Original Article Evaluation of an automated superimposition method based on multiple landmarks for growing patients ABSTRACT Objectives: To determine if an automated superimposition method using six landmarks (Sella, Nasion, Porion, Orbitale, Basion, and Pterygoid) would be more suitable than the traditional SellaNasion (SN) method to evaluate growth changes. Materials and Methods: Serial lateral cephalograms at an average interval of 2.7 years were taken on 268 growing children who had not undergone orthodontic treatment. The T1 and T2 lateral images were manually traced. Three different superimposition methods: Björk’s structural method, conventional SN, and the multiple landmark (ML) superimposition methods were applied. Bjork’s structural method was used as the gold standard. Comparisons among the superimposition methods were carried out by measuring the linear distances between Anterior Nasal Spine, point A, point B, and Pogonion using each superimposition method. Multiple linear regression analysis was performed to identify factors that could affect the accuracy of the superimpositions. Results: The ML superimposition method demonstrated smaller differences from Björk’s method than the conventional SN method did. Greater differences among the cephalometric landmarks tested resulted when: the designated point was farther from the cranial base, the T1 age was older, and the more time elapsed between T1 and T2. Conclusions: From the results of this study in growing patients, the ML superimposition method seems to be more similar to Björk’s structural method than the SN superimposition method. A major advantage of the ML method is likely to be that it can be applied automatically and may be just as reliable as manual superimposition methods. (Angle Orthod. 0000;00:000–000.) KEY WORDS: Growth evaluation; Automatic superimposition method; Artificial intelligence comes of orthodontic treatment.1–3 Various superimposition methods using different reference planes have been developed.4–6 Depending on which references are used for superimpositions, assessment of treatment outcomes or growth change analysis can be different. Therefore, in comparing serial lateral cephalometric radiographs, the selection of references is fundamental. Especially in superimpositions of growing patients, stable structures that are not affected by growth should be selected as references.7 Meanwhile, owing to rapid development of artificial intelligence (AI), numerous research groups have been applying machine learning methods.8–14 The latest AI demonstrated a level of accuracy equivalent to humans when identifying cephalometric landmarks.10 Recently, an automatic superimposition method that can be implemented immediately after automatic landmark identification was proposed.15 Björk’s structural method has conventionally been recognized as the gold standard for superimposition in a growing patient. It depends on relatively stable INTRODUCTION Cephalometric superimposition has been used to evaluate changes associated with growth and outa Postgraduate Student, Department of Orthodontics, Graduate School, Seoul National University, Seoul, Korea. b Clinical Lecturer, Department of Orthodontics, Seoul National University Dental Hospital, Seoul, Korea. c Assistant Professor, Graduate Program Director, Department of Orthodontics, University of Florida College of Dentistry, Gainesville, FL, USA. d Professor, Department of Orthodontics and Dental Research Institute, Seoul National University School of Dentistry, Seoul, Korea. Corresponding author: Dr Shin-Jae Lee, Professor, Department of Orthodontics and Dental Research Institute, Seoul National University School of Dentistry, 101 Daehakro, JongroGu, Seoul 03080, Korea (e-mail: nonext@snu.ac.kr) Accepted: July 2021. Submitted: January 2021. Published Online: October 4, 2021 Ó 0000 by The EH Angle Education and Research Foundation, Inc. DOI: 10.2319/010121-1.1 1 Angle Orthodontist, Vol 00, No 00, 0000 Downloaded from http://meridian.allenpress.com/angle-orthodontist/article-pdf/doi/10.2319/010121-1.1/2916964/10.2319_010121-1.1.pdf by Lebanon user on 10 October 2021 Min-Gyu Kima; Jun-Ho Moona; Hye-Won Hwangb; Sung Joo Choa; Richard E. Donatellic; Shin-Jae Leed 2 MATERIALS AND METHODS The subjects of this study consisted of 268 children who visited the Department of Orthodontics, Seoul National University Dental Hospital, Seoul, Korea. Although they had sought orthodontic treatment, some of them hesitated to begin treatment immediately and deferred their treatment for timing or monetary reasons. Others were diagnosed to be enlisted as orthognathic surgery patients, and their treatment plans were to observe growth without