Computer-Assisted System in Stress Radiography for Anterior Cruciate Ligament Injury with Correspondent Evaluation of Relevant Diagnostic Factors

diagnostics

Article Computer-Assisted System in Stress Radiography for Anterior Cruciate Ligament Injury with Correspondent Evaluation of Relevant Diagnostic Factors

Chien-Kuo Wang 1, Liang-Ching Lin 2, Yung-Nien Sun 3, Cheng-Shih Lai 1, Chia-Hui Chen 4,* and Cheng-Yi Kao 1,*

1 Department of Medical Imaging, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No. 1 University Rd, Tainan 704, Taiwan; [email protected] (C.-K.W.); [email protected] (C.-S.L.) 2 Department of Statistics, National Cheng Kung University, No. 1 University Rd, Tainan 704, Taiwan; [email protected] 3 Department of Computer Science and Information Engineering, National Cheng Kung University, No. 1 University Rd, Tainan 704, Taiwan; [email protected] 4 Department of Medical Imaging and Radiological Sciences, I-Shou University, No.8, Yida Rd., Jiaosu Village, Yanchao District, Kaohsiung City 82445, Taiwan * Correspondence: [email protected] (C.-H.C.); [email protected] (C.-Y.K.); Tel.: +886-7-6151100#7802 (C.-H.C.); +886-6-2766108 (C.-Y.K.); Fax: +886-7-6155150 (C.-H.C.); +886-6-2766608 (C.-Y.K.)

Abstract: We sought to design a computer-assisted system measuring the anterior tibial translation in stress radiography, evaluate its diagnostic performance for an anterior cruciate ligament (ACL) tear, and assess factors affecting the diagnostic accuracy. Retrospective research for patients with both Citation: Wang, C.-K.; Lin, L.-C.; knee stress radiography and magnetic resonance imaging (MRI) at our institution was performed. A Sun, Y.-N.; Lai, C.-S.; Chen, C.-H.; complete ACL rupture was conﬁrmed on an MRI. The anterior tibial translations with four different Kao, C.-Y. Computer-Assisted System methods were measured in 249 patients by the designed algorithm. The diagnostic accuracy of each in Stress Radiography for Anterior method in patients with all successful measurements was evaluated. Univariate logistic regression Cruciate Ligament Injury with analysis for factors affecting diagnostic accuracy of method four was performed. In the inclusive 249 Correspondent Evaluation of patients, 177 patients (129 with completely torn ACLs) were available for analysis. Mean anterior Relevant Diagnostic Factors. tibial translations were signiﬁcantly increased in the patients with a completely torn ACL by all four Diagnostics 2021, 11, 419. https:// doi.org/10.3390/diagnostics11030419 methods, with diagnostic accuracies ranging from 66.7% to 75.1%. The diagnostic accuracy of method four was negatively associated with the time interval between stress radiography and MRI as well as

Academic Editor: Ingrid Moller force-joint distance on stress view, and not signiﬁcantly associated with age, gender, ﬂexion angle, intercondylar distance, and force-joint angle. A computer-assisted system measuring the anterior Received: 24 December 2020 tibial translation in stress radiography showed acceptable diagnostic performance of complete ACL Accepted: 26 February 2021 injury. A shorter time interval between stress radiography and MRI as well as shorter force-joint Published: 2 March 2021 distance were associated with higher diagnostic accuracy.

Publisher’s Note: MDPI stays neutral Keywords: knee; anterior cruciate ligament; ACL; stress radiography; computer-aided diagnosis with regard to jurisdictional claims in published maps and institutional affil- iations. 1. Introduction The anterior cruciate ligament (ACL) is the main restraint of anterior tibial translation. It may be torn when taking unexpected heavy loading, e.g., strenuous exercise or traffic Copyright: © 2021 by the authors. accident, thereby causing knee instability [1]. Therefore, early diagnosis of ACL tear Licensee MDPI, Basel, Switzerland. is crucial. Magnetic resonance imaging (MRI) with high resolution and good imaging This article is an open access article quality is helpful for confirming the diagnosis of the ACL tear, but it is expensive and distributed under the terms and time-consuming [2]. Clinical diagnosis of ACL tear is still important. conditions of the Creative Commons The clinical diagnosis of ACL tear is based on anterior tibial translation by applying Attribution (CC BY) license (https:// a different force to the knee. The anterior drawer test is subjective, unmeasurable, and creativecommons.org/licenses/by/ 4.0/). not well reproducible [3]. Stress radiography of the knee offers a relatively objective and

