Reliability of Cone Beam CT for Morphometry of Nasolabial Soft Tissue in Patients with Skeletal Class III Malocclusion: A Qualitative and Quantitative Analysis

Background(cid:0)Precise measurement of the morphological structure of soft and hard tissues is fundamental to the treatment of malocclusion, but the ability of cone beam CT(CBCT) for soft tissue measurements involves few studies to date. The purpose of this study was to assess the reliability of CBCT for nasolabial soft tissue measurements in patients with skeletal class III malocclusion based on 3-dimensional(3D) facial scanner results. Methods(cid:0)CBCT and 3D facial scan images of 20 orthognathic patients were used in this study. 11 soft tissue landmarks and 15 linear and angular measurements were identied and performed. For qualitative evaluation, Shapiro-Wilk Test and Bland-Altman plots were applied to analyze the equivalence of the measurements derived from these two kinds of data. To quantify specic deviation of CBCT measurements from facial scanner, the latter were set as a benchmark, and mean absolute difference(MAD) and relative error magnitude(REM) for each variable were calculated. Results(cid:0)Statistically signicant differences were observed on length measurements of bilateral philtrum crests, width of mouth and angular measurements of the protrusion angle of lower lip, left angle of upper mouth and nasolabial angle between the two methods. The MAD value for all length measurements were less than 2 mm and for angular variables <8°. The average MAD and REM for length measurements was 0.94mm and 5.64% respectively, and 2.27°, 3.78% for angular measurements. Conclusions(cid:0)Certain inconformity exists in regions of nasal base and lower lip vermilion between CBCT and facial scanner when measuring nasolabial surfaces, but most of them are clinically acceptable. The soft tissue results measured by CBCT showed relatively good reliability and can be used for 3D measurement of soft tissue in the nasolabial region clinically.

The prediction of soft tissue changes is dependently based on the precise measurement of their morphological characteristics, which has been made possible by the development of 3D imaging techniques. Facial scanner is a well-established device currently used in the clinic, which can record the texture and characteristics of facial skin three-dimensionally, leading clinicians to be increasingly accurate in studying changes in facial soft tissue before and after treatment. Commonly used are 3DMD, Morpheus 3D, etc., and their precision and accuracy have been veri ed by previous studies [16][17][18][19]. Nevertheless, facial scanner can only record the morphology of soft tissues, which needs to be fused with CBCT when to explore the relationships and ratios of soft and hard tissues [20,21], thus possibly bringing the technical error when the two data fuse, which in turn affects the measurement results, and soft tissues imaged by CBCT avoid this problem [22].
Three-dimensional cephalometric technique based on CBCT is one of the hot topics in orthodontic and orthognathic clinical research in recent years [23][24][25]. Traditionally, cephalometric measurements involve both soft and hard tissues. There is no doubt about the ability of CBCT for hard tissue measurements, whereas its ability to measure soft tissue morphology involves fewer studies to date. Precise measurement of the morphological structure of soft and hard tissues is fundamental to the development of 3D cephalometric techniques, and thus deserve intensive study.
The purpose of this study, therefore, was to qualitatively analyze whether CBCT reconstructed facial soft tissue models show statistically signi cant differences compared with 3D facial scanner when used for soft tissue morphometry. Meanwhile, using 3D facial scanner measurements as a benchmark, to quantitatively analyze the degree of speci c deviation of the CBCT measurement variables, so as to provide reference and guidance for the clinical application of CBCT in soft tissue measurement and 3D cephalometric analysis, and nally promote the clinical use of CBCT. Methods:

Samples selection
This study was carried out at the Department of Stomatological Hospital of Chongqing Medical University, China after the ethical approval and study protocol was approved (CQHS-REC-2021001).
Written informed consent for the participation in the study and the publication of their identifying images in an online open-access publication platform has been obtained from all subjects. We con rm that all methods were performed in accordance with the relevant guidelines and regulations.
The CBCT and 3D facial scan images of 20 orthognathic patients (ten women) were used. Two types of image were taken at the same time for diagnostic purposes. All patients underwent the same surgery procedure-maxillary Le Fort I osteotomy and mandibular bilateral sagittal splint ramus osteotomy to treat skeletal class III malocclusion, which were performed by a same surgeon from the above hospital.
Patients with congenital syndromes, systematic diseases, cleft lip /palate, temporomandibular joint disorder or facial trauma were excluded. Data acquisition CBCT (KaVo Dental Gmb H, USA; 80 mA, 8.9-second scan time) scans were acquired at a 0.4 mm* 0.4 mm* 0.4 mm voxel size level and set at a matrix of 400 × 400 pixels in each CT slice and a 0.25 mm slice thickness. The CBCT data were then stored into a specialized computer in Digital Imaging and Communications in Medicine (DICOM) format, and were converted in to 3D models for measurement with a 3D reconstruction software, Mimics 19.0, (Materialise, Leuven, Belgium). To obtain the optimal facial soft tissue models, the threshold values for Houns eld units(HU)were set as -718 to -177 HU and smooth procedure was performed. After these processes, the 3D facial soft tissue images reconstructed by CBCT were obtained.
The facial scanner Morpheus 3D (Morpheus, Gyoung-gi, Korea) was used for 3D facial surface scan, which emitted white structured light to the patient and ne texture of facial skin can be obtained. Other parameters of this device included a scan time of 0.8 seconds, a scan accuracy of 0.1mm and an image resolution of 1024x768 ppi. After scanning process, the images were then auto-synthesized by the MDS software of the device (Morpheus, Gyoung-gi, Korea), and the 3D facial scan models were obtained.
Variables measurement 11 soft tissue landmarks and 15 linear and angular measurement variables were used in this study ( Figure 1, Figure 2 and Table 1). Landmarks location and variables measurement were performed in CBCT model and 3D facial scan models respectively using a mouse-driven graphics cursor in 3D view. To assess the intra-observer reproducibility, the rst author located the landmarks twice at an interval of 2 weeks, and the intra-class correlation (ICC) analysis was performed at 95% con dence intervals. All variables were measured twice in two-week interval by the same operator, and the mean of the two measured values was used for nal statistical analysis. Table 1 De nition of landmarks and measurements in this study