any orthodontic/orthognathic intervention at the first visit. For all subjects of this study, at least two serial lateral cephalometric images existed: the one taken at the first visit (T1) and another after the observation period (T2). The mean ages at T1 and T2 were 11.1 and 13.7 years, respectively. The mean time elapsed between the two visits was 2.7 years. The characteristics of the Angle Orthodontist, Vol 00, No 00, 0000 Table 1. Descriptive Summary of Study Dataa Study Variables N (%) Total 268 (100) Female 145 (54.0) Male 123 (46.0) Cephalometric images taken at T1 and T2 536 (100) Age at T1 (years) 268 (50.0) Age at T2 (years) 268 (50.0) Time elapsed between the two serial images (T2 – T1, years) Skeletal Classification 268 (100) Class I 70 (26.0) Class II 107 (39.9) Class III 91 (34.1) a Mean SD 11.1 13.7 2.7 3.0 3.8 2.0 SD indicates standard deviation. subjects included in the present study are listed in Table 1. The institutional review board for the protection of human subjects of the Seoul National University Dental Hospital reviewed and approved the research protocol (ERI 19007). For each T1 and T2 image, cephalometric tracing, landmark identification, and labeling were manually performed by examiner 1 (SJL). The T2 image was superimposed on the T1 image by three superimposition methods: Björk’s structural method, the conventional SN superimposition method, and the automatic superimposition method based on multiple landmarks (ML). The experimental design is summarized in Figure 1. Three Superimposition Methods Superimposition by Björk’s structural method was assisted by a custom made user-interface implemented by the Python programming language (Python Software Foundation, Wilmington, Delaware, USA). On the user interface, the transparency of each image was freely adjustable to facilitate the superimposition of cranial base structures. Examiner 2 (MGK) manually translated and rotated the second image at T2 on the first image at T1 so that the stable cranial base structures overlapped as much as possible. To evaluate the reproducibility of manual superimposition by Björk’s structural method using the user-interface, 30 subjects were randomly selected and the superimposition procedure was repeated by the same examiner at a 3-month interval. As a result, the mean intra-examiner differences for the selected landmarks were 0.84 6 0.66 mm at Anterior Nasal Spine (ANS), 0.87 6 0.67 mm at Point A, 1.32 6 0.99 mm at Point B, and 1.44 6 1.97 mm at Pogonion. Both of the SN and ML methods were implemented based on the x, y coordinates of the cranial base landmarks. Unlike the conventional SN superimposi- Downloaded from http://meridian.allenpress.com/angle-orthodontist/article-pdf/doi/10.2319/010121-1.1/2916964/10.2319_010121-1.1.pdf by Lebanon user on 10 October 2021 cranial base structures and has been adopted and advocated by the American Board of Orthodontics. However, this superimposition method not only requires high-quality radiographs, but also demands time and effort in accurately identifying cranial base contours.16 Since Björk’s structural method requires line drawings of curved contours instead of just pinpointing certain landmarks, it is not compatible with the current computer environment. Therefore, for computer-aided superimpositions, the Sella-Nasion (SN) superimposition method has widely been applied for use in clinical practice.12,14,17–20 However, since Nasion is affected by growth and remodeling, the SN superimposition method that exclusively depends on entirely these two landmarks is likely to result in errors, especially when evaluating growth.21–23 To overcome the disadvantages of the traditional SN superimposition method, an automatic superimposition method that depends collectively upon six landmarks (Sella, Nasion, Porion, Orbitale, Basion, and Pterygoid) was proposed.15 This method is highly compatible with computer-aided cephalometrics and demonstrates more accurate results than the conventional SN superimposition method. However, the automatic method was tested on adult patients. Although it might be suitable for comparing posttreatment outcomes in non-growing patients, its application to growing patients has not yet been determined.15 With Björk’s structural method as a reference, the purpose of this study was to compare the superimposition results of the conventional SN superimposition method to the automated superimposition method on growing patients. The null hypothesis was that there would be no difference between the two superimposition methods in growing patients. KIM, MOON, HWANG, CHO, DONATELLI, LEE AUTOMATIC GROWTH SUPERIMPOSITION 3 tion method that is based only on two cranial base