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measurable approach to quantify the anterior tibial translation when applying force to the knee [4–7]. A prior study has focused on the effect of knee position on the reproducibility of measurements taken from stress radiography [8]. A different knee flexion angle, injury extent, muscle guarding, and femoral rotation affect the laxity measurement using stress radiography [4,9,10]. Another study compared different measuring methods and assessed the intra-class correlation coefficient of each method to evaluate the knee instability [11]. However, the reliability of manual measurements done by different readers and different methods is questionable. Several automatic methods for objective measurement of joint space or angle using computer-assisted systems have recently been developed [12–14]. Automatic computer image assessment and analysis system can segment the femur, tibia, and patella using an edge-based method. Then, some landmarks to calculate tibial translation distance can be defined using a segmentation algorithm. In this study, we designed a computer-assisted system that automatically segmented bone contours of the knee and, subsequently, measured the distance of anterior tibial translation in stress radiography. The diagnostic performances of different methods for ACL injury were evaluated. It was hypothesized that we could use our computer-assisted system to (1) evaluate the diagnostic performance of stress radiography for ACL insufficiency by different measurement methods, and (2) assess the effects of age, gender, time interval between stress radiography and MRI, and technical factors on the diagnostic accuracy.

2. Materials and Methods 2.1. Patients Institutional Review Board approval was obtained, and the requirement to obtain informed consent was waived. A retrospective search of the Picture Archiving and Com- munication System (PACS) for patients with both knee stress radiography by Telos device (Metax, Hungen, Germany) and MRI at our institution was performed. The MRI was reviewed by one musculoskeletal radiologist, and the status of ACL was classiﬁed into complete tear, partial tear, or no tear. If the review did not match the previous report, a musculoskeletal radiologist with more than 20 years of experience made the ﬁnal decision. The patients were divided into one group with a complete ACL tear, and another group without a complete ACL tear. The time interval between stress radiography and MRI was recorded. A total of 399 patients with stress radiography and MRI for evaluation of ACL injury were included in this study, from which 150 patients were excluded (Figure1). In addition, 28 patients were diagnosed as multiple ligamentous injuries on MRI, while 15 patients with the torn meniscus had displaced fragments. Nine patients were excluded due to long interval (>9 weeks) between stress radiography and MRI. Furthermore, 27 patients were excluded due to anatomic shape changes by severe osteoarthritis, fractures, or intraar- ticular loose bodies, 36 patients were excluded due to a previous knee surgery, 18 patients were excluded because of unsatisfactory device position to obscure the segmentation, and another 17 patients were excluded due to poor image quality. Imaging data processing and a tibial translation measurement were performed in the remaining 249 patients. Diagnostics 2021, 11, 419 3 of 11 Diagnostics 2021, 11, x FOR PEER REVIEW 3 of 11

FigureFigure 1. TheThe flow flow chart chart of of patient inclusion and exclusion. 2.2. Knee Segmentation 2.2. Knee Segmentation Lateral projection views of the knee before and after exerting a force of 15 daN (1 Lateral projection views of the knee before and after exerting a force of 15 daN (1 daN = 10 N), in accordance with a previous study [15], posteriorly on the tibia by a daN = 10 N), in accordance with a previous study [15], posteriorly on the tibia by a stress stress device were taken. In the automatic measurement of knee translation in stress device were taken. In the automatic measurement of knee translation in stress radiog- radiography, the most important and challenging part was knee segmentation (Figure2). raphy,We first the performed most important down sampling and challenging of the images part was to improve knee segmentation the efficiency (Figure of following 2). We firstpre-processing. performed down Then, thesampling Gaussian of the smoothing images to is improve applied tothe the efficiency images forof following noise removal, pre- processing.making the Then, edge ofthe the Gaussian bone relatively smoothing clear is by applied removing to the artifactimages infor the noise image. removal, Since makingthe knee the joint edge is located of the bone between relatively two major clear bony by removing structures the (femur artifact and in tibia),the image. a less Since bony thestructure knee joint meant is located less brightness. between two For everymajor rowbony in structures the image, (femur the sums and oftibia), allgray a less values bony structurewere computed. meant less The brightness. row with a localFor every minimum row in was the determined image, the assums the kneeof all joint gray location values wereand takencomputed. as a reference The row position.with a local To minimu segmentm thewas contours determined in the as complexthe knee joint X-ray location image, andwe usedtaken the as frameworka reference ofposition. minimal To intensity segment andthe contours a shape cost in the path complex model X-ray proposed image, by weD. Seghersused the etframework al. [16]. The of minimal anterior intensity edge and an thed a posterior shape cost edge path of model both femurproposed and by tibia D. Segherswere segmented et al. [16]. and The used anterior to calculate edge and the the femoral posterior axis andedge the of tibialboth axisfemur by and the bonetibia were edge segmentedmodel. The and femoral used axis to calculate was drawn the as femoral the midline axis ofand the the anterior tibial axis and posteriorby the bone edges edge of model.the femur The between femoral anaxis 8–14-cm was drawn distance as the away midline from of the the joint anterior space, and while posterior the tibial edges axis of thewas femur drawn between similarly. an Afterward, 8–14-cm distance the joint away position from and the femoraljoint space, axis while were usedthe tibial to define axis wasthe regiondrawn ofsimilarly. interest (ROI)Afterward, for femoral the joint condyles. position Aand condyle, femoral which axis were is most used fitted to define to the theappearance region of and interest shape (ROI) in the for image, femoral is segmented. condyles. A The condyle, femoral which condyle is most model fitted was to built the appearancefrom a set of and training shape images in the basedimage, on is thesegm frameworkented. The of femoral the appearance condyle modelmodel andwas shape built frommodel a set proposed of training by D. images Seghers based et al. on [16 the]. Theframework condyle of contour the appearance was segmented model and within shape the modelROI by proposed the femoral by D. condyle Seghers model. et al. [16]. Finally, The we condyle could contour define the was landmark segmented points within on the ROIbone by axes the and femoral condyle condyle contours model. (Figure Finally,3). we could define the landmark points on the bone axes and condyle contours (Figure 3).

