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SPECT bone scintigraphy for the assessment of condylar growth activity in mandibular asymmetry: is it accurate?
YIJOM-3793; No of Pages 10
Int. J. Oral Maxillofac. Surg. 2017; xxx: xxx–xxx http://dx.doi.org/10.1016/j.ijom.2017.09.008, available online at http://www.sciencedirect.com
Clinical Paper Orthognathic Surgery
SPECT bone scintigraphy for the assessment of condylar growth activity in mandibular asymmetry: is it accurate?
B. H. Chan, Y. Y. Leung Oral and Maxillofacial Surgery, Faculty of Dentistry, The University of Hong Kong, Prince Philip Dental Hospital, Sai Ying Pun, Hong Kong
B. H. Chan, Y. Y. Leung: SPECT bone scintigraphy for the assessment of condylar growth activity in mandibular asymmetry: is it accurate?. Int. J. Oral Maxillofac. Surg. 2017; xxx: xxx–xxx. ã 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Abstract. The comparison of serial radiographs and clinical photographs is considered the current accepted standard for the diagnosis of active condylar hyperplasia in patients with facial asymmetry. Single photon emission computed tomography (SPECT) has recently been proposed as an alternative method. SPECT can be interpreted using three reported methods absolute difference in uptake, uptake ratio, and relative uptake. SPECT findings were compared to those from serial comparisons of radiographs and clinical photographs taken at the time of SPECT and a year later; the sensitivities and specificities were determined. Two hundred patient scans were evaluated. Thirty-four patients showed active growth on serial growth assessment. On comparison with serial growth assessment, the sensitivity and specificity of the three methods ranged between 32.4% and 67.6%, and 36.1% and 78.3%, respectively. Analysis using receiver operating characteristic (ROC) curves revealed area under the curve (AUC) values of <0.58. The average age (mean standard deviation) of patients with active growth was 18.6 2.8 years, and average growth in the anteroposterior, vertical, and transverse directions was 0.94 0.91 mm, 0.88 0.86 mm, and 1.4 0.66 mm, respectively. With such low sensitivity and specificity values, it is not justifiable to use SPECT in place of serial growth assessment for the determination of condylar growth status.
Accepted for publication
Facial asymmetry is an aesthetically and functionally unsatisfactory condition that may arise from a number of causes, such as joint resorption, infection-related growth disturbances, and neoplastic changes, among others1–3. Amongst these
ence, developmental causes, and heredity or genetics, have been suggested1. Progressive condylar growth eventually results in alterations to the dimensions of the condylar neck, ramus, and body of the mandible6. A gradual progression
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causes, condylar hyperplasia is a pathological condition that presents as a progressive and excessive growth of one or both mandibular condyles3–5. It has an unknown aetiology, although possible causes including trauma, functional influ-
Key words: condylar hyperplasia; SPECT bone scintigraphy; serial radiograph tracing; sensitivity; specificity.
ã 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Chan BH, Leung YY. SPECT bone scintigraphy for the assessment of condylar growth activity in mandibular asymmetry: is it accurate?, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.09.008
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of the asymmetry over a long period of time of several years has been observed to occur, but it may also occur within a short time span of weeks to months. The condition may present in early childhood at 6–7 years of age, or at any time during the patient’s adolescence growth period, and even after the cessation of skeletal bone growth7,8. This makes the timing of treatment commencement crucial and possibly difficult to predict. The incidence has been reported to be higher in females, with more than 64% of those presenting with the condition being female according to a systematic review by Raijmakers et al.9; however, other studies have not shown this sex difference10. Condylar hyperplasia was first described by Robert Adams in 1836 and then, amongst others, by George Humphry in 1856, who reported dentofacial deformity with resultant chin deviation as the characteristics of this condition. This is also correlated to dental malocclusion with a non-incident dental midline and unilateral crossbite or open bite3. In 1986, Obwegeser and Makek classified condylar hyperplasia into two main types, namely hemimandibular hyperplasia and hemimandibular elongation11. These presentations may occur individually or in combination, to result in the eventual dentofacial asymmetry. Numerous other classifications have been suggested1,12, illustrating the difficulties faced in describing this condition. While the condition is generally selflimiting, the extent of the gross asymmetry is dependent on the extent of condylar hyperplastic growth activity10,13. The condition may contribute to functional and aesthetic deficits, which may result in a negative impact on the patient’s quality of life and function. A study conducted by Naini et al. showed that the patient’s desire to seek surgical treatment for the correction of this condition was correlated with the severity of the asymmetry14. It was also found that a small 5 mm deviation is noticeable to the layperson. The use of serial observation of growth and serial cephalometric and dental model comparisons is considered as the current accepted standard for the determination of condylar growth status4,15,16. This technique requires a minimum period of time between observations (usually 6 months to 1 year) in order to determine the status, which is time-consuming. The findings from the comparisons can only reveal past growth history, and they do not allow the future condylar growth potential to be determined15,17. Bone scintigraphy has been used to aid in the determination of bone growth activ-
ity since the early 1980s. The initial method of scintigraphy involved capture in planar view, with the amount of uptake by the condyles correlated to the T4 spine. This required separate imaging of the T4 spine, as it could not be captured within the condylar view. In recent years, single photon emission computed tomography (SPECT) has been proposed as a more accurate and reliable form of bone scintigraphy, as it allows the three-dimensional evaluation of condylar uptake. The clivus bone, which is situated at the skull base, is considered to be metabolically stable after the fusion of the spheno-occipital synchondrosis. It is used as a reference point for comparison of uptake values in the condyles15,18,19. As the clivus is also captured along with the condyles during the scan, there is no need for two separate images to be captured. However, it has been reported that bone scans are sensitive but not specific, and that conditions affecting the joints, such as healing bone (post-surgery or trauma), joint infection, inflammation (arthritis), and neoplastic changes, can result in a positive scan value20–23. The reported sensitivity and specificity of SPECT scans has varied amongst studies. Sensitivity values of between 78% and 98%, with a pooled sensitivity of 90%, and specificity values of between 60% and 95%, have been reported13,19,24. In the study by Saridin et al., the optimal cutoff value for comparison between the affected and contralateral condyles was determined to be 55%, and the reported sensitivity and specificity were around 88%19. Another study suggested that the optimal cut-off is 56%, with sensitivity of 93% and specificity of 96%, based on the area under the receiver operating characteristics curve4. However, the results from these previous studies supporting SPECT scans were obtained by deriving the outcomes from analyzing patients with condylar hyperplasia at a single clinical time point only, and there was no additional external validation or comparison of the results to an accepted standard. Hence, there is a knowledge gap regarding the true sensitivity and specificity of SPECT as a diagnostic test. As it appears that there have been no previous studies comparing SPECT against a reliable standard, and with the reported wide range of sensitivity and specificity values, it remains necessary to measure the accuracy and reliability of SPECT. Such an evaluation is also required to justify exposing patients to the additional radiation (4 mSv per exposure) of the SPECT scan. The aims of this study were to determine the sensitivity and specificity of
SPECT bone scintigraphy when used in patients with facial asymmetry arising from condylar hyperplasia, and to identify general patterns of condylar growth in the study population according to sex and age groups. Materials and methods
Patients with mandibular asymmetry caused by condylar hyperplasia, who presented to the Discipline of Oral and Maxillofacial Surgery, Faculty of Dentistry, The University of Hong Kong between January 2011 and July 2013, and who underwent SPECT bone scintigraphy for pre-treatment assessment, were recruited. Patients who fulfilled the following criteria were included: (1) mandibular asymmetry as a result of condylar hyperplasia; (2) availability of lateral and postero-anterior cephalometric radiographs taken around the time of SPECT bone scintigraphy and 1 year afterwards. Patients with the following conditions were excluded: (1) history of temporomandibular joint surgery; (2) presence of a neoplastic pathology of the temporomandibular joint, e.g. osteochondroma; (3) presence of systemic diseases that could potentially affect the temporomandibular joint, e.g. autoimmune conditions; (4) congenital conditions and syndromes that are associated with facial asymmetry, e.g. hemifacial microsomia. SPECT bone scintigraphy and analysis
