Axin2 overexpression promotes the early epithelial disintegration and fusion of facial prominences during avian lip development.

The epithelial disintegration and the mesenchymal bridging are critical steps in the fusion of facial prominences during the upper lip development. These processes of epithelial-mesenchymal transition and programmed cell death are mainly influenced by Wnt signals. Axis inhibition protein2 (Axin2), a major component of the Wnt pathway, has been reported to be involved in lip development and cleft pathogenesis. We wanted to study the involvement of Axin2 in the lip development, especially during the epithelial disintegration of facial prominences. Our results show that Axin2 was expressed mainly in the epithelium of facial prominences and decreased when the prominences were about to contact each other between Hamburger-Hamilton stages 27 and 28 of chicken embryos. The epithelial integrity was destructed or kept intact by the local gain or loss of Axin2 expression, resulting in morphological changes in the facial processes and their skeletal derivatives including the maxilla, nasal, premaxilla bone, and their junctions without cleft formation. These changes were related to expression changes in nuclear ß-catenin, pGSK3ß, Slug, Smad3, E-cadherin, and p63. All these data indicate that Axin2 participates in the regulation of epithelial integrity and fusion by promoting epithelial disassociation, basement membrane breakdown, and seam loss during the fusion of facial prominences in lip development.

Long-Term Stability of Pre-Orthodontic Orthognathic Bimaxillary Surgery Using Intraoral Vertical Ramus Osteotomy Versus Conventional Surgery.

PURPOSE: The aim of the present study was to compare the long-term stability of bimaxillary surgery using an intraoral vertical ramus osteotomy (IVRO) with and without presurgical orthodontic treatment. MATERIALS AND METHODS: The present retrospective study included 31 consecutive patients with skeletal Class III malocclusions who had undergone bimaxillary surgery (Le Fort I osteotomy and bilateral IVRO). Patients were divided into 2 groups based on treatment type: pre-orthodontic orthognathic surgery (POGS; n = 17) and conventional surgery with presurgical orthodontic treatment (CS; n = 14). Lateral cephalograms were obtained before surgery, 1 day after surgery, 1 month after surgery, 1 year after surgery, and 2 years after surgery to evaluate skeletal and soft tissue changes between the 2 groups. Data were analyzed using χ2 tests, Mann-Whitney U tests, repeated-measures analyses of variance, and independent t tests. RESULTS: There was no significant difference in skeletal or soft tissue measurements-with the exception of the angle between the sella-and-nasion plane and the occlusal plane (SN-OP; P < .001)-between the CS and POGS groups at 2 years after IVRO. The SN-OP had increased in the CS group but decreased in the POGS group at 2 years after surgery. CONCLUSIONS: These findings suggest that POGS and CS have similar long-term stability in patients with skeletal Class III malocclusion.

Separate development of the maxilla and mandible is controlled by regional signaling of the maxillomandibular junction during avian development.

BACKGROUND: Syngnathia is a congenital craniofacial disorder characterized by bony or soft tissue fusion of upper and lower jaws. Previous studies suggested some causative signals, such as Foxc1 or Bmp4, cause the disruption of maxillomandibular identity, but their location and the interactive signals involved remain unexplored. We wanted to examine the embryonic origin of syngnathia based on the assumption that it may be located at the separation between the maxillary and mandibular processes. This region, known as the maxillomandibular junction (MMJ), is involved in segregation of cranial neural crest-derived mesenchyme into the presumptive upper and lower jaws. RESULTS: Here we investigated the role of Fgf, Bmp, and retinoid signaling during development of MMJ in chicken embryos. By changing the levels of these signals with bead implants, we induced syngnathia with microstomia on the treated side, which showed increased Barx1 and neural cell adhesion molecule (NCAM) expression. Redistribution of proliferating cells was also observed at the proximal region to maxillary and mandibular arch around MMJ. CONCLUSIONS: We propose that interactive molecular signaling by Fgfs, Bmps, and retinoids around MMJ is required for normal separation of the maxilla and mandible, as well as the proper positioning of beak commissure during early facial morphogenesis. Developmental Dynamics 246:28-40, 2017. © 2016 Wiley Periodicals, Inc.