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FigureFigureFigure 2. 2.2. The TheThe flow ﬂowflow chart chartchart of ofof knee kneeknee segmentation. segmentation.segmentation.

Figure 3. The segmentation results of stress radiography for anterior cruciate ligament (ACL) in- FigureFigure 3. 3. TheThe segmentation segmentation results results of of stress stress radiogra radiographyphy for anterior cruciate ligament (ACL) injury.injury. In this case, the lateral (lat) projection views of the right (R) knee before and after exerting a jury.In this In case,this case, the lateralthe lateral (lat) (lat projection) projection views views of the of the right right (R) (R knee) knee before before and and after after exerting exerting a force a forceforce of of 15 15 daN daN (+15D) (+15D) posteriorly posteriorly on on the the tibia tibia by by a astress stress device device were were taken. taken. The The anterior anterior edge edge and and of 15 daN (+15D) posteriorly on the tibia by a stress device were taken. The anterior edge and the thethe posterior posterior edge edge of of both both femur femur and and tibia tibia were were segmented segmented (cyan (cyan and and orange orange dots) dots) and and used used to to posterior edge of both femur and tibia were segmented (cyan and orange dots) and used to calculate calculatecalculate the the femoral femoral axis axis and and the the tibial tibial axis axis (cya (cyann and and orange orange straight straight lines). lines). The The condyle condyle contours contours (whitethe(white femoral and and yellow axisyellow and curves) curves) the tibial were were axis also also (cyan segmented. segmented. and orange straight lines). The condyle contours (white and yellow curves) were also segmented. 2.3.2.3. Methods Methods to to Measure Measure Tibial Tibial Translation Translation FourFour methods methods measuring measuring the the anterior anterior tibial tibial translation translation were were adopted adopted in in this this study. study. TheThe first first two two methods methods were were introduced introduced by by Wirz Wirz et et al. al. [8], [8], and and the the latter latter two two methods methods were were