SPECT scans were performed 2–4 h after the intravenous administration of 20–25 mCi technetium 99m-methylene diphosphonate (99mTc-MDP). A region of interest (ROI) of 16 pixels 3 slices was drawn over both condylar heads. The individual condylar counts within the ROIs were calculated and expressed as an average against the clivus bone count. The determination of active condylar growth from the condylar counts was assessed using three reported methods. The first was the absolute difference in uptake (i.e. active inactive)25, in which the condylar count of the inactive condyle was subtracted from that of the active condyle. A difference in scan values of 0.34 0.40 (mean standard deviation (SD)) between the active and inactive condyles was considered to indicate active growth. The second method was the uptake ratio, i.e. (active/inactive) 100%5,16,26, in which the ratio of the active condylar count against the inactive condylar count was calculated as a percentage. Growth was considered to be
Please cite this article in press as: Chan BH, Leung YY. SPECT bone scintigraphy for the assessment of condylar growth activity in mandibular asymmetry: is it accurate?, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.09.008
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Diagnostic accuracy of SPECT active if the percentage was more than 10%, and vice versa. The third method was the relative uptake (condylar activity percentage), i.e. (active/(active + inactive)) 100%5,10,16,19,27, in which the active condylar count over the total condylar count was calculated as a percentage. Growth was considered to be active if the uptake value percentage was 55% or more. Serial radiographic tracings and growth assessment
Lateral and postero-anterior (PA) cephalometric radiographs (magnification 1.23, Orthoralix 9200 X-ray system; Gendex, Hatfield, Pennsylvania, USA) were traced using an overlay ortho/ trace film 0.003 matte acetate for the baseline radiographs taken at the time of the SPECT scan. The lateral and PA
cephalometric radiographs that were taken 1 year after were then traced and compared to the baseline radiographs of the same patient. Stable anatomical landmarks on the radiographs were traced. For the lateral cephalometric radiographs, the base of the skull, orbital rims, and the condylar head were marked as the reference landmarks. To determine the presence of growth, the posterior and inferior borders of the mandible and the chin region were traced. Any visible growth in the vertical and anteroposterior direction was detected and measured from the menton and pogonion, respectively, with a clear plastic ruler with 0.5-mm-interval markings (Fig. 1). For the PA cephalometric radiographs, a horizontal reference plane (x-axis) was drawn between the right and left lateral orbitale (LO) landmarks. A vertical line (y-axis) was dropped perpendicular to the
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horizontal plane using the crista galli as the reference point, towards the inferior border of the anterior mandible. The distance on the x-axis from menton to the vertical line was measured and compared to detect any changes in the transverse direction (Fig. 2). Additional comparisons were performed for patients with clinical photographs available that were taken at the time of the SPECT scan and a year later. Intraoral photographs of the same patient taken at a 1-year interval were also compared. The frontal, profile, and intraoral photographs were overlapped using Dolphin Imaging software (version 11.9.07.24 Premium; Dolphin Imaging and Management Solutions, Chatsworth, CA, USA) for correlation with the findings from the serial radiographic tracings (Fig. 3). Growth was considered to be active if any of the three assessments (lateral ceph-
Fig. 1. Tracing of a lateral cephalometric radiograph.
Please cite this article in press as: Chan BH, Leung YY. SPECT bone scintigraphy for the assessment of condylar growth activity in mandibular asymmetry: is it accurate?, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.09.008
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Chan and Leung against the findings of the serial growth assessment. Receiver operating characteristics (ROC) curves were also plotted to compare the different methods, and the method that had a curve closest to the upper left quadrant had the best diagnostic ability. The area under the curve (AUC) was also calculated for each method.
Results
Fig. 2. Comparison of transverse growth on postero-anterior cephalometric radiographs. LO, lateral orbitale; CG, crista galli; Me, menton.
alometric serial tracing, PA cephalometric serial tracing, and clinical photographic changes) showed any changes. If none of these assessments showed any changes across the 1-year interval, the subject was considered to be inactive for growth. Comparison of SPECT bone scintigraphy and serial growth assessment
The results from SPECT bone scintigraphy were compared to the growth status results determined in the serial growth assessment. For each patient, the results for the three SPECT analysis methods were compared against the findings of the serial growth assessment. The numbers of true-positives (where a positive SPECT finding corresponded with a positive serial growth status) and true-negatives (where a negative SPECT finding corresponded with a negative serial growth status) were calculated. The sensitivity was calculated as the percentage of true-positives over the total positive results for each SPECT analysis method, and the specificity was cal-
culated as the percentage of true-negatives over the total negative results. Statistical analysis
The statistical analysis was performed using IBM SPSS Statistics version 23.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics, including the mean SD, were used to describe the demographic background of the samples. The mean movements of menton and pogonion for patients with active growth were also obtained. Significant differences in growth between sex and age groups were determined using the parametric t-test for data following a normal distribution, and the nonparametric Mann–Whitney U-test for data that did not. Significant differences in proportions of patients with active growth according to sex and age groups were calculated with the Pearson x2 test. A 5% level of significance was applied. The sensitivity and specificity of the three assessment methods were calculated
A total of 265 patients were initially recruited into the study, of whom 65 were excluded based on the exclusion criteria. Of the 200 patients included, 82 (41%) were male and 118 (59%) were female, giving a male to female ratio of approximately 1:1.43. The mean age of the patients was 21.0 4.3 years; the mean age of male patients was 21.7 4.0 years and of female patients was 20.6 4.4 years. The general demographic data of the 200 patients are presented in Table 1. Serial tracings of the scans of 200 patients were analyzed, and 34 patients (17%) were found to have active growth in at least one of the three measured dimensions; of these patients, 21 (61.8%) were female and 13 (38.2%) were male. The SPECT scans were analyzed and the findings are presented in Table 2. With regard to the absolute difference in uptake measurement, 47 patients were found to have active growth. When the uptake ratio was calculated, 129 patients were found to have active growth, and when relative uptake was measured, 68 patients had active growth. There were statistically significant differences (P < 0.001) between the proportions of active scan results between the three methods of SPECT scan measurement, indicating poor validity amongst them. The findings of the SPECT scans were compared to those from serial growth assessment, as illustrated in Table 3. Each SPECT analysis method was compared against the serial growth assessment, and the numbers of true active and inactive findings were determined. The absolute difference in uptake measurement identified 11 true active patients, which was the lowest result among the three methods. The uptake ratio identified 23 true active patients and the relative uptake identified 14 true active patients. When the true inactive findings were compared, the uptake ratio identified the lowest number of true inactive findings with 60 patients; the absolute difference in uptake identified 130 true inactive patients and relative uptake identified 112 true inactive patients.
Please cite this article in press as: Chan BH, Leung YY. SPECT bone scintigraphy for the assessment of condylar growth activity in mandibular asymmetry: is it accurate?, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.09.008
YIJOM-3793; No of Pages 10
Diagnostic accuracy of SPECT
Fig. 3. Comparison of clinical photographs. (a) Frontal photographs showing vertical and transverse growth. (b) Lateral photographs showing vertical growth at menton. (c) Frontal intraoral photographs of the dentition, using the upper anterior teeth as reference; growth is noted from the difference in lower anterior teeth positions.