landmarks, Sella and Nasion, the ML superimposition method included four additional landmarks: Porion, Orbitale, Basion, and Pterygoid. For each lateral cephalometric radiograph and its associated cranial base landmarks, the second tracing was location shifted and rotation transformed until the sum of squared Euclidean distance measures in the cranial base landmarks between the first and second images were minimized, while Sella remained in an identical location.15 Comparisons Among Superimposition Methods In the present study, Björk’s structural method, which is dependent upon stable cranial base structures, was considered the reference for comparing the superimposition accuracy between the SN superimposition and the ML superimposition methods (Figure 2). To compare the accuracy between the SN and ML superimposition methods, four cephalometric landmarks (ANS, Point A, Point B, and Pogonion) were tested. These landmarks were selected since they Angle Orthodontist, Vol 00, No 0, 0000 Downloaded from http://meridian.allenpress.com/angle-orthodontist/article-pdf/doi/10.2319/010121-1.1/2916964/10.2319_010121-1.1.pdf by Lebanon user on 10 October 2021 Figure 1. Study flow chart. 4 KIM, MOON, HWANG, CHO, DONATELLI, LEE were known to best reflect the subjects’ characteristics and best recognize the variability of the maxilla and the mandible.14 Using each superimposition method, T2 image points were designated as P2Björk, P2SN, and P2ML. To evaluate the accuracy of the two superimposition methods, the Euclidean distances between P2Björk and P2SN, and P2Björk and P2ML, were calculated in millimeters. Whichever value was closer to zero indicates which method (SN or ML) could be regarded as a more accurate superimposition method for growing patients (Figure 2). Statistical Analysis Paired t-test was applied to compare the differences between the conventional SN and ML superimposition methods. Multiple linear regression analysis was performed to identify factors that could affect the accuracy of the superimpositions. In the regression model, the distance from Björk’s method of each reference point was set as the dependent variable. Angle Orthodontist, Vol 00, No 00, 0000 The factors that were assumed to affect the accuracy of superimposition in growing patients were chosen as independent variables: SN vs ML superimposition methods, cephalometric landmarks, age at T1, and the time elapsed between the two consecutive images (T1 to T2). Data preparation and all the statistical analyses were performed using Language R.24 The significance level was set at P , .05. RESULTS The difference between the SN and ML superimposition methods for ANS, Point A, Point B, and Pogonion are summarized in Table 2. For every landmark, there was a statistically significant difference between the SN and ML superimposition methods. The ML superimposition method demonstrated smaller differences from Björk’s method than did the conventional SN method. The differences increased in order from ANS, Point A, Point B, to Pogonion. Downloaded from http://meridian.allenpress.com/angle-orthodontist/article-pdf/doi/10.2319/010121-1.1/2916964/10.2319_010121-1.1.pdf by Lebanon user on 10 October 2021 Figure 2. T1 (at the first visit) and T2 (at the second visit) tracings superimposed by three different superimposition methods. The figure illustrates focusing on the specific landmark of Pogonion (Pog). For a given cephalometric landmark P, P2Björk signifies the position of P in the second tracing oriented by Björk’s structural method; P2SN by the SN superimposition method; and P2ML by the ML superimposition method. P2ML - P2Björk indicates the difference between the ML and Björk’s structural method; P2SN - P2Björk indicates the difference between the SN and Björk’s structural method. AUTOMATIC GROWTH SUPERIMPOSITION 5 Table 2. Comparisons of the Differences Between the Superimposition Methodsa,b ML method, P2Björk - P2ML Mean Mean 1.53 1.57 2.19 2.39 SD 1.45 1.47 1.97 2.15 1.36 1.40 1.94 2.12 SD 1.29 1.31 1.79 1.94 Mean Difference 0.17 0.17 0.24 0.27 P Valuec .0034 .0033 .0053 .0062 a For each landmark P (ANS, Point A, Point B, Pogonion), the position of P in the T2 image oriented by each superimposition method was denoted by P2Björk, P2SN, and P2ML, for Björk’s, the SN, and the ML superimposition methods, respectively. b SD indicates standard deviation. c Results from the paired t-test. Results of the multiple linear regression analysis indicated that the superimposition method, the cephalometric landmarks, the age at T1, and the time elapsed between the two serial images were statistically significant factors when determining the differences among the superimpositions. For example, the