Consecutive condylectomy and molar intrusion using temporary anchorage devices as an alternative for correcting facial asymmetry with condylar hyperplasia.

This case report demonstrates the successful treatment of facial asymmetry with condylar hyperplasia with limited surgical and orthodontic treatment. A high condylectomy was performed to shorten the elongated condyle and to remove its active growth site. The maxillary molars on the affected side were then orthodontically intruded using temporary anchorage devices to improve the occlusal cant and posterior open bite of the unaffected side. This combined surgical-orthodontic treatment provided a satisfactory outcome without additional orthognathic surgery.

Accuracy assessment of image-based surface meshing for volumetric computed tomography images in the craniofacial region.

BACKGROUND: Three-dimensional printing and computer-assisted surgery demand a high-precision three-dimensional mesh model created from computed tomography (CT) imaging data using an image-based meshing algorithm. We aimed to evaluate the three-dimensional geometric accuracy of surface meshes produced from CT images with commercially available software packages. METHODS: The CT images were acquired for 3 human dry skulls and 10 manufactured plastic skulls. Four commercially available software packages were used to produce the surface meshes in stereolithography (STL) file format. These CT-based STL surface meshes were registered and compared with three-dimensional optical-scanned reference mesh surface for evaluating the accuracy of the STL mesh produced with each software package. RESULTS: The surface geometries produced by the CT-image-based meshing process were all relatively accurate; differences from the three-dimensional optical-scanned data were in the voxel or subvoxel range. However, when comparisons with the three-dimensional optical-scanned surface data were performed in individual anatomic regions, we found significantly different accuracies of the CT-based STL surface meshes produced by the different software packages. CONCLUSIONS: We found that all 4 software packages showed reasonably good meshing accuracies for clinical use. However, the range of errors inherent in the CT-image-based meshing process demands that caution should be taken in selecting and manipulating the software to avoid potential errors in specific clinical applications.

Construction and validation of the midsagittal reference plane based on the skull base symmetry for three-dimensional cephalometric craniofacial analysis.

OBJECTIVE: The objective of this study was to determine the reliable midsagittal (MS) reference plane in practical ways for the three-dimensional craniofacial analysis on three-dimensional computed tomography images. METHODS: Five normal human dry skulls and 20 normal subjects without any dysmorphoses or asymmetries were used. The accuracies and stability on repeated plane construction for almost every possible candidate MS plane based on the skull base structures were examined by comparing the discrepancies in distances and orientations from the reference points and planes of the skull base and facial bones on three-dimensional computed tomography images. RESULTS: The following reference points of these planes were stable, and their distribution was balanced: nasion and foramen cecum at the anterior part of the skull base, sella at the middle part, and basion and opisthion at the posterior part. CONCLUSIONS: The candidate reference planes constructed using the aforementioned reference points were thought to be reliable for use as an MS reference plane for the three-dimensional analysis of maxillofacial dysmorphosis.

Reconstruction of the premaxilla by segmental distraction osteogenesis for maxillary retrusion in cleft lip and palate.

We present a strategy to target one of the main areas causing retruded maxilla, the premaxillary region for patients with cleft lip and palate (CLP). Advancement of the premaxilla by distraction osteogenesis is attempted, and the retruded anterior maxilla, the collapsed dental space, and the arch shape are sufficiently improved. This strategy also prevents deterioration of the velopharyngeal incompetency function. The procedure seems to be a good option for the treatment of maxillary retrusion and malocclusion for CLP.

Transition of endochondral bone formation at the normal and botulinum-treated mandibular condyle of growing juvenile rat.