The sensitivity and specificity of the three methods are presented in Table 4. The absolute difference in uptake yielded the lowest sensitivity at 32.4% and the uptake ratio had the highest sensitivity at 67.6%; the sensitivity of relative uptake was 41.2%. With regard to specificity, the uptake ratio had the lowest specificity at 36.1%, relative uptake had a specificity of
67.5%, and the absolute difference in uptake had the highest specificity at 78.3%. The sensitivity and specificity of all three methods are considered to be low. The ROC curves for the three methods are presented in Fig. 4. All three methods had low AUC values of less than 0.58, indicating that the ability of the three SPECT analysis methods to detect growth
Table 1. Patient demographic characteristics. Number (%) Male Female Total
82 (41) 118 (59) 200
SD, standard deviation.
Age (years), mean SD 21.7 4.0 20.6 4.4 21.0 4.3
Active growth, number (%) 13 (38.2) 21 (61.8) 34
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was only slightly more than random chance. An AUC of 0.50 is equivalent to random chance. Based on the findings of the primary outcome of sensitivity and specificity, and supported by the AUC calculations, the three SPECT analysis methods proposed are not suitable to be used as a diagnostic tool for condylar hyperplasia. Further analyses of the findings from the serial growth assessment were performed; the results are presented in Table 5. Thirty-four of the total 200 patients (17%) had active growth. The average age of the patients with true active growth as determined from the serial growth assessment was 18.6 2.8 years. The average age of the male patients with active growth was 19.2 2.9 years, and the average age of the female patients with active growth was 18.3 2.7 years. There was no statistically significant difference in the proportion of patients with active growth between the male and female patients (P = 0.719). Further stratification of the sample population by age groups was done (Table 6). Of the 34 patients with active growth, 10 were younger than 17 years old. Eleven patients were aged 17 to <19 years, seven were between 19 and <21 years old, and six were 21 years old. Patients below the age of 19 years accounted for more than half (61.7%) of the patients with active growth. The age group of <17 years had the highest percentage of patients with active growth (47.6%) when compared to the other age groups; correspondingly, the age group 21 years had the lowest percentage of patients with active growth (7.6%). A general trend was observed, in which approximately half of the patients below 17 years of age had active growth. This percentage then further halved in each subsequent age group, with 7.6% of patients with active growth in the 21 years age group (Fig. 5). There were significant differences in the proportions of patients with active growth in those <17 years of age compared to the other three age groups. A significant difference was also found between the 17 to <19 years group and the 21 years group (P = 0.021). There was no other difference in the proportions of patients with active growth for the other comparisons. The amounts of growth in the anteroposterior, vertical, and transverse directions in the 34 patients with active growth were recorded; the results are presented according to sex in Table 7. The average growth was 0.94 0.91 mm in the anteroposterior direction, 0.88 0.86 mm in the vertical direction, and 1.4 0.66 mm
Please cite this article in press as: Chan BH, Leung YY. SPECT bone scintigraphy for the assessment of condylar growth activity in mandibular asymmetry: is it accurate?, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.09.008
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Table 2. Analysis of SPECT scans. Method
Number (%)
Growth status from serial growth assessment Active Inactive
34 (17) 166 (83)
Absolute difference in uptake Active Inactive
47 (23.5) 153 (76.5)
Uptake ratio Active Inactive
129 (64.5) 71 (35.5)
Relative uptake Active Inactive
68 (34) 132 (66)
Differences in proportion of active counts P < 0.001a,* P < 0.001a,* P < 0.001a,*
Absolute difference versus uptake ratio Absolute difference versus relative uptake Uptake ratio versus relative uptake * a
Significant difference (P < 0.05). Pearson x2 test.
Table 3. Comparison of SPECT scans and serial growth assessment. Serial growth assessment SPECT assessment
Active
Inactive
Total
Absolute difference in uptake
Active Inactive Total
11 23 34
36 130 166
47 153 200
Uptake ratio
Active Inactive Total
23 11 34
106 60 166
129 71 200
Relative uptake
Active Inactive Total
14 20 34
54 112 166
68 132 200
in the transverse direction. For the male patients, the average anteroposterior, vertical, and transverse growth was 1.3 1.1 mm, 1.2 1.1 mm, and 1.3 0.43 mm, respectively. For the female patients, the average anteroposterior change was 0.69 0.68 mm, vertical change was 0.69 0.62 mm, and transverse change was 1.5 0.78 mm. There was a significant difference in
the amount of anteroposterior growth between male and female patients (P = 0.039), with male patients exhibiting significantly more anteroposterior growth than female patients. Analysis of the vertical and transverse growth between the sexes did not reveal any significant difference (P = 0.232 and P = 0.753, respectively).
A further analysis of the amount of growth exhibited by true active growth patients was performed by stratifying the patients into the age ranges. The findings are presented in Table 8. Patients <19 years of age appeared to have higher yearly growth amounts as compared to patients aged 19 years. However, there was no significant difference between the mean anteroposterior (P = 0.169), vertical (P = 0.552), and transverse (P = 0.193) growth between the two age groups. Discussion
The key findings of this study were (1) the sensitivity of the three analysis methods of SPECT bone scintigraphy to determine condylar growth ranged between 32.4% and 67.6%, and the specificity between 36.1% and 78.3%; and (2) the AUC of the ROC curves was low at <0.58. Both key findings show that SPECT scans were poor for determining condylar growth status. The proportions of patients with active condylar growth in the age groups <17 years, 17 to <19 years, 19 to <21 years, and 21 years were 47.6%, 21.6%, 14.3%, and 7.6%, respectively. The treatment of patients with condylar hyperplasia is determined by the progression of the individual’s condylar growth. There are advantages and disadvantages to both commencing treatment earlier and adopting a watch-and-wait approach in the management of such patients. The condition tends to present during the patient’s adolescence period and may continue even after the cessation of skeletal bone growth. This gradual dentofacial asymmetry and its attendant dental malocclusion will no doubt result in some negative impact on the patient’s selfimage and confidence. The patients in this study presented with the condition at a young age – at an average of 21.0 4.3 years. This is in line with the findings reported by other
Table 5. Serial growth assessment. Table 4. Sensitivity and specificity of SPECT methods. Number (%) Absolute difference in uptake True-positive (sensitivity) True-negative (specificity)
11 (32.4) 130 (78.3)
Uptake ratio True-positive (sensitivity) True-negative (specificity)
23 (67.6) 60 (36.1)
Relative uptake True-positive (sensitivity) True-negative (specificity)
14 (41.2) 112 (67.5)
Factor
Number (%)
Growth status Active Inactive
34 (17) 166 (83)
Patients with active growth Male Female Difference in proportion of active growth between the sexes Mean age of patients with active growth, mean SD Total: 18.6 2.8 years Male: 19.2 2.9 years Female: 18.3 2.7 years
13 (38.2) 21 (61.8) P = 0.719a
SD, standard deviation. a Pearson x2 test.