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proposed by this study. The peripheral landmarks are shown as inaccurate if the rotation is changed, and central methods are the most affected if flexion is altered [17]. In all four methods, the femoral reference location and the tibial position were defined. Finally, the tibial translation was determined as the change in the tibial position. The central measurement (method 1) is illustrated in Figure 4A. The points where the femoral axis intersected the margins of the medial and lateral femoral condyles were found, and the femoral reference point was defined as the midpoint of the two intersection points. The tibial position was defined as the distance between the femoral reference point and the tibial axis. A combined central-peripheral measurement (method 2) is illustrated in Figure 4B. The lines parallel to the tibial axis and tangential to the posterior margins of the medial and lateral femoral condyles were drawn, and the femoral reference line was defined as the midline of the two tangent lines. The tibial position was defined as the distance between the femoral reference line and the tibial axis. Femoral condyle tangent measurement (method 3) was modified from method 2 and Diagnostics 2021, 11, 419 illustrated in Figure 4C. Instead of using a line parallel to the tibial axis, the5 of lines 11 parallel to the femoral axis and tangential to the posterior margins of the medial and lateral femoral condyles were drawn, and the femoral reference point was defined as the midpoint of the two tangent points. The tibial position was defined as the distance of the femoral 2.3. Methods toreference Measure point Tibial and Translation the tibial axis. Four methodsThe measuring condyle center the anterior measurement tibial translation (method 4) werewas newly adopted proposed in this and study. is illustrated The first two methodsin Figure 4D. were The introduced landmarks by that Wirz represented et al. [8], andthe medial the latter and two lateral methods femoral were condyle mar- proposed by thisgins study.were first The defined peripheral by a landmarks femoral condyle are shown model. as The inaccurate center points if the rotationof the medial and is changed, andlateral central femoral methods condyle are landmarks the most affected were obtained, if flexion and is altered the femoral [17]. Inreference all four point was methods, thedefined femoral as reference the midpoint location of the and two the center tibial positionpoints. The were tibial defined. position Finally, was defined the as the tibial translationdistance was determinedof the femoral as reference the change point in theand tibial the tibial position. axis. The central measurementIn all four methods, (method the 1)segmentation is illustrated results in Figure were4 reviewedA. The points by one where musculoskeletal the femoral axisradiologist intersected to search the margins for inappropriate of the medial landmarks and lateral (femoral femoral axis, condyles tibial axis, were and the mar- found, and thegins femoral of femoral reference condyles) point obtained was defined by the as se thegmentation midpoint ofalgorithms. the two intersection The segmentation re- points. The tibialsult positionof each measurement was defined asmethod the distance was only between considered the femoral successful reference if all landmarks point were and the tibialappropriate. axis.

Figure 4. FourFigure measurement 4. Four measurement methods. The methods. femoral Theaxis femoral(FA) and axis the (FA) tibial and axis the (TA) tibial were axis drawn (TA) were first. drawn(A) In ﬁrst.method 1, the midpoint(A of) the In method intersection 1, the points midpoint of the of femoral the intersection axis and the points femoral of the condyl femoralar edges axis andwas thethe femoralfemoral condylarreference point (Ref). (B) In method 2, the midline of the lines tangential to posterior femoral condylar edges and parallel to TA was the edges was the femoral reference point (Ref). (B) In method 2, the midline of the lines tangential femoral reference line (Ref). (C) In method 3, the midpoint of the tangent points of the lines tangential to posterior femoral condylar edgesto posterior and parallel femoral to FA condylarwas the femoral edges reference and parallel point to (Ref). TA was (D) the In method femoral 4, reference the midpoint line of (Ref). the center (C) In points method 3, the midpoint of the tangent points of the lines tangential to posterior femoral condylar edges and parallel to FA was the femoral reference point (Ref). (D) In method 4, the midpoint of the center points of the medial and lateral femoral condyle landmarks was the femoral reference point (Ref). Finally, in all four methods, the distance between the TA and Reference was the tibial position (TP).

A combined central-peripheral measurement (method 2) is illustrated in Figure4B. The lines parallel to the tibial axis and tangential to the posterior margins of the medial and lateral femoral condyles were drawn, and the femoral reference line was defined as the midline of the two tangent lines. The tibial position was defined as the distance between the femoral reference line and the tibial axis. Femoral condyle tangent measurement (method 3) was modified from method 2 and illustrated in Figure4C. Instead of using a line parallel to the tibial axis, the lines parallel to the femoral axis and tangential to the posterior margins of the medial and lateral femoral condyles were drawn, and the femoral reference point was defined as the midpoint of the two tangent points. The tibial position was defined as the distance of the femoral reference point and the tibial axis. The condyle center measurement (method 4) was newly proposed and is illustrated in Figure4D. The landmarks that represented the medial and lateral femoral condyle margins were first defined by a femoral condyle model. The center points of the medial and lateral Diagnostics 2021, 11, 419 6 of 11

femoral condyle landmarks were obtained, and the femoral reference point was deﬁned as the midpoint of the two center points. The tibial position was deﬁned as the distance of the femoral reference point and the tibial axis. In all four methods, the segmentation results were reviewed by one musculoskeletal radiologist to search for inappropriate landmarks (femoral axis, tibial axis, and the margins of femoral condyles) obtained by the segmentation algorithms. The segmentation result of each measurement method was only considered successful if all landmarks were appropriate.