OBJECTIVE: The aim of this study was to understand the temporal and spatial distribution of canonical endochondral ossification (CEO) and non-canonical endochondral ossification (NCEO) of the normal growing rat condyle, and to evaluate their histomorphological changes following the simultaneous hypotrophy of the unilateral masticatory closing muscles with botulinum toxin (BTX). DESIGN: 46 rats at postnatal 4 weeks were used for the experiment and euthanized at postnatal 4, 8, and 16 weeks. The right masticatory muscles of rats in experimental group were injected with BTX, the left being injected with saline as a control. The samples were evaluated using 3D morphometric, histological, and immunohistochemical analysis with three-dimensional regional mapping of endochondral ossifications. RESULTS: The results showed that condylar endochondral ossification changed from CEO to NCEO at the main articulating surface during the experimental period and that the BTX-treated condyle presented a retroclined smaller condyle with an anteriorly-shifted narrower articulating surface. This articulating region showed a thinner layer of the endochondral cells, and a compact distribution of flattened cells. These were related to the load concentration, decreased cellular proliferation with thin cellular layers, reduced extracellular matrix, increased cellular differentiation toward the osteoblastic bone formation, and accelerated transition of the ossification types from CEO to NCEO. CONCLUSION: The results suggest that endochondral ossification under loading tended to show more NCEO, and that masticatory muscular hypofunction by BTX had deleterious effects on endochondral bone formation and changed the condylar growth vector, resulting in a retroclined, smaller, asymmetrical, and deformed condyle with thin cartilage.

Fully automatic integration of dental CBCT images and full-arch intraoral impressions with stitching error correction via individual tooth segmentation and identification.

We present a fully automated method of integrating intraoral scan (IOS) and dental cone-beam computerized tomography (CBCT) images into one image by complementing each image's weaknesses. Dental CBCT alone may not be able to delineate precise details of the tooth surface due to limited image resolution and various CBCT artifacts, including metal-induced artifacts. IOS is very accurate for the scanning of narrow areas, but it produces cumulative stitching errors during full-arch scanning. The proposed method is intended not only to compensate the low-quality of CBCT-derived tooth surfaces with IOS, but also to correct the cumulative stitching errors of IOS across the entire dental arch. Moreover, the integration provides both gingival structure of IOS and tooth roots of CBCT in one image. The proposed fully automated method consists of four parts; (i) individual tooth segmentation and identification module for IOS data (TSIM-IOS); (ii) individual tooth segmentation and identification module for CBCT data (TSIM-CBCT); (iii) global-to-local tooth registration between IOS and CBCT; and (iv) stitching error correction for full-arch IOS. The experimental results show that the proposed method achieved landmark and surface distance errors of 112.4µm and 301.7µm, respectively.

The validity of marker registration for an optimal integration method in mandibular navigation surgery.

PURPOSE: The aim of this study was to verify the accuracy of 2 registration methods (marker-based registration and marker-free registration) during mandibular navigation surgery. MATERIALS AND METHODS: Two point-to-point registration methods (marker-based registration and marker-free registration) were tested using software and navigation equipment: 1) 3 implanted orthodontic screws and 2) 3 anatomic points on the cusp tips of the teeth (central incisor and first molars bilaterally). RESULTS: For the navigation equipment, the 3-point matching method of screw references was more accurate for all anatomic areas except the coronoid process and second premolar alveolar area. The registration error was largest for the condyle area. Errors were larger than 2.0 mm in the condyle, condyle neck, sigmoid notch, coronoid process, posterior border, lingula, and angle areas. In the oblique ridge, mental foramen, and dentoalveolar areas, the registration error using screws was smaller than 1.5 mm. For the software, tooth cusp references were more accurate for anatomic areas such as the mental foramen and dentoalveolar areas, but not the molar area. In all cases, the registration error was smaller than 1.0 mm, and that for the first molar was similar between the tooth tip overlap and the screw overlap. CONCLUSIONS: Registration using screws generally was more accurate than registration using tooth cusps for mandibular navigation surgery. However, tooth tip references can be used for registration in dentoalveolar surgery.

Morphologic relationship between the cranial base and the mandible in patients with facial asymmetry and mandibular prognathism.