Please cite this article in press as: Chan BH, Leung YY. SPECT bone scintigraphy for the assessment of condylar growth activity in mandibular asymmetry: is it accurate?, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.09.008
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Diagnostic accuracy of SPECT Table 6. Age group characteristics—serial growth assessment. Patients with active growth by age
Number (%)
<17 years Male Female
10 (29.4) 3 7
17 to <19 years Male Female
11 (32.4) 4 7
19 to <21 years Male Female
7 (20.6) 4 3
21 years Male Female
6 (17.6) 2 4
Proportion of patients with active growth in the age group
n/N (%)
<17 years 17 to <19 years 19 to <21 years 21 years
10/21 (47.6) 11/51 (21.6) 7/49 (14.3) 6/79 (7.6)
Differences in proportion of active counts <17 years <17 years <17 years 17 to <19 17 to <19 19 to <21 * a
vs. 17 to <19 years vs. 19 to <21 years vs. 21 years years vs. 19 to <21 years years vs. 21 years years vs. 21 years
P = 0.027a,* P = 0.003a,* P < 0.001a,* P = 0.343a P = 0.021a,* P = 0.223a
Significant difference (P < 0.05). Pearson x2 test.
authors7,8. The average age of females was generally younger than male patients by 1 year. This indicates that the condition is already present at an earlier age, as the majority of the patients were already found to have ceased growing when assessed (166 out of 200). The average age of the 34 patients with active growth
was younger, at 18.6 2.8 years. This is approximately 3 years lower than the overall average. Females with active growth also generally presented 1 year earlier than the male patients. This study also supports the higher incidence of the condition in females, as 59% of the scans were done for female
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patients. There were also more females within the active growth group, with 21 of the 34 patients (61.8%) being female. As determined in this study, the three SPECT methods had sensitivity between 32.4% and 67.6%, and specificity between 36.1% and 78.3%. Further analysis using ROC curves revealed AUC values of <0.58, indicating that the methods are no better than random chance. This was corroborated by statistically significant differences between the findings of the three methods, indicating poor validity and accuracy. Such low sensitivity and specificity values would result in a large percentage of false-positive and false-negative diagnoses, which would hinder and potentially negatively affect the treatment outcomes of patients. Two main treatment methods are currently proposed and practiced, namely high condylectomies and orthognathic surgery, or a combination of both6,28,29. These two methods are highly dependent on the clinician’s ability to accurately determine the patient’s growth status, as high condylectomies are used to arrest further growth of the affected condyle and orthognathic surgery should only be done after the cessation of growth. However, with such low sensitivity and specificity values, the use of SPECT scans would result in a number of false-positive and false-negative cases, which would lead to unnecessary over-treatment (high condylectomy or unnecessary growth reviews) for patients who are false-positive, or premature commencement of treatment (orthognathic surgery) for patients who are false-negative. Another
Fig. 4. Receiver operating characteristic (ROC) curves for SPECT. AUC, area under the curve; CI, confidence interval.
Please cite this article in press as: Chan BH, Leung YY. SPECT bone scintigraphy for the assessment of condylar growth activity in mandibular asymmetry: is it accurate?, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.09.008
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Fig. 5. Percentage of patients with active growth in each age group, as assessed using serial radiographs.
Table 7. Growth in the anteroposterior, vertical, and transverse direction according to sex; mean SD values. Growth in males Growth in females Average growth
Anteroposterior
Vertical
Transverse
1.3 1.1 mm 0.69 0.68 mm 0.94 0.91 mm
1.2 1.1 mm 0.69 0.62 mm 0.88 0.86 mm
1.3 0.43 mm 1.5 0.78 mm 1.4 0.66 mm
Differences according to sex Anteroposterior growth between males and females Vertical growth between males and females Transverse growth between males and females
P = 0.039a,* P = 0.232b P = 0.753b
SD, standard deviation. * Significant difference (P < 0.05). a Parametric t-test. b Non-parametric Mann–Whitney U-test performed for data that did not follow a normal distribution.
Table 8. Growth in the anteroposterior, vertical, and transverse direction according to age; mean SD values. <17 years 17 to <19 years 19 to <21 years 21 years
Anteroposterior
Vertical
Transverse
1.0 1.0 mm 1.2 1.0 mm 0.42 0.53 mm 0.83 0.6 mm
0.9 0.77 mm 0.86 0.67 mm 1.4 1.3 mm 0.33 0.4 mm
1.7 0.70 mm 1.0 0.38 mm 1.5 0.91 mm 1.7 0.4 mm
Difference according to age group Anteroposterior growth between <19 years and 19 years Vertical growth between <19 years and 19 years Transverse growth between <19 years and 19 years
P = 0.169a P = 0.552a P = 0.193a
SD, standard deviation. a Non-parametric Mann–Whitney U-test performed for data that did not follow a normal distribution.
major drawback of using SPECT is the need to expose patients to the highly radioactive 99mTc-MDP intravenous contrast during scans. The effective dose of a single SPECT scan is 4 mSv (4000 mSv), which is the equivalent of 200 chest X-rays (0.02 mSv)30, or 1.8 years of background radiation. In contrast, a panoramic radiograph has an effective dose of only 36 mSv, and a cone beam computed tomography (CBCT) scan only 432 mSv31,32. Wu et al. performed a study to predict the cancer risks from dental computed tomography and reported that the risk of cancer induction was higher if the exposed patient was younger, and also that females were at a higher risk than males32. This could be extrapolated to the use of 99mTcMDP for the purpose of determining condylar growth activity. SPECT scans for the purpose of condylar growth determination are typically done on younger patients, and with the higher prevalence of condylar hyperplasia in females, the majority of patients being exposed to radiation would be young females. A more worrying trend that was noted during this study was the taking of the raw condylar scan results at face value, which led to the diagnosis of a condyle with a higher count as active. Such diagnoses of active condylar growth were found to be prevalent during the reporting of the SPECT scans results. A small number of
Please cite this article in press as: Chan BH, Leung YY. SPECT bone scintigraphy for the assessment of condylar growth activity in mandibular asymmetry: is it accurate?, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.09.008
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Diagnostic accuracy of SPECT patients were also noted to have been subjected to repeated SPECT scans during their follow-up period, and it is the authors’ view that they were unnecessary. The main limitation of this study was the retrospective nature of the research. This limitation was overcome by the use of a well-developed treatment protocol and a detailed records system for patients who required skeletal growth monitoring in the unit. The findings of this study, however, suggest that it would be unethical to design a prospective study with similar aims and objectives, as the SPECT scans were proved to have low sensitivity and specificity. Also, with the high dosage of radiation exposure for relatively young individuals, it might be more valuable to design prospective studies to investigate three-dimensional mandibular growth patterns using advanced imaging techniques with a lower radiation exposure, such as CBCT. Other limitations of this study were that it was conducted at a single centre with a sample population comprising mainly patients of Asian descent. The study also only included patients with facial asymmetry caused by condylar hyperplasia. Therefore, the extrapolation of the findings from this study may not be wholly accurate when applied to a different geographical or racial group. Several considerations regarding the determination of condylar growth activity can be summarized from the findings of this study: (1) females were found to present with condylar hyperplasia at an earlier age, and correspondingly ceased their growth activity at an earlier age. (2) Male patients in general were found to present with condylar hyperplasia later than female patients and ceased their growth activity later. It would therefore be prudent not to commence definitive orthognathic surgery too early in male patients if condylar hyperplasia is noted. (3) Approximately half of the patients under the age of 17 years were found to have active condylar growth. This proportion halved in each subsequent age group, until only approximately 7% of patients 21 years of age were found to have active condylar growth. (4) The average change at the chin point over 1 year in the anteroposterior, vertical, and transverse dimensions was 0.94 mm, 0.88 mm, and 1.4 mm, respectively, with male patients growing almost twice as much as female patients in the anteroposterior and vertical dimensions. The period of highest growth was found for the age group <19 years. In conclusion, when compared to serial growth assessment using cephalometric radiographs and clinical photographs,
the sensitivity of SPECT bone scintigraphy to determine condylar growth was 32.4–67.6%, and the specificity to detect growth cessation was 36.1–78.3%. As a diagnostic tool, SPECT bone scintigraphy did not achieve an acceptable sensitivity or specificity, and it is therefore not justifiable to use this tool for the routine assessment of growth in patients with condylar hyperplasia. Funding
No sources of funding were obtained for this research. Competing interests
No competing interests identified. Ethical approval
Ethical approval was obtained from the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster. This study has been registered with the HKU Clinical Registry (Study Identifier Trials HKUCTR-2127). Patient consent
Patient consent was obtained for the use of the clinical photographs in Fig. 3. Acknowledgements. The authors would like to acknowledge the kind support and advice from Ms Samantha Li over the duration of the study.
