverse angle and the ACL femoral footprint position in the D/P direction (p = 0.018).For every 1% (0.40 mm) increase in the D/P value, the transverse angle increased by about 0.14 (Table 5).Scatter plots were used to visualize the regression correlations (Figures 6-8).The 95% CI was β AE std., and the Regression F-statistic was 164 (p < 0.001).

Significant Race and Gender Difference in Anterior Cruciate Ligament Femoral Footprint Location and Orientation
In this study, 3D-MRI images were used to find out whether there were significant differences between race and gender in  the ACL femoral attachment and the ACL orientation, and to analyze the relationship between ACL orientation and ACL femoral attachment.There was a significant race-specific difference in femoral footprint locations.Compared with the Caucasian group, the Chinese group had a mean difference of an 1.5 mm (6.1%) more posterior and 1.1 mm (5.3%) more proximal position from the FEA.The Chinese male had a mean 1.3 mm (2.6%) more posterior position from the FEA as compared with the Chinese female, but no gender-specific difference was found about the normalized femur footprint locations in the Caucasian group.It was also demonstrated that a significant gender-specific difference existed in the ACL orientation, with the sagittal plane elevation angle being 4-5 higher in males than in females, regardless of races.Furthermore, the coronal angle and sagittal angle were negatively correlated with the A/P and D/P values.For every 1% (0.40 mm) increase in A/P and D/P values, the sagittal angle decreased by about 0.12 and 0.24 , respectively; the coronal angle decreased by about 0.10 and 0.30 , respectively.However, the transverse angle was positively correlated with the D/P value.For every 1% (0.40 mm) increase in D/P value, the transverse angle increased by about 0.14 .

Femur Footprint Location and ACL Orientation
Individualized femoral tunnel positioning was still a research hotspot in anatomical single-bundle ACL reconstruction (Figure 9).Yamamoto et al. 14 reported a study of cadavers with an average age of 48.6 years, in which the    direction on average.Edwards et al. 34 reported a study with 22 elderly cadaver knees that the femur attachment center was located at 38.0% of the height and 41.5% of the depth based on the Amis' circle. 39In addition, Reid et al. 36 noted that the mean angle of inclination was 46.9 AE 4.9 in the sagittal plane and 74.3 AE 4.8 in the coronal plane based on MRI of 188 patients with intact ACLs.Freddie et al. 40,41 evaluated the native ACL sagittal angle was 49.9 AE 2.8 , and the femoral footprint was located at 27.5 AE 4.4% in the A/P direction and 38.5 AE 9.2% in the D/P direction.The femur footprint was located at 29.0% in the A/P direction and 16.5% in the D/P direction on average in the present study.(Tables 2-4).However, the current study also reported additional findings, namely, the femur footprint location was 1.5 mm (6.1%) more posterior and 1.1 mm (5.3%) more proximal in the Chinese group, especially, the Chinese males had a mean 1.3 mm (2.6%) more posterior position from the FEA as compared with the Chinese female, and the sagittal plane elevation angle was 4-5 higher in men than in women, regardless of race.
Previously Reported Grafts Generated by AM and TT Techniques Were Compared with Native ACLs in the Present Study In addition, anteromedial (AM) portal and transtibial (TT) drilling techniques were two common options for drilling femoral tunnels.3][44] Based on several studies, [45][46][47] the mean sagittal graft angle was 51.8 and 63.3 in the AM and TT groups, respectively.Among these studies, Guler et al. 38 additionally reported that according to the quadrant method the graft insertion was located at 31.33% with AM technology and 29.53% with TT technology in the A/P direction.In a comparative study of X-ray plain radiographs obtained from 404 patients undergoing ACL reconstruction, Gabr et al. 39 found the mean femoral tunnel position along the Blumensaat's line relating to the posterior femoral cortex was 16% in the AM group versus 22% in the TT group; the mean graft coronal inclination angle was 31.9 in the AM group and 22 in the TT group.In the present study, our results were similar to theirs (Tables 2-4).It was worth noting that the mean sagittal orientation of the native ACL (51.85 in this study) was more similar to the graft angle of the AM technique (51.80 from the literature).And there was no racespecific difference in the ACL orientation, but males have a sagittal plane elevation about 4-5 higher than females in different race groups, respectively (Tables 2-5).The results of the current study suggested that surgeons should pay special attention to the race-specific differences in the femoral ACL footprint and gender-specific in the orientation of ACL when individually customizing bone tunnels for patients.