INTRODUCTION: This study was conducted to measure the dimensional changes in the cranial base and the mandible in patients with facial asymmetry and mandibular prognathism, and to examine the morphologic relationship between asymmetries of the cranial base and the mandible. METHODS: The patients were 60 adults with mandibular prognathism, divided into a symmetry group (menton deviation, <2 mm; n = 30) and an asymmetry group (menton deviation, >4 mm; n = 30) according to the degree of menton deviation. Three-dimensional computed tomography scans were obtained with a spiral scanner. Landmarks were designated on the reconstructed 3-dimensional surface models. Linear, angular, and volumetric measurements of the cranial base and mandibular variables were made. RESULTS: In the asymmetry group, the hemi-base, anterior cranial base, and middle cranial base volumes were significantly larger (P <0.01), and crista galli to sphenoid, sphenoid to petrous ridge, anterior clinoid process to petrous ridge, and vomer to petrous ridge lengths were significantly longer (P <0.05) on the nondeviated side than on the deviated side. Menton deviation was significantly correlated with the difference in hemi-base volume, and ramal volume was significantly correlated with the difference in hemi-base and middle cranial base volumes between the nondeviated and deviated sides (P <0.05). CONCLUSIONS: In patients with facial asymmetry and mandibular prognathism, cranial base volume increased on the nondeviated side and was also correlated with mandibular asymmetry.

Metal artifact reduction in CT by identifying missing data hidden in metals.

There is increasing demand in the field of dental and medical radiography for effective metal artifact reduction (MAR) in computed tomography (CT) because artifact caused by metallic objects causes serious image degradation that obscures information regarding the teeth and/or other biological structures. This paper presents a new MAR method that uses the Laplacian operator to reveal background projection data hidden in regions containing data from metal. In the proposed method, we attempted to decompose the projection data into two parts: data from metal only (metal data), and background data in the absence of metal. Removing metal data from the projections enables us to perform sparsity-driven reconstruction of the metal component and subsequent removal of the metal artifact. The results of clinical experiments demonstrated that the proposed MAR algorithm improves image quality and increases the standard of 3D reconstruction images of the teeth and mandible.

Accuracy and validity of stitching sectional cone beam computed tomographic images.

To determine whether three-dimensionally reconstructed images of skulls created by stitching multiple cone beam computed tomographic (CBCT) images are as accurate as single images obtained using multidetector computed tomography (MDCT), 10 skull models were scanned using an optical three-dimensional scanner, MDCT, and CBCT. Cone beam CT images at 3 different levels of the skull were manually superimposed and stitched. The reconstructed CBCT images at each level were aligned and fused using computer software and then compared to the nominal reference image obtained from the optical three-dimensional scanner by determining positional errors. The reconstructed MDCT images were also compared, and the differences in the mean errors for the 3 image types compared with the nominal reference image data were evaluated. There were no significant differences between the MDCT images and the manually merged CBCT images (Wilcoxon signed rank test, P = 0.017). In contrast, there were significant differences between the MDCT images and the software-aligned CBCT images (P = 0.005). Manual stitching of CBCT sectional images at different levels can provide accurate anatomic details of the oral and maxillofacial regions.

Reduction malarplasty using a simulated surgical guide for asymmetric/prominent zygoma.

BACKGROUND: The present study introduces a reduction malarplasty using a three-dimensional (3D)-printed surgical guide and evaluates the guide's technical applicability. METHODS: Twenty malarplasties were performed for 12 subjects with zygomatic asymmetry/prominency using the current method. 3D reconstruction of the craniomaxillofacial region and fine dental occlusion was made with image data from computed tomograpy and dental scanning. A computer-assisted surgical simulation was performed for reduction malarplasty and a surgical guide was designed for later 3D printing. The manufactured surgical guide was introduced to the operation field to guide the surgery; its surgical accuracy was confirmed by comparing five corresponding points from preoperative simulation and postoperative data. RESULTS: We successfully performed the reduction malarplasty with the surgical guide. The accuracy level of surgery fell to 0.93 mm of total median difference for the corresponding zygoma points of preoperative simulations and postoperative zygoma. The anterior and upper points showed less error level (0.59 and 0.73 mm difference, respectively) than did other points. CONCLUSIONS: We developed a computer-assisted surgical technique using a surgical guide for asymmetrical/prominent zygoma which proved to be simple, practical, and accurate; it is expected to help surgeons perform reduction malarplasty with ease and accuracy.