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Address: Yiu Yan Leung Discipline of Oral and Maxillofacial Surgery Faculty of Dentistry The University of Hong Kong Prince Philip Dental Hospital 34 Hospital Road Sai Ying Pun Hong Kong Tel.: +852 2859 0511 Fax: +852 2857 5570 E-mail: [email protected]
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Int. J. Oral Maxillofac. Surg. 2017; xxx: xxx–xxx http://dx.doi.org/10.1016/j.ijom.2017.09.008, available online at http://www.sciencedirect.com
Clinical Paper Orthognathic Surgery
SPECT bone scintigraphy for the assessment of condylar growth activity in mandibular asymmetry: is it accurate?
B. H. Chan, Y. Y. Leung Oral and Maxillofacial Surgery, Faculty of Dentistry, The University of Hong Kong, Prince Philip Dental Hospital, Sai Ying Pun, Hong Kong
B. H. Chan, Y. Y. Leung: SPECT bone scintigraphy for the assessment of condylar growth activity in mandibular asymmetry: is it accurate?. Int. J. Oral Maxillofac. Surg. 2017; xxx: xxx–xxx. ã 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Abstract. The comparison of serial radiographs and clinical photographs is considered the current accepted standard for the diagnosis of active condylar hyperplasia in patients with facial asymmetry. Single photon emission computed tomography (SPECT) has recently been proposed as an alternative method. SPECT can be interpreted using three reported methods absolute difference in uptake, uptake ratio, and relative uptake. SPECT findings were compared to those from serial comparisons of radiographs and clinical photographs taken at the time of SPECT and a year later; the sensitivities and specificities were determined. Two hundred patient scans were evaluated. Thirty-four patients showed active growth on serial growth assessment. On comparison with serial growth assessment, the sensitivity and specificity of the three methods ranged between 32.4% and 67.6%, and 36.1% and 78.3%, respectively. Analysis using receiver operating characteristic (ROC) curves revealed area under the curve (AUC) values of <0.58. The average age (mean standard deviation) of patients with active growth was 18.6 2.8 years, and average growth in the anteroposterior, vertical, and transverse directions was 0.94 0.91 mm, 0.88 0.86 mm, and 1.4 0.66 mm, respectively. With such low sensitivity and specificity values, it is not justifiable to use SPECT in place of serial growth assessment for the determination of condylar growth status.
Accepted for publication
Facial asymmetry is an aesthetically and functionally unsatisfactory condition that may arise from a number of causes, such as joint resorption, infection-related growth disturbances, and neoplastic changes, among others1–3. Amongst these
ence, developmental causes, and heredity or genetics, have been suggested1. Progressive condylar growth eventually results in alterations to the dimensions of the condylar neck, ramus, and body of the mandible6. A gradual progression
0901-5027/000001+010
causes, condylar hyperplasia is a pathological condition that presents as a progressive and excessive growth of one or both mandibular condyles3–5. It has an unknown aetiology, although possible causes including trauma, functional influ-
Key words: condylar hyperplasia; SPECT bone scintigraphy; serial radiograph tracing; sensitivity; specificity.
ã 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Chan BH, Leung YY. SPECT bone scintigraphy for the assessment of condylar growth activity in mandibular asymmetry: is it accurate?, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.09.008
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Chan and Leung
of the asymmetry over a long period of time of several years has been observed to occur, but it may also occur within a short time span of weeks to months. The condition may present in early childhood at 6–7 years of age, or at any time during the patient’s adolescence growth period, and even after the cessation of skeletal bone growth7,8. This makes the timing of treatment commencement crucial and possibly difficult to predict. The incidence has been reported to be higher in females, with more than 64% of those presenting with the condition being female according to a systematic review by Raijmakers et al.9; however, other studies have not shown this sex difference10. Condylar hyperplasia was first described by Robert Adams in 1836 and then, amongst others, by George Humphry in 1856, who reported dentofacial deformity with resultant chin deviation as the characteristics of this condition. This is also correlated to dental malocclusion with a non-incident dental midline and unilateral crossbite or open bite3. In 1986, Obwegeser and Makek classified condylar hyperplasia into two main types, namely hemimandibular hyperplasia and hemimandibular elongation11. These presentations may occur individually or in combination, to result in the eventual dentofacial asymmetry. Numerous other classifications have been suggested1,12, illustrating the difficulties faced in describing this condition. While the condition is generally selflimiting, the extent of the gross asymmetry is dependent on the extent of condylar hyperplastic growth activity10,13. The condition may contribute to functional and aesthetic deficits, which may result in a negative impact on the patient’s quality of life and function. A study conducted by Naini et al. showed that the patient’s desire to seek surgical treatment for the correction of this condition was correlated with the severity of the asymmetry14. It was also found that a small 5 mm deviation is noticeable to the layperson. The use of serial observation of growth and serial cephalometric and dental model comparisons is considered as the current accepted standard for the determination of condylar growth status4,15,16. This technique requires a minimum period of time between observations (usually 6 months to 1 year) in order to determine the status, which is time-consuming. The findings from the comparisons can only reveal past growth history, and they do not allow the future condylar growth potential to be determined15,17. Bone scintigraphy has been used to aid in the determination of bone growth activ-
ity since the early 1980s. The initial method of scintigraphy involved capture in planar view, with the amount of uptake by the condyles correlated to the T4 spine. This required separate imaging of the T4 spine, as it could not be captured within the condylar view. In recent years, single photon emission computed tomography (SPECT) has been proposed as a more accurate and reliable form of bone scintigraphy, as it allows the three-dimensional evaluation of condylar uptake. The clivus bone, which is situated at the skull base, is considered to be metabolically stable after the fusion of the spheno-occipital synchondrosis. It is used as a reference point for comparison of uptake values in the condyles15,18,19. As the clivus is also captured along with the condyles during the scan, there is no need for two separate images to be captured. However, it has been reported that bone scans are sensitive but not specific, and that conditions affecting the joints, such as healing bone (post-surgery or trauma), joint infection, inflammation (arthritis), and neoplastic changes, can result in a positive scan value20–23. The reported sensitivity and specificity of SPECT scans has varied amongst studies. Sensitivity values of between 78% and 98%, with a pooled sensitivity of 90%, and specificity values of between 60% and 95%, have been reported13,19,24. In the study by Saridin et al., the optimal cutoff value for comparison between the affected and contralateral condyles was determined to be 55%, and the reported sensitivity and specificity were around 88%19. Another study suggested that the optimal cut-off is 56%, with sensitivity of 93% and specificity of 96%, based on the area under the receiver operating characteristics curve4. However, the results from these previous studies supporting SPECT scans were obtained by deriving the outcomes from analyzing patients with condylar hyperplasia at a single clinical time point only, and there was no additional external validation or comparison of the results to an accepted standard. Hence, there is a knowledge gap regarding the true sensitivity and specificity of SPECT as a diagnostic test. As it appears that there have been no previous studies comparing SPECT against a reliable standard, and with the reported wide range of sensitivity and specificity values, it remains necessary to measure the accuracy and reliability of SPECT. Such an evaluation is also required to justify exposing patients to the additional radiation (4 mSv per exposure) of the SPECT scan. The aims of this study were to determine the sensitivity and specificity of
SPECT bone scintigraphy when used in patients with facial asymmetry arising from condylar hyperplasia, and to identify general patterns of condylar growth in the study population according to sex and age groups. Materials and methods