2.4. Measurements of Technical Factors Stress radiography of the knee could be affected by various technical factors. Changes in flexion and rotation occur as the knee joint is stressed. To investigate the technical factors affecting the result of tibial translation in stress radiography, we additionally measured the knee flexion angle, intercondylar distance, force-joint distance, and force-joint angle. The knee flexion angle was defined as the angle between the femoral axis and the tibial axis. The intercondylar distance was defined as the distance between the center points of the medial and lateral femoral condyle landmarks segmented by the femoral condyle model. The force-joint distance was defined as the distance between the tibial plateau and the skin point at the posterior load central line, and reported as positive and negative values for the skin point below and above tibial plateau respectively. The force-joint angle was defined as the angle between the tibial plateau and the posterior load central line, and reported as positive and negative values for the direction of force toward and away from the tibial plateau, respectively.

2.5. Statistical Analysis Analyses were conducted using statistical software (R for Windows, version 3.5.2). The receiver operating characteristic (ROC) curves were performed to illustrate the diagnostic abilities of these four methods. The optimal thresholds and cutoff points were obtained by finding the maximum Youden’s J statistic, which was defined as the sums of sensitivity and specificity subtracting 1. Youden’s J statistic ranged from zero to one with larger values representing better performance. From these cutoff points, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for all four methods. Sample size calculation was based on the area under the ROC curve (AUC) of 0.8 for stress radiography with the Telos device used in a previous study [9]. An α error of 5% and a ß error of 20% were accepted to detect any significant difference. On the basis of these calculations, the required sample size was 28 per group, with a 0.5 null hypothesis value and a 1:1 allocation. To evaluate the effect of different factors on the accuracy, we chose method four, a central measuring method, to minimize the effect of knee rotation during stress. We built a logistic regression model. The odds ratios and the corresponding 95% confidence intervals were evaluated to quantify the strength of the association between each factor and the judgement of method four. Continuous variables were reported as means ± standard deviations and analyzed with the t-test, whereas categoric variables were analyzed with the chi-square or Fisher’s exact test. A p value ≤ 0.05 was considered significant.

3. Results This section may be divided by subheadings. It should provide a concise and precise description of the experimental results, their interpretation, and the experimental conclusions that can be drawn. In the inclusive 249 patients, the successful numbers of knee segmentation and tibial translation measurement were 228, 216, 233, and 200 patients by methods one, two, three, and four, respectively, with successful rates ranging from 80.3% to 91.6%. Examples of unsuccessful cases are shown in AppendixA. The ﬁnal data available Diagnostics 2021, 11, 419 7 of 11 Diagnostics 2021, 11, x FOR PEER REVIEW 7 of 11