A semi-supervised learning approach for automated 3D cephalometric landmark identification using computed tomography.

Identification of 3D cephalometric landmarks that serve as proxy to the shape of human skull is the fundamental step in cephalometric analysis. Since manual landmarking from 3D computed tomography (CT) images is a cumbersome task even for the trained experts, automatic 3D landmark detection system is in a great need. Recently, automatic landmarking of 2D cephalograms using deep learning (DL) has achieved great success, but 3D landmarking for more than 80 landmarks has not yet reached a satisfactory level, because of the factors hindering machine learning such as the high dimensionality of the input data and limited amount of training data due to the ethical restrictions on the use of medical data. This paper presents a semi-supervised DL method for 3D landmarking that takes advantage of anonymized landmark dataset with paired CT data being removed. The proposed method first detects a small number of easy-to-find reference landmarks, then uses them to provide a rough estimation of the all landmarks by utilizing the low dimensional representation learned by variational autoencoder (VAE). The anonymized landmark dataset is used for training the VAE. Finally, coarse-to-fine detection is applied to the small bounding box provided by rough estimation, using separate strategies suitable for the mandible and the cranium. For mandibular landmarks, patch-based 3D CNN is applied to the segmented image of the mandible (separated from the maxilla), in order to capture 3D morphological features of mandible associated with the landmarks. We detect 6 landmarks around the condyle all at once rather than one by one, because they are closely related to each other. For cranial landmarks, we again use the VAE-based latent representation for more accurate annotation. In our experiment, the proposed method achieved a mean detection error of 2.88 mm for 90 landmarks using only 15 paired training data.

Correlation Analysis between Three-Dimensional Changes in Pharyngeal Airway Space and Skeletal Changes in Patients with Skeletal Class II Malocclusion following Orthognathic Surgery.

INTRODUCTION: Studies on the pharyngeal airway space (PAS) changes using three-dimensional computed tomography (CT) have shed more light on patients with Class III than Class II malocclusion. This paper focuses on analyzing the long-term changes in the PAS and evaluating the postoperative association between these PAS and skeletal changes in patients with skeletal Class II malocclusion who have undergone orthognathic surgery. METHODS: The records of 21 patients with skeletal Class II malocclusion who had undergone orthognathic surgery were included. The anatomical modifications in both jaws, changes in volume, sectional area (SA), minimum sectional area (MSA), and anterior-posterior (AP) and transverse (TV) width in the airway at one month before surgery (T0), and one month (T1) and one year (T2) after surgery were analyzed using CT images. The association between the skeletal and airway changes was evaluated between T0, T1, and T2. RESULTS: After surgery, the ANS, A point, and PNS demonstrated significant posterior and superior movement. The B point and the pogonion exhibited substantial anterior and superior movement. The total and inferior oropharyngeal volumes (vol 3, vol 4) notably increased, while the nasopharyngeal volume (vol 1) decreased. The anterior-posterior movement at the ANS and PNS after surgery was significantly associated with the total volume, vol 2, vol 3, SA 1, MSA, and TV width 1, while substantial association with the total volume was found at the pogonion. CONCLUSION: Thus, an ideal treatment plan can be formulated for patients with skeletal Class II malocclusion by considering the postoperative PAS changes.

Early orthognathic surgery with three-dimensional image simulation during presurgical orthodontics in adults.