Patients with mandibular asymmetry caused by condylar hyperplasia, who presented to the Discipline of Oral and Maxillofacial Surgery, Faculty of Dentistry, The University of Hong Kong between January 2011 and July 2013, and who underwent SPECT bone scintigraphy for pre-treatment assessment, were recruited. Patients who fulfilled the following criteria were included: (1) mandibular asymmetry as a result of condylar hyperplasia; (2) availability of lateral and postero-anterior cephalometric radiographs taken around the time of SPECT bone scintigraphy and 1 year afterwards. Patients with the following conditions were excluded: (1) history of temporomandibular joint surgery; (2) presence of a neoplastic pathology of the temporomandibular joint, e.g. osteochondroma; (3) presence of systemic diseases that could potentially affect the temporomandibular joint, e.g. autoimmune conditions; (4) congenital conditions and syndromes that are associated with facial asymmetry, e.g. hemifacial microsomia. SPECT bone scintigraphy and analysis
SPECT scans were performed 2–4 h after the intravenous administration of 20–25 mCi technetium 99m-methylene diphosphonate (99mTc-MDP). A region of interest (ROI) of 16 pixels 3 slices was drawn over both condylar heads. The individual condylar counts within the ROIs were calculated and expressed as an average against the clivus bone count. The determination of active condylar growth from the condylar counts was assessed using three reported methods. The first was the absolute difference in uptake (i.e. active inactive)25, in which the condylar count of the inactive condyle was subtracted from that of the active condyle. A difference in scan values of 0.34 0.40 (mean standard deviation (SD)) between the active and inactive condyles was considered to indicate active growth. The second method was the uptake ratio, i.e. (active/inactive) 100%5,16,26, in which the ratio of the active condylar count against the inactive condylar count was calculated as a percentage. Growth was considered to be
Please cite this article in press as: Chan BH, Leung YY. SPECT bone scintigraphy for the assessment of condylar growth activity in mandibular asymmetry: is it accurate?, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.09.008
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Diagnostic accuracy of SPECT active if the percentage was more than 10%, and vice versa. The third method was the relative uptake (condylar activity percentage), i.e. (active/(active + inactive)) 100%5,10,16,19,27, in which the active condylar count over the total condylar count was calculated as a percentage. Growth was considered to be active if the uptake value percentage was 55% or more. Serial radiographic tracings and growth assessment
Lateral and postero-anterior (PA) cephalometric radiographs (magnification 1.23, Orthoralix 9200 X-ray system; Gendex, Hatfield, Pennsylvania, USA) were traced using an overlay ortho/ trace film 0.003 matte acetate for the baseline radiographs taken at the time of the SPECT scan. The lateral and PA
cephalometric radiographs that were taken 1 year after were then traced and compared to the baseline radiographs of the same patient. Stable anatomical landmarks on the radiographs were traced. For the lateral cephalometric radiographs, the base of the skull, orbital rims, and the condylar head were marked as the reference landmarks. To determine the presence of growth, the posterior and inferior borders of the mandible and the chin region were traced. Any visible growth in the vertical and anteroposterior direction was detected and measured from the menton and pogonion, respectively, with a clear plastic ruler with 0.5-mm-interval markings (Fig. 1). For the PA cephalometric radiographs, a horizontal reference plane (x-axis) was drawn between the right and left lateral orbitale (LO) landmarks. A vertical line (y-axis) was dropped perpendicular to the
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horizontal plane using the crista galli as the reference point, towards the inferior border of the anterior mandible. The distance on the x-axis from menton to the vertical line was measured and compared to detect any changes in the transverse direction (Fig. 2). Additional comparisons were performed for patients with clinical photographs available that were taken at the time of the SPECT scan and a year later. Intraoral photographs of the same patient taken at a 1-year interval were also compared. The frontal, profile, and intraoral photographs were overlapped using Dolphin Imaging software (version 11.9.07.24 Premium; Dolphin Imaging and Management Solutions, Chatsworth, CA, USA) for correlation with the findings from the serial radiographic tracings (Fig. 3). Growth was considered to be active if any of the three assessments (lateral ceph-
Fig. 1. Tracing of a lateral cephalometric radiograph.
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Chan and Leung against the findings of the serial growth assessment. Receiver operating characteristics (ROC) curves were also plotted to compare the different methods, and the method that had a curve closest to the upper left quadrant had the best diagnostic ability. The area under the curve (AUC) was also calculated for each method.
Results
Fig. 2. Comparison of transverse growth on postero-anterior cephalometric radiographs. LO, lateral orbitale; CG, crista galli; Me, menton.
alometric serial tracing, PA cephalometric serial tracing, and clinical photographic changes) showed any changes. If none of these assessments showed any changes across the 1-year interval, the subject was considered to be inactive for growth. Comparison of SPECT bone scintigraphy and serial growth assessment
The results from SPECT bone scintigraphy were compared to the growth status results determined in the serial growth assessment. For each patient, the results for the three SPECT analysis methods were compared against the findings of the serial growth assessment. The numbers of true-positives (where a positive SPECT finding corresponded with a positive serial growth status) and true-negatives (where a negative SPECT finding corresponded with a negative serial growth status) were calculated. The sensitivity was calculated as the percentage of true-positives over the total positive results for each SPECT analysis method, and the specificity was cal-
culated as the percentage of true-negatives over the total negative results. Statistical analysis
The statistical analysis was performed using IBM SPSS Statistics version 23.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics, including the mean SD, were used to describe the demographic background of the samples. The mean movements of menton and pogonion for patients with active growth were also obtained. Significant differences in growth between sex and age groups were determined using the parametric t-test for data following a normal distribution, and the nonparametric Mann–Whitney U-test for data that did not. Significant differences in proportions of patients with active growth according to sex and age groups were calculated with the Pearson x2 test. A 5% level of significance was applied. The sensitivity and specificity of the three assessment methods were calculated
A total of 265 patients were initially recruited into the study, of whom 65 were excluded based on the exclusion criteria. Of the 200 patients included, 82 (41%) were male and 118 (59%) were female, giving a male to female ratio of approximately 1:1.43. The mean age of the patients was 21.0 4.3 years; the mean age of male patients was 21.7 4.0 years and of female patients was 20.6 4.4 years. The general demographic data of the 200 patients are presented in Table 1. Serial tracings of the scans of 200 patients were analyzed, and 34 patients (17%) were found to have active growth in at least one of the three measured dimensions; of these patients, 21 (61.8%) were female and 13 (38.2%) were male. The SPECT scans were analyzed and the findings are presented in Table 2. With regard to the absolute difference in uptake measurement, 47 patients were found to have active growth. When the uptake ratio was calculated, 129 patients were found to have active growth, and when relative uptake was measured, 68 patients had active growth. There were statistically significant differences (P < 0.001) between the proportions of active scan results between the three methods of SPECT scan measurement, indicating poor validity amongst them. The findings of the SPECT scans were compared to those from serial growth assessment, as illustrated in Table 3. Each SPECT analysis method was compared against the serial growth assessment, and the numbers of true active and inactive findings were determined. The absolute difference in uptake measurement identified 11 true active patients, which was the lowest result among the three methods. The uptake ratio identified 23 true active patients and the relative uptake identified 14 true active patients. When the true inactive findings were compared, the uptake ratio identified the lowest number of true inactive findings with 60 patients; the absolute difference in uptake identified 130 true inactive patients and relative uptake identified 112 true inactive patients.
Please cite this article in press as: Chan BH, Leung YY. SPECT bone scintigraphy for the assessment of condylar growth activity in mandibular asymmetry: is it accurate?, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.09.008
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Diagnostic accuracy of SPECT
Fig. 3. Comparison of clinical photographs. (a) Frontal photographs showing vertical and transverse growth. (b) Lateral photographs showing vertical growth at menton. (c) Frontal intraoral photographs of the dentition, using the upper anterior teeth as reference; growth is noted from the difference in lower anterior teeth positions.