for analysis were derived from the 177 patients (mean age ± standard deviation, 28.4 The patient characteristics of our study were summarized in Table 1. Among the 177 pa- years ± 10.5, age range, 16–68 years) with successful measurements by all four methods. tients (144 males and 33 females), completely torn ACLs were found in 129 patients. The The patient characteristics of our study were summarized in Table1. Among the 177 mean interval between stress radiography and MRI was 20.44 days. patients (144 males and 33 females), completely torn ACLs were found in 129 patients. The The mean tibial translation measurements were 10.50 mm ± 5.27, 10.58 mm ± 4.83, mean interval between stress radiography and MRI was 20.44 days. 8.85 mm ± 5.02, and 9.78 mm ± 4.89 for patients with completely-torn ACL by all four methodsTable 1. Clinical sequentially data in and 177 patientsrespectively. with knee However, stress radiographies. those were 6.49 mm ± 3.46, 6.77 mm ± 3.17, 5.07 mm ± 2.80, and 5.82 mm ± 2.93 for patients without completely torn ACL by the four methods respectively.Parameter The differences between patients with Value and without complete ACL injury were Meanall significant age (y) for the four methods (p < 0.001). 28.4 ± 10.5 (16–68) The ROC curvesMale gendershowing * the diagnostic abilities of all four 144 measurement (81.4) methods wereInterval illustrated between in Figure stress view 5. The and AUCs MRI (d) of methods 1 to 4 20.44 were± 13.800.733, (0–61) 0.752, 0.744, and ◦ 0.765, respectively.Flexion angle The ( ) optimal on stress viewthresholds and cutoff points 38.47 ± (maximum11.22 (11.88–63.86) Youden’s J sta- ± tistic)Intercondylar of methods distance 1 to 4 (mm) were on 6.16 stress mm, view 7.47 mm, 6.41 mm, 4.53 and3.61 3.97 (0–16.73) mm, respectively. Force-joint distance (mm) on stress view 39.70 ± 11.74 (11.19–67.22) Based onForce-joint these optimal angle ( ◦thresholds,) on stress view the diagnostic performances−10.58 ± 9.30 of (all−32.14–12.51) four measurement methods wereTorn shown ACL in on Table MRI *2. The accuracies of the four methods 129 (72.9) were 75.1%, 71.2%, 66.7%,Note—Unless and 72.9%, otherwise respectively. indicated, data are reported as means and standard deviations, with ranges in parentheses. * Data are numbers of cases, with percentages in parentheses. Table 1. Clinical data in 177 patients with knee stress radiographies. The mean tibial translation measurements were 10.50 mm ± 5.27, 10.58 mm ± 4.83, Parameter Value 8.85 mm ± 5.02, and 9.78 mm ± 4.89 for patients with completely-torn ACL by all four meth- Mean age (y) 28.4 ± 10.5 (16–68) ods sequentially and respectively. However, those were 6.49 mm ± 3.46, 6.77 mm ± 3.17, 5.07 mm ± 2.80, andMale 5.82 gender mm ± *2.93 for patients without completely 144 torn (81.4) ACL by the four methodsInterval respectively. between stress The differences view and MRI between (d) patients with 20.44 and without± 13.80 (0–61) complete ACL injury wereFlexion all signiﬁcant angle (°) for on thestress four view methods (p < 0.001). 38.47 ± 11.22 (11.88–63.86) IntercondylarThe ROC curves distance showing (mm) the on diagnostic stress view abilities of all 4.53 four ± measurement 3.61 (0–16.73) methods were illustratedForce-joint indistance Figure5 (mm). The AUCson stress of methodsview 1 to 4 were 39.70 0.733, ± 11.74 0.752, (11.19–67.22) 0.744, and 0.765, respectively.Force-joint The optimal angle (°) thresholds on stress and view cutoff points (maximum−10.58 ± 9.30 Youden’s (−32.14–12.51)J statistic) of methods 1 to 4Torn were ACL 6.16 mm,on MRI 7.47 * mm, 6.41 mm, and 3.97 mm, 129 respectively. (72.9) Based on Note—Unlessthese optimal otherwise thresholds, indicated, the diagnostic data are repo performancesrted as means of and all standard four measurement deviations, with methods rangeswere shownin parentheses. in Table *2 Data. The are accuracies numbers of of the cases, four with methods percentages were 75.1%, in parentheses. 71.2%, 66.7%, and 72.9%, respectively.

FigureFigure 5. 5.The The receiver receiver operating operating characteristic characteristic (ROC) (ROC) curves curves of of all all four four measurement measurement methods. methods.

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Table 2. Diagnostic performance of knee stress radiography for the detection of anterior cruciate ligament tear.

Sensitivity Speciﬁcity PPV NPV Accuracy percentage (95% conﬁdence interval) 106/129, 82.2 27/48, 56.3 106/127, 83.5 27/50, 54.0 133/177, 75.1 Method 1 (76.5–87.8) (48.9–63.6) (78.0–88.9) (46.7–61.3) (68.8–81.5) 94/129, 72.9 32/48, 66.7 94/110, 85.5 32/67, 47.8 126/177, 71.2 Method 2 (66.3–79.4) (59.7–73.6) (80.3–90.6) (40.4–55.1) (64.5–77.9) 80/129, 62.0 38/48, 79.2 80/90, 88.9 38/87, 43.7 118/177, 66.7 Method 3 (54.9–69.2) (73.2–85.1) (84.3–93.5) (36.4–51.0) (59.7–73.6) 97/129, 75.2 32/48, 66.7 97/113, 85.8 32/64, 50.0 129/177, 72.9 Method 4 (68.8–81.6) (59.7–73.6) (80.7–91.0) (42.6–57.4) (66.3–79.4) Note—PPV = positive predictive value. NPV = negative predictive value.

A summary of the results of the univariate analyses for factors affecting diagnostic accuracy of method 4 was presented in Table3. Among these factors, the time interval between stress radiography and MRI (p = 0.035), and force-joint distance on stress view (p = 0.032) were negatively associated with the diagnostic accuracy of method 4. A decrease of 1 day in the interval between stress radiography and MRI could increase the diagnostic accuracy by 2.5%. For every 1-mm decrease in the force-joint distance on stress view, 3.3% improvement in diagnostic accuracy was shown. The factors including age, gender, ﬂexion angle, intercondylar distance, and force-joint angle were not signiﬁcantly related to the diagnostic accuracy using method 4 (p = 0.380, p = 0.681, p = 0.201, p = 0.971, and p = 0.637, respectively).

Table 3. Factors affecting diagnostic accuracy in knee stress radiographies evaluated by method 4.