SN method had a greater difference than the ML method. Pogonion, the farthest designated point from the cranial base, had the greatest difference among the cephalometric landmarks tested. The older the T1 age, the more the superimposition difference decreased. The greater elapsed time between T2 and T1 also resulted in the greater difference among the cephalometric landmarks tested (Table 3). Figure 3 demonstrates an example of the results of all the superimposition methods being applied to subject images. Just from casual observation, it is evident that the ML method more closely followed Björk’s structural method. DISCUSSION The purpose of this study was to compare the widely used conventional SN superimposition method with the ML superimposition method on growing patients. The reference superimposition method was Björk’s structural method. The null hypothesis was that there would be no difference in the accuracy of the two superimposition methods. To identify variables that may affect the accuracy of a superimposition method, multiple linear regression analysis was used. The results of this study indicated that there was a statistically significant difference between the two superimposition methods. The ML method was found to be 0.17 mm, 0.17 mm, 0.24 mm, and 0.27 mm more accurate than the SN method at ANS, Point A, Point B, and Pogonion, respectively. The difference between the two methods was an average of 0.21 mm, indicating that the ML method was 0.21 mm closer to Björk’s structural superimposition method used as a reference. Howev- Study Variables b SN vs ML superimposition method 0.21 (reference, ML) Cephalometric landmarks (reference, ANS) Point A 0.04 Point B 0.62 Pogonion 0.81 Age at T1 (1-year increments) -0.08 T2 – T1 (1-year increments) 0.22 SE(b) P Value 0.07 .0025 0.10 0.10 0.10 0.01 0.03 .7028 ,.0001 ,.0001 ,.0001 ,.0001 a ANS indicates anterior nasal spine; b, regression coefficients; ML, automated superimposition method based on multiple landmarks; SE, standard error; SN, Sella-Nasion superimposition method. er, this might not be a clinically significant result. Several studies claimed that a difference of more than 1mm should be considered clinically significant.2,25 The major advantage of the ML method was that it could be applied automatically and be just as, if not more, reliable than the laborious, manual Björk’s structural superimposition method. The location of each anatomical landmark, the age at the first visit, and the time elapsed between the two consecutive images were found to affect the differences between the superimposition methods. The difference between superimposition methods tended to increase as the landmarks were positioned lower in the face (Tables 2 and 3). Since cranial base structures are used as a reference when superimposing lateral cephalometric images, differences between superimposition methods would increase as the landmarks were more distant from the cranial base. Therefore, ANS and Point A, which are relatively close to the cranial base, produced more accurate superimposition results than Point B and Pogonion. In other words, when analyzing growth, superimposition is more likely to differ from the reference Björk’s structural method in the mandible compared to the maxilla. In addition, regression coefficients obtained were -0.08 for age at T1 and 0.22 for the time elapsed between the two serial images (T2-T1), which indicated that the younger the first image was taken and the longer the time interval between the first and second images, the greater the difference between the two superimposition methods. The increase in difference between superimposition methods may have been related to growth of the cranial base. As growth occurs, there naturally would be changes in the cranial base structures used as references in superimpositions. The conventional SN method might not properly reflect the changes caused by growth over time, resulting in greater differences Angle Orthodontist, Vol 00, No 0, 0000 Downloaded from http://meridian.allenpress.com/angle-orthodontist/article-pdf/doi/10.2319/010121-1.1/2916964/10.2319_010121-1.1.pdf by Lebanon user on 10 October 2021 ANS Point A Point B Pogonion SN method, P2Björk - P2SN Table 3. Summary of Multiple Linear Regression Analysis of the Differences in the Superimpositions. Model Included Factors Such as SN vs ML, Cephalometric Landmarks, Age at T1, and Time Elapsed Between the Two Serial Images (T2 – T1)a 6 KIM, MOON, HWANG, CHO, DONATELLI, LEE from Björk’s structural method. The anterior cranial base consists of structures that complete their growth at different times. Presphenoidal regions were reported to nearly complete growth at seven