The sensitivity and specificity of the three methods are presented in Table 4. The absolute difference in uptake yielded the lowest sensitivity at 32.4% and the uptake ratio had the highest sensitivity at 67.6%; the sensitivity of relative uptake was 41.2%. With regard to specificity, the uptake ratio had the lowest specificity at 36.1%, relative uptake had a specificity of
67.5%, and the absolute difference in uptake had the highest specificity at 78.3%. The sensitivity and specificity of all three methods are considered to be low. The ROC curves for the three methods are presented in Fig. 4. All three methods had low AUC values of less than 0.58, indicating that the ability of the three SPECT analysis methods to detect growth
Table 1. Patient demographic characteristics. Number (%) Male Female Total
82 (41) 118 (59) 200
SD, standard deviation.
Age (years), mean SD 21.7 4.0 20.6 4.4 21.0 4.3
Active growth, number (%) 13 (38.2) 21 (61.8) 34
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was only slightly more than random chance. An AUC of 0.50 is equivalent to random chance. Based on the findings of the primary outcome of sensitivity and specificity, and supported by the AUC calculations, the three SPECT analysis methods proposed are not suitable to be used as a diagnostic tool for condylar hyperplasia. Further analyses of the findings from the serial growth assessment were performed; the results are presented in Table 5. Thirty-four of the total 200 patients (17%) had active growth. The average age of the patients with true active growth as determined from the serial growth assessment was 18.6 2.8 years. The average age of the male patients with active growth was 19.2 2.9 years, and the average age of the female patients with active growth was 18.3 2.7 years. There was no statistically significant difference in the proportion of patients with active growth between the male and female patients (P = 0.719). Further stratification of the sample population by age groups was done (Table 6). Of the 34 patients with active growth, 10 were younger than 17 years old. Eleven patients were aged 17 to <19 years, seven were between 19 and <21 years old, and six were 21 years old. Patients below the age of 19 years accounted for more than half (61.7%) of the patients with active growth. The age group of <17 years had the highest percentage of patients with active growth (47.6%) when compared to the other age groups; correspondingly, the age group 21 years had the lowest percentage of patients with active growth (7.6%). A general trend was observed, in which approximately half of the patients below 17 years of age had active growth. This percentage then further halved in each subsequent age group, with 7.6% of patients with active growth in the 21 years age group (Fig. 5). There were significant differences in the proportions of patients with active growth in those <17 years of age compared to the other three age groups. A significant difference was also found between the 17 to <19 years group and the 21 years group (P = 0.021). There was no other difference in the proportions of patients with active growth for the other comparisons. The amounts of growth in the anteroposterior, vertical, and transverse directions in the 34 patients with active growth were recorded; the results are presented according to sex in Table 7. The average growth was 0.94 0.91 mm in the anteroposterior direction, 0.88 0.86 mm in the vertical direction, and 1.4 0.66 mm
Please cite this article in press as: Chan BH, Leung YY. SPECT bone scintigraphy for the assessment of condylar growth activity in mandibular asymmetry: is it accurate?, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.09.008
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Table 2. Analysis of SPECT scans. Method
Number (%)
Growth status from serial growth assessment Active Inactive
34 (17) 166 (83)
Absolute difference in uptake Active Inactive
47 (23.5) 153 (76.5)
Uptake ratio Active Inactive
129 (64.5) 71 (35.5)
Relative uptake Active Inactive
68 (34) 132 (66)
Differences in proportion of active counts P < 0.001a,* P < 0.001a,* P < 0.001a,*
Absolute difference versus uptake ratio Absolute difference versus relative uptake Uptake ratio versus relative uptake * a
Significant difference (P < 0.05). Pearson x2 test.
Table 3. Comparison of SPECT scans and serial growth assessment. Serial growth assessment SPECT assessment
Active
Inactive
Total
Absolute difference in uptake
Active Inactive Total
11 23 34
36 130 166
47 153 200
Uptake ratio
Active Inactive Total
23 11 34
106 60 166
129 71 200
Relative uptake
Active Inactive Total
14 20 34
54 112 166
68 132 200
in the transverse direction. For the male patients, the average anteroposterior, vertical, and transverse growth was 1.3 1.1 mm, 1.2 1.1 mm, and 1.3 0.43 mm, respectively. For the female patients, the average anteroposterior change was 0.69 0.68 mm, vertical change was 0.69 0.62 mm, and transverse change was 1.5 0.78 mm. There was a significant difference in
the amount of anteroposterior growth between male and female patients (P = 0.039), with male patients exhibiting significantly more anteroposterior growth than female patients. Analysis of the vertical and transverse growth between the sexes did not reveal any significant difference (P = 0.232 and P = 0.753, respectively).
A further analysis of the amount of growth exhibited by true active growth patients was performed by stratifying the patients into the age ranges. The findings are presented in Table 8. Patients <19 years of age appeared to have higher yearly growth amounts as compared to patients aged 19 years. However, there was no significant difference between the mean anteroposterior (P = 0.169), vertical (P = 0.552), and transverse (P = 0.193) growth between the two age groups. Discussion
The key findings of this study were (1) the sensitivity of the three analysis methods of SPECT bone scintigraphy to determine condylar growth ranged between 32.4% and 67.6%, and the specificity between 36.1% and 78.3%; and (2) the AUC of the ROC curves was low at <0.58. Both key findings show that SPECT scans were poor for determining condylar growth status. The proportions of patients with active condylar growth in the age groups <17 years, 17 to <19 years, 19 to <21 years, and 21 years were 47.6%, 21.6%, 14.3%, and 7.6%, respectively. The treatment of patients with condylar hyperplasia is determined by the progression of the individual’s condylar growth. There are advantages and disadvantages to both commencing treatment earlier and adopting a watch-and-wait approach in the management of such patients. The condition tends to present during the patient’s adolescence period and may continue even after the cessation of skeletal bone growth. This gradual dentofacial asymmetry and its attendant dental malocclusion will no doubt result in some negative impact on the patient’s selfimage and confidence. The patients in this study presented with the condition at a young age – at an average of 21.0 4.3 years. This is in line with the findings reported by other
Table 5. Serial growth assessment. Table 4. Sensitivity and specificity of SPECT methods. Number (%) Absolute difference in uptake True-positive (sensitivity) True-negative (specificity)
11 (32.4) 130 (78.3)
Uptake ratio True-positive (sensitivity) True-negative (specificity)
23 (67.6) 60 (36.1)
Relative uptake True-positive (sensitivity) True-negative (specificity)
14 (41.2) 112 (67.5)
Factor
Number (%)
Growth status Active Inactive
34 (17) 166 (83)
Patients with active growth Male Female Difference in proportion of active growth between the sexes Mean age of patients with active growth, mean SD Total: 18.6 2.8 years Male: 19.2 2.9 years Female: 18.3 2.7 years
13 (38.2) 21 (61.8) P = 0.719a
SD, standard deviation. a Pearson x2 test.