Item
De nition

Statistical analysis
The data of this study were analyzed using SPSS 26.0 software (IBM Co., Armonk, NY, USA) and MedCalc Software (version 20.009, Ostend, Belgium) For qualitative evaluation, the Shapiro-Wilk Test was applied to analyze the distribution characteristics of the data and the Bland-Altman plots was used to analyze the equivalence between measurements derived from these two kinds of model. To determine the equivalence of the 2 methods, the line of equality (difference=0) must contain entirely within the 95% con dence interval of their mean difference. To quantify speci c deviation of CBCT measurements from facial scanner, the results of the latter were set as a benchmark, and mean absolute difference(MAD) and relative error magnitude(REM) for each variable were calculated. The calculation was performed as follows: Results: The high ICC value (ranging from 0.894 to 0.913) indicated good intra-observer reliability in this study, and the Shapiro-Wilk Test results showed that the data t a normal distribution. Table 2 shows linear and angular measurement results of the facial scanner and CBCT respectively. In Table 3 and   The quantitative analysis results of linear and angular measurement differences between facial scanner and CBCT are shown in Table 4 and Table 5. For linear measurements, the average MAD was 0.94mm and the average REM was 5.64%, and the larger differences manifested in the length of bilateral philtrum crests and the width of the mouth (MAD>1mm). For angular measurements, the average MAD was 2.27°a nd the average REM was 3.78% and the larger differences exhibited in the protrusion angle of the lower lip and the nasolabial angle(MAD>7°).

Discussion:
In this study, 20 CBCT and 3D facial scan data of skeletal class III patients were combined to explore the reliability of CBCT for soft tissue measurements, and the nasolabial region was selected as the research structure. One consideration was based on the special structure of this region-vermilion mucosa and the skin [26]. Since the two structure cannot be distinguished on CBCT images, we sought to explore how accurate the measurements of CBCT are for that, and whether it has an impact on clinical use. The second was its diverse morphological measurements, including the length, angle and symmetry in 3D space, which can cover feature measurements of many areas of the face [27,28].
The results of qualitative evaluation showed that the difference between CBCT and facial scanner in measuring nasolabial structures mainly manifested in the length of philtrum crest on both sides, width of mouth, the protrusion angle of the lower lip, angle of upper mouth on the left side and the nasolabial angle. Maal et al [29] reported that 90% of soft tissues reconstructed by CBCT showed no difference when matched with 3D facial photographs, and the remaining 10% were affected by head position and facial expression at the process of image acquisition. In the present study, statistically signi cant differences were mainly centered on structures located at the nasal base and lower lip, involving bilateral philtrum length and nasolabial angle in the upper lip and the protrusion angle of lower lip. Due to the complex concave characteristics of the nasal base, the accuracy of the landmarks located in this region is compromised [17]. In contrast, landmarks at the junction of the vermilion and skin of the upper lip are easier to identify because of their well-de ned characteristic structures like the Cupid's bow. The accuracy of measurements of the lower lip is mainly affected by the Li-point, which was de ned as the midpoint of the vermilion border of the lower lip by wong et al [30]. Given the reality that the boundary between the vermilion and the skin is not clear on CBCT and the absence of explicit contour structure like the upper lip, thus making its positioning with suboptimal accuracy.
On quantitative analysis, the mean absolute difference in length measurements of CBCT for all variables were less than 2 mm. In the literature, scholars [31,32] reported that clinically acceptable deviations of soft tissue measurements were ranging from 1-3 mm according to the number of landmarks utilized. In this experiment, variables with relatively obvious deviation were the length of bilateral philtrum crests and the oral width, but none of them exceeded 2 mm, thus can be considered as no impact on clinical use. For angular measurements, the deviation of protrusion angle of lower lip and nasolabial angle were both > 7°, but were still classi ed as good measurements [33,34]. For one thing, the angle measurements involve more landmarks, so the corresponding error becomes larger inevitably. For another, according to ndings by Andrade et al [32], the deviation of 3D tools in measuring concave surface structure is relatively large, such as nasolabial angle and mentolabial angle. Patients with skeletal Class III have a smaller nasolabial angle due to insu cient maxillary development, which makes the measurement of this area more di cult. Therefore, in clinical use, one should pay much attention to control the technical error of this region, such as locating the landmarks with a multidimensional view and taking the mean value of multiple measurements.

Declarations
Ethics approval and consent to participate Ethical approval for this study was obtained from the Ethics Committee of Stomatological Hospital of Chongqing Medical University. Written informed consent has been obtained from the participants prior to data collection process.

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We con rm that all methods were performed in accordance with the relevant guidelines and regulations.

Consent for publication
Written informed consent for the publication of their identifying images in an online open-access publication platform has been obtained from all subjects.

Availability of data and materials
The datasets used in the current study are available from the corresponding author on reasonable request.