Accurate Cases Error Cases Odds Ratio (95% CI) * β Value † p Value ‡ (TP + FN = 129) (FP + TN = 48) Age—y 28.85 ± 10.68 27.29 ± 10.00 1.016 (0.983–1.054) 0.015 0.380 Male gender—no. (%) 104 (80.62) 40 (83.33) 0.832 (0.328–1.930) −0.184 0.681 Interval between stress radiography and MRI—d 19.08 ± 13.75 24.08 ± 13.39 0.975 (0.952–0.998) −0.025 0.035 Flexion angle on stress view—◦ 37.82 ± 11.36 40.24 ± 10.74 0.980 (0.951–1.010) −0.020 0.201 Intercondylar distance on stress view—mm 4.54 ± 3.68 4.52 ± 3.46 1.000 (0.915–1.101) 0.002 0.971 Force-joint distance on stress view—mm 38.53 ± 11.48 42.84 ± 11.96 0.968 (0.938–0.996) −0.033 0.032 Force-joint angle on stress view—◦ −10.31 ± 9.28 −11.05 ± 9.50 1.009 (0.973–1.047) 0.009 0.637 Note—TP = true positive, FN = false negative, FP = false positive, TN = True negative, CI = confidence interval. *Estimates for categorical data are unadjusted odds ratios, and 95% confidence intervals are two-sided and were calculated with the use of Fisher’s exact tests. Estimates for continuous data are mean differences, and 95% confidence intervals were calculated with the use of t-tests. † Estimates are beta values of logistic regression models. When the factor increases by 1, the accuracy of method 4 will increase by eβ − 1. ‡ Estimates for categorical data were calculated with the use of Fisher’s exact tests. Estimates for continuous data were calculated with the use of t-tests.

4. Discussion The aim of the current study was to measure the anterior tibial translation of knee stress radiography using an automatic computer-assisted system. According to our retrospective study, the anterior tibial translation in the completely torn ACL patients was signiﬁcantly increased for all four different methods. Furthermore, we found that a shorter time interval between stress radiography and MRI, and closer force-joint distance were associated with higher diagnostic accuracy using a Condyle center measurement (method 4). Previous studies have shown that the ACL can regain continuity after partial or complete rupture [18–20]. In total, 42% of complete ruptures have been reported to regain continuity after three months [20] and 68% of partial ruptures can regain continuity after 6–36 months [19]. Progression and improvement of ACL tear between the two imaging examinations could contribute to the false negative and false positive cases. Therefore, the negative association between the time interval and diagnostic accuracy was depicted in our study. The effect of the force-joint distance could be explained by the fact that the force exerted on the knee joint in stress radiography was inevitably resorbed by the underlying Diagnostics 2021, 11, 419 9 of 11

muscles. A longer force-joint distance resulted in a softer tissue of the lower leg being compressed. Then less net force was exerted to the knee joint, which, in turn, lowered the diagnostic accuracy in our study. Computer-aided diagnosis (CAD) systems have been used to measure a tibio-femoral angle, joint space narrowing, and osteophyte formation for quantification of knee osteoarthritis severity in previous studies [12–14]. The reliability by any manual operation is questionable. The intra-rater and interrater intraclass correlation coefficients should be evaluated in manual measurements. The knee segmentation and landmark point definition in our study worked successfully in more than 80% of the cases for the four methods and are, thus, applied in clinical settings for feasibility in the future. Four different measurement methods for anterior instability in the stress radiography of knee joint were compared in our study. Wirz et al. have found that the central measuring method and central peripheral measuring method are less affected by internal and external rotation of the knee than the peripheral measuring method [8]. In our study, the methods could be categorized as a central measuring method (methods 1 and 4) and a central- peripheral measuring method (methods 2 and 3). The lower successful rate of method 4 than those of the other three methods might result from the complexity of the segmentation algorithm in the medial and lateral femoral condyle margins. However, the choices of different landmarks and methods in our study did not significantly influence the diagnostic accuracies and AUCs of the four methods. Lee HJ et al. have investigated how different knee flexion positions affect the diagnostic value of stress radiography for anterior instability and found that the AUCs of stress radiography at 30◦, 45◦, 60◦, and 90◦ positions are 0.897, 0.78, 0.665, and 0.432, respectively [9]. The tension of ACL increases as the knee flexion angle decreases from 45◦ to 0◦ with the greatest tension in the hyperextension. The negative correlation between the flexion angle and the diagnostic accuracy was shown in our study, but could not reach statistical significance. This could be explained by the fact that 71.8% of our cases had a flexion angle less than 45◦, and the mean knee flexion angle was 38.47◦. A negative correlation might be better shown if our data included more cases with flexion angles of more than 45◦. In this study, we used the distance of anterior tibial translation of the diseased knee to evaluate its anterior instability, instead of a side-to-side difference as in other previous studies [9,21–23]. In our institution, MRI is performed only on diseased knees in most cases. Therefore, the condition of ACLs of the contralateral knees could not be presumed to be normal. In a previous cadaveric study, medial meniscus posterior horn longitudinal tears ranging from 2.4 to 3.3 cm in ACL-deficient knees have resulted in a significant increase in anterior-posterior tibial translation at all flexion angles except 90◦ [24]. In our study, a non-displaced meniscus tear would not be the reason of the false negative case in detecting the ACL tear. However, the displaced fragments from a torn meniscus could cause locking of the knee joint during stress and, subsequently, reduce the tibial translation. Therefore, patients with displaced fragments of torn meniscus were selectively excluded in our study. Several issues result in limitations of this study. First of all, the study was retrospective and, therefore, prone to selection bias. Secondly, our algorithm could not clearly identify bone contours with metallic implants in the images, and, thus, had limited utility in postoperative cases. Thirdly, the timing of injury of the study population was unavailable, so further analysis about acute and chronic injury could not be performed. Finally, the reference standard of ACL tear in this study was based on MRI. The partial tear was not separately categorized because of insufficiency to differentiate a partial tear from mucoid degeneration of ACL only by MRI [15]. Moreover, the discrepancy between MRI and arthroscopy could lead to misclassification. Diagnostics 2021, 11, 419 10 of 11