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Diagnostic accuracy of SPECT Table 6. Age group characteristics—serial growth assessment. Patients with active growth by age
Number (%)
<17 years Male Female
10 (29.4) 3 7
17 to <19 years Male Female
11 (32.4) 4 7
19 to <21 years Male Female
7 (20.6) 4 3
21 years Male Female
6 (17.6) 2 4
Proportion of patients with active growth in the age group
n/N (%)
<17 years 17 to <19 years 19 to <21 years 21 years
10/21 (47.6) 11/51 (21.6) 7/49 (14.3) 6/79 (7.6)
Differences in proportion of active counts <17 years <17 years <17 years 17 to <19 17 to <19 19 to <21 * a
vs. 17 to <19 years vs. 19 to <21 years vs. 21 years years vs. 19 to <21 years years vs. 21 years years vs. 21 years
P = 0.027a,* P = 0.003a,* P < 0.001a,* P = 0.343a P = 0.021a,* P = 0.223a
Significant difference (P < 0.05). Pearson x2 test.
authors7,8. The average age of females was generally younger than male patients by 1 year. This indicates that the condition is already present at an earlier age, as the majority of the patients were already found to have ceased growing when assessed (166 out of 200). The average age of the 34 patients with active growth
was younger, at 18.6 2.8 years. This is approximately 3 years lower than the overall average. Females with active growth also generally presented 1 year earlier than the male patients. This study also supports the higher incidence of the condition in females, as 59% of the scans were done for female
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patients. There were also more females within the active growth group, with 21 of the 34 patients (61.8%) being female. As determined in this study, the three SPECT methods had sensitivity between 32.4% and 67.6%, and specificity between 36.1% and 78.3%. Further analysis using ROC curves revealed AUC values of <0.58, indicating that the methods are no better than random chance. This was corroborated by statistically significant differences between the findings of the three methods, indicating poor validity and accuracy. Such low sensitivity and specificity values would result in a large percentage of false-positive and false-negative diagnoses, which would hinder and potentially negatively affect the treatment outcomes of patients. Two main treatment methods are currently proposed and practiced, namely high condylectomies and orthognathic surgery, or a combination of both6,28,29. These two methods are highly dependent on the clinician’s ability to accurately determine the patient’s growth status, as high condylectomies are used to arrest further growth of the affected condyle and orthognathic surgery should only be done after the cessation of growth. However, with such low sensitivity and specificity values, the use of SPECT scans would result in a number of false-positive and false-negative cases, which would lead to unnecessary over-treatment (high condylectomy or unnecessary growth reviews) for patients who are false-positive, or premature commencement of treatment (orthognathic surgery) for patients who are false-negative. Another
Fig. 4. Receiver operating characteristic (ROC) curves for SPECT. AUC, area under the curve; CI, confidence interval.
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Chan and Leung
Fig. 5. Percentage of patients with active growth in each age group, as assessed using serial radiographs.
Table 7. Growth in the anteroposterior, vertical, and transverse direction according to sex; mean SD values. Growth in males Growth in females Average growth
Anteroposterior
Vertical
Transverse
1.3 1.1 mm 0.69 0.68 mm 0.94 0.91 mm
1.2 1.1 mm 0.69 0.62 mm 0.88 0.86 mm
1.3 0.43 mm 1.5 0.78 mm 1.4 0.66 mm
Differences according to sex Anteroposterior growth between males and females Vertical growth between males and females Transverse growth between males and females
P = 0.039a,* P = 0.232b P = 0.753b
SD, standard deviation. * Significant difference (P < 0.05). a Parametric t-test. b Non-parametric Mann–Whitney U-test performed for data that did not follow a normal distribution.
Table 8. Growth in the anteroposterior, vertical, and transverse direction according to age; mean SD values. <17 years 17 to <19 years 19 to <21 years 21 years
Anteroposterior
Vertical
Transverse
1.0 1.0 mm 1.2 1.0 mm 0.42 0.53 mm 0.83 0.6 mm
0.9 0.77 mm 0.86 0.67 mm 1.4 1.3 mm 0.33 0.4 mm
1.7 0.70 mm 1.0 0.38 mm 1.5 0.91 mm 1.7 0.4 mm
Difference according to age group Anteroposterior growth between <19 years and 19 years Vertical growth between <19 years and 19 years Transverse growth between <19 years and 19 years
P = 0.169a P = 0.552a P = 0.193a
SD, standard deviation. a Non-parametric Mann–Whitney U-test performed for data that did not follow a normal distribution.
major drawback of using SPECT is the need to expose patients to the highly radioactive 99mTc-MDP intravenous contrast during scans. The effective dose of a single SPECT scan is 4 mSv (4000 mSv), which is the equivalent of 200 chest X-rays (0.02 mSv)30, or 1.8 years of background radiation. In contrast, a panoramic radiograph has an effective dose of only 36 mSv, and a cone beam computed tomography (CBCT) scan only 432 mSv31,32. Wu et al. performed a study to predict the cancer risks from dental computed tomography and reported that the risk of cancer induction was higher if the exposed patient was younger, and also that females were at a higher risk than males32. This could be extrapolated to the use of 99mTcMDP for the purpose of determining condylar growth activity. SPECT scans for the purpose of condylar growth determination are typically done on younger patients, and with the higher prevalence of condylar hyperplasia in females, the majority of patients being exposed to radiation would be young females. A more worrying trend that was noted during this study was the taking of the raw condylar scan results at face value, which led to the diagnosis of a condyle with a higher count as active. Such diagnoses of active condylar growth were found to be prevalent during the reporting of the SPECT scans results. A small number of
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Diagnostic accuracy of SPECT patients were also noted to have been subjected to repeated SPECT scans during their follow-up period, and it is the authors’ view that they were unnecessary. The main limitation of this study was the retrospective nature of the research. This limitation was overcome by the use of a well-developed treatment protocol and a detailed records system for patients who required skeletal growth monitoring in the unit. The findings of this study, however, suggest that it would be unethical to design a prospective study with similar aims and objectives, as the SPECT scans were proved to have low sensitivity and specificity. Also, with the high dosage of radiation exposure for relatively young individuals, it might be more valuable to design prospective studies to investigate three-dimensional mandibular growth patterns using advanced imaging techniques with a lower radiation exposure, such as CBCT. Other limitations of this study were that it was conducted at a single centre with a sample population comprising mainly patients of Asian descent. The study also only included patients with facial asymmetry caused by condylar hyperplasia. Therefore, the extrapolation of the findings from this study may not be wholly accurate when applied to a different geographical or racial group. Several considerations regarding the determination of condylar growth activity can be summarized from the findings of this study: (1) females were found to present with condylar hyperplasia at an earlier age, and correspondingly ceased their growth activity at an earlier age. (2) Male patients in general were found to present with condylar hyperplasia later than female patients and ceased their growth activity later. It would therefore be prudent not to commence definitive orthognathic surgery too early in male patients if condylar hyperplasia is noted. (3) Approximately half of the patients under the age of 17 years were found to have active condylar growth. This proportion halved in each subsequent age group, until only approximately 7% of patients 21 years of age were found to have active condylar growth. (4) The average change at the chin point over 1 year in the anteroposterior, vertical, and transverse dimensions was 0.94 mm, 0.88 mm, and 1.4 mm, respectively, with male patients growing almost twice as much as female patients in the anteroposterior and vertical dimensions. The period of highest growth was found for the age group <19 years. In conclusion, when compared to serial growth assessment using cephalometric radiographs and clinical photographs,
the sensitivity of SPECT bone scintigraphy to determine condylar growth was 32.4–67.6%, and the specificity to detect growth cessation was 36.1–78.3%. As a diagnostic tool, SPECT bone scintigraphy did not achieve an acceptable sensitivity or specificity, and it is therefore not justifiable to use this tool for the routine assessment of growth in patients with condylar hyperplasia. Funding
No sources of funding were obtained for this research. Competing interests
No competing interests identified. Ethical approval
Ethical approval was obtained from the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster. This study has been registered with the HKU Clinical Registry (Study Identifier Trials HKUCTR-2127). Patient consent
Patient consent was obtained for the use of the clinical photographs in Fig. 3. Acknowledgements. The authors would like to acknowledge the kind support and advice from Ms Samantha Li over the duration of the study.
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Address: Yiu Yan Leung Discipline of Oral and Maxillofacial Surgery Faculty of Dentistry The University of Hong Kong Prince Philip Dental Hospital 34 Hospital Road Sai Ying Pun Hong Kong Tel.: +852 2859 0511 Fax: +852 2857 5570 E-mail: [email protected]
Please cite this article in press as: Chan BH, Leung YY. SPECT bone scintigraphy for the assessment of condylar growth activity in mandibular asymmetry: is it accurate?, Int J Oral Maxillofac Surg (2017), http://dx.doi.org/10.1016/j.ijom.2017.09.008