The Anatomical Characteristics of Native ACL Might Have Implications for ACL Injury and Surgical Reconstruction
In a cadaveric study comparing anterior and rotational stability between conventional single-bundle ACL reconstruction and anatomical fibers, Brophy et al. 40 confirmed that a more posteriorly located femoral graft (posterolateral placement) could be more susceptible to apparent strain in extension or internal rotation.This might also be attributable to the high failure rate in the posterolateral bundle of the double-bundle reconstruction. 419][50][51][52] In the Chinese group, a more posteriorly and proximally located femoral ACL footprint might increase the risk of ACL injury, and a larger ACL inclination angle in males than in females might be correlated with a higher risk of ACL injury in non-athlete males, 53,54 owing to the altered kinematics and loading mechanics during a noncontact injury.However, the report on ACL injury rate in Chinese non-athletes was still limited.The results of the relationship between the ACL footprint location and the orientation might be useful to evaluate the current tunnel positions and determine the preoperative planning.In particular, for patients with graft failure, abnormal graft inclination and postoperative complications, our findings may provide a reference for surgeons to develop the revision operative strategy.

Limitations
This study should be interpreted in consideration of its limitations.First, MRI-based 3D models were used to identify the femoral and tibial footprints.Even though cadaveric studies were considered as the gold standard, the 3D-MRI has been proven to be an accurate and reliable imaging method 27,55,56 in that setting and larger populations could be included.Moreover, since the subjects in this study were Chinese and Caucasian with intact ACLs, further studies should include patients with ACL injury from different ethnic groups.

Conclusion
T he significant race-and gender-specific differences in the femoral footprint and orientation of the ACL should be taken in consideration during anatomic single-bundle ACL reconstruction.Furthermore, the quantitative relationship between ACL orientation and ACL footprint location might be useful for surgeons to evaluate the current tunnel positions, determine the preoperative planning, and develop the revision operative strategy.
FIGURE1(A) Proton density 3D fast spin-echo volume sequences (PD space) were applied to collect high-resolution volumetric MR images, the ACL footprint position is marked with an asterisk.(B) Three-dimensional surface models of the femur, tibia and ACL were reconstructed.The anatomic coordinate system of the femur is constructed.The origin is shown with a black circle; the mediolateral axis, connecting the center of the best-fitted spheres on the posterior articular surface of the medial and lateral condyles, is shown with a blue line.The distal-proximal is demonstrated with a red arrow and the anterior-posterior axis, a green arrow.The lateral femoral condyle width, defined as the radius of the best-fitted sphere in the lateral condyle, is shown with a black arrow.ACL, anterior cruciate ligament; MR, magnetic resonance.

FIGURE 3
FIGURE 3 The normalized femoral ACL footprint position (the centroid of the footprint surface area) of the Chinese group (red circle) and Caucasian group (blue circle) in the anterior-posterior and distalproximal direction are demonstrated.Chinese group, with a mean difference of an 6.1% more posterior and 5.28% more proximal position from the FEA.ACL, anterior cruciate ligament.

FIGURE 4
FIGURE 4 The normalized femoral ACL footprint position (the centroid of the footprint surface area) of the Chinese male group (blue circle) and female group (red circle) in the anterior-posterior and distalproximal direction are demonstrated.The Chinese male had a mean 2.65% more posterior position from the FEA as compared with the Chinese female.ACL, anterior cruciate ligament.
3 and 66.5 AE 7.7 , respectively (p = 0.167), and the mean angle of transverse plane deviation was 30.5 AE 6.2 and 29.0 AE 9.4 , respectively (p = 0.251) (Table 2).Similarly, the mean angle of sagittal plane elevation was 53.0 AE 5.6 in the Chinese males and 49.0 AE 4.8 in the Chinese females (p = 0.001).The mean angle of coronal plane elevation was 65.8 AE 7.6 and 63.1 AE 7.1 , respectively (p = 0.110), and the mean angle of transverse plane deviation was 30.6 AE 6.4 and 30.2AE 5.9 , respectively (p = 0.799) (Table

FIGURE 5
FIGURE 5 The normalized femoral ACL footprint position (the centroid of the footprint surface area) of the Caucasian male group (blue circle) and female group (red circle) in the anterior-posterior and distalproximal direction are demonstrated.No gender-specific difference was found in the normalized femur footprint locations with the Caucasian group.ACL, anterior cruciate ligament.

FIGURE 6
FIGURE 6 Scatter-plot of the correlation between location and transverse orientation.

FIGURE 7
FIGURE 7 Scatter-plot of the correlation between location and sagittal orientation.

FIGURE 8
FIGURE 8 Scatter-plot of the correlation between location and coronal orientation.

FIGURE 9
FIGURE 9 The normalized femoral ACL footprint position in the anteriorposterior and distal-proximal direction in Chinese group (red circle); and Caucasian group (blue circle) is demonstrated.The mean position of the femoral ACL footprint reported in the literature is also shown (green circle) based on the quadrant method.The black circle indicates the origin (or flexion extension axis) of the femoral coordinate system.ACL, anterior cruciate ligament.

TABLE 4
ACL femur footprint location and orientation between Caucasian males and females