Diagnostics 2021, 11, x FOR PEER REVIEW 10 of 11

5. Conclusions We have successfully designed a computer-assisted system, which automatically tic performance.measured the Further distance analysis of tibial showed translation a shorter in stress time radiography interval between with acceptable stress radiog- diagnostic raphyperformance. and MRI, and Further shorter analysis force-joint showed distance a shorter were time associated interval betweenwith higher stress diagnostic radiography accuracy.and MRI, and shorter force-joint distance were associated with higher diagnostic accuracy.

AuthorAuthor Contributions: Contributions: C.-K.W.C.-K.W. and andY.-N.S.: Y.-N.S.: revising revising the themanu manuscriptscript critically critically for forimportant important intel- intellec- lectualtual content. content. C.-H.C., C.-H.C., L.-C.L., L.-C.L., and and C.-S.L.: C.-S.L.: conception conception and and design. design. C.-Y.K.: C.-Y.K.: drafting drafting the the manu- manuscript. script.C.-H.C. C.-H.C. and and C.-Y.K. C.-Y.K. contributed contributed equally equally to thisto this manuscript. manuscript. All All authors authors have have read read and and agreed to the agreedpublished to the published version of version the manuscript. of the manuscript. Funding:Funding: This Thiswork work was wassupported supported by the by National the National Cheng Cheng Kung Kung University University Hospital, Hospital, Taiwan Taiwan [grant [grantnumber number NCKUH-10105015]. NCKUH-10105015]. InstitutionalInstitutional Review Review Board Board Statement: Statement: The studyThe study was conducted was conducted accordin accordingg to the to guidelines the guidelines of the of the DeclarationDeclaration of Helsinki of Helsinki and andapproved approved by the by Inst theitutional Institutional Review Review Board Board of National of National Cheng Cheng Kung Kung UniversityUniversity Hospital Hospital (NCKUH-10105015/ER-100- (NCKUH-10105015/ER-100-244,244, approved approved on 27 on December 27 December 2011). 2011). InformedInformed Consent Consent Statement: Statement: PatientPatient consent consent was was waived waived due due to to the the retrospective retrospective naturenature of of this this study. study. Data Availability Statement: The data presented in this study are available on request from the Datacorresponding Availability Statement: author. The data presented in this study are available on request from the corresponding author. Acknowledgments: The authors appreciated Ming-Jhe Huang for technical support. The research Acknowledgments:was supported in The part authors by Higher appreciated Education Ming-Jhe Sprout Project, Huang Ministry for technical of Education support. to The the research Headquarters was ofsupported University in part Advancement by Higher atEducation National Sprout Cheng KungProject, University Ministry (NCKU).of Education to the Head- quarters of University Advancement at National Cheng Kung University (NCKU). Conﬂicts of Interest: The authors declare no conﬂict of interest. Conflicts of Interest: The authors declare no conflict of interest. AppendixAppendix A A

(A) (B)

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