years of age; ethmoid regions were reported nearly complete at four years of age. However, the frontal segment and Sella Turcica have been reported to continue to remodel until early adulthood. Sella is constantly remodeling and moves backward and downward; Nasion moves forward due to the expansion of the frontal sinus.21 Even anteroposterior length of the maxillary complex might be associated with the anterior cranial base.26 Therefore, the SN superimposition method using Sella and Nasion as landmarks that move during the growth phase may be less reliable and result in faulty judgment. The ML superimposition method may have several advantages over the conventional SN superimposition method and even Björk’s structural method. First, it is capable of reducing the overdependence on Sella and Nasion points. From previous studies, superimposition errors could occur from rotation and translation Angle Orthodontist, Vol 00, No 00, 0000 mistakes. Typical superimposition errors are mainly caused by rotation errors rather than translation errors.27 The ML method fixed Sella at the same location and rotated the T2 image until the sum of the distances of the remaining five landmarks were minimized. Therefore, superimposition errors were reduced because of a greater degree of freedom to rotate around Sella was permitted, unlike the SN superimposition method. Second, the ML superimposition method is compatible with computer-aided cephalometrics, allowing full automation. By automatically identifying landmarks as well as, or better than, a human, then using multiple landmarks to create accurate lateral cephalograph tracings,10,13 then automatically superimposing these lateral cephalographs with comparable or better accuracy of growth changes, the ML method demonstrated its value to orthodontics. CONCLUSIONS The null hypothesis that there would be no difference in the accuracy between the SN and ML superimposition methods on growing subjects is rejected. Downloaded from http://meridian.allenpress.com/angle-orthodontist/article-pdf/doi/10.2319/010121-1.1/2916964/10.2319_010121-1.1.pdf by Lebanon user on 10 October 2021 Figure 3. Real patient application. The growth observation periods for these boys were 3 years, 2 months; and 3 years, 6 months, respectively. AUTOMATIC GROWTH SUPERIMPOSITION ACKNOWLEDGMENT This study was partly supported by grant 05-2020-0021 from the Seoul National University Dental Hospital Research Fund. REFERENCES 1. Gu Y, McNamara Jr JA. Cephalometric superimpositions: a comparison of anatomical and metallic implant methods. Angle Orthod. 2008;78:967–976. 2. Huja S, Grubaugh E, Rummel A, Fields H, Beck F. Comparison of hand-traced and computer-based cephalometric superimpositions. Angle Orthod. 2009;79:428–435. 3. 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Testing a better method of predicting postsurgery soft tissue response in Class II patients: a prospective study and validity assessment. Angle Orthod. 2015;85:597–603. 21. Afrand M, Ling CP, Khosrotehrani S, Flores-Mir C, Lagravère-Vich MO. Anterior cranial-base time-related changes: a systematic review. Am J Orthod Dentofacial Orthop. 2014;146:21–32.e6. 22. Arat M, Köklü A, Özdiler E, Rübendüz M, Erdogan B. Craniofacial growth and skeletal maturation: a mixed longitudinal study. Eur J Orthod. 2001;23:355–361. 23. Arat ZM, Rübendüz M, Arman Akgül A. The displacement of craniofacial reference landmarks during puberty: a comparison of three superimposition methods. Angle Orthod. 2003; 73:374–380. 24. R Core Team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2021. 25. Ghafari J, Engel FE, Laster LL. Cephalometric superimposition on the cranial base: a review and a comparison of four methods. Am J Orthod Dentofacial Orthop. 1987;91:403– 413. 26. Savoldi F, Massetti F, Tsoi JKH, et al. Anteroposterior length of the maxillary complex and its relationship with the anterior cranial base. Angle Orthod. 2021;91:88–97. 27. Baumrind S, Miller D, Molthen R. The reliability of head film measurements: 3. Tracing superimposition. Am J Orthod. 1976;70:617–644. Angle Orthodontist, Vol 00, No 0, 0000 Downloaded from http://meridian.allenpress.com/angle-orthodontist/article-pdf/doi/10.2319/010121-1.1/2916964/10.2319_010121-1.1.pdf by Lebanon user on 10 October 2021 From the results of this study in growing patients, the automated superimposition method based on the multiple landmarks seems to be more similar to Björk’s structural method than the SN superimposition method, but only marginally so. Despite the small differences, the major advantage of the ML method is likely to be that it can be applied automatically and may be just as reliable as manual superimposition methods. 7