To correct dentofacial deformities, three-dimensional skeletal analysis and computerized orthognathic surgery simulation are used to facilitate accurate diagnoses and surgical plans. Computed tomography imaging of dental occlusion can inform three-dimensional facial analyses and orthognathic surgical simulations. Furthermore, three-dimensional laser scans of a cast model of the predetermined postoperative dental occlusion can be used to increase the accuracy of the preoperative surgical simulation. In this study, we prepared cast models of planned postoperative dental occlusions from 12 patients diagnosed with skeletal class III malocclusions with mandibular prognathism and facial asymmetry that had planned to undergo bimaxillary orthognathic surgery during preoperative orthodontic treatment. The data from three-dimensional laser scans of the cast models were used in three-dimensional surgical simulations. Early orthognathic surgeries were performed based on three-dimensional image simulations using the cast images in several presurgical orthodontic states in which teeth alignment, leveling, and space closure were incomplete. After postoperative orthodontic treatments, intraoral examinations revealed that no patient had a posterior open bite or space. The two-dimensional and three-dimensional skeletal analyses showed that no mandibular deviations occurred between the immediate and final postoperative states of orthodontic treatment. These results showed that early orthognathic surgery with three-dimensional computerized simulations based on cast models of predetermined postoperative dental occlusions could provide early correction of facial deformities and improved efficacy of preoperative orthodontic treatment. This approach can reduce the decompensation treatment period of the presurgical orthodontics and contribute to efficient postoperative orthodontic treatments.

3D cephalometric landmark detection by multiple stage deep reinforcement learning.

The lengthy time needed for manual landmarking has delayed the widespread adoption of three-dimensional (3D) cephalometry. We here propose an automatic 3D cephalometric annotation system based on multi-stage deep reinforcement learning (DRL) and volume-rendered imaging. This system considers geometrical characteristics of landmarks and simulates the sequential decision process underlying human professional landmarking patterns. It consists mainly of constructing an appropriate two-dimensional cutaway or 3D model view, then implementing single-stage DRL with gradient-based boundary estimation or multi-stage DRL to dictate the 3D coordinates of target landmarks. This system clearly shows sufficient detection accuracy and stability for direct clinical applications, with a low level of detection error and low inter-individual variation (1.96 ± 0.78 mm). Our system, moreover, requires no additional steps of segmentation and 3D mesh-object construction for landmark detection. We believe these system features will enable fast-track cephalometric analysis and planning and expect it to achieve greater accuracy as larger CT datasets become available for training and testing.

Architectural characteristics of the normal and deformity mandible revealed by three-dimensional functional unit analysis.

The 3D architecture of the mandible contributes to the functional and morphological characteristics of the lower one third of craniofacial region. The mandible has six distinct functional units, and its architecture is the sum of balanced growth of each functional unit and surrounding matrix. A dentofacial deformity (DFD) with malocclusion can be interpreted as their unbalanced growth. In order to characterize the mandibular 3D architecture, we analyzed the 3D reconstructed computed tomography (CT) images in terms of functional units. We evaluated both sides of 30 datasets of 3D CT scans of normal controls (N = 6) and patients with prognathic (N = 17) or retrognathic (N = 7) mandibles. We first identified and evaluated reference points to define mandibular functional units and compared their linear and angular measurements of DFD with normal group. The condylar and body length, the ratio of condyle/coronoid length, and the condylar head axis angle showed the statistically significant differences between groups. From these results, we could define the 3D reference points for functional units and identify the 3D architectural characteristics of DFD mandibles. These models may help us improve diagnosis and treatment planning to let them return to the normal and balanced architecture for DFD.

Three-dimensional computed tomography analysis of mandibular morphology in patients with facial asymmetry and mandibular prognathism.

INTRODUCTION: The purpose of this study was to investigate the dimensional changes in each skeletal unit in the mandibles of patients with facial asymmetry and mandibular prognathism. METHODS: The patients consisted of 50 adults with mandibular prognathism, divided into the symmetry group (n = 20) and the asymmetry group (n = 30) according to the degree of menton deviation. Three-dimensional computed tomography scans were obtained with a spiral computed tomography scanner. Landmarks were designated on the reconstructed 3-dimensional surface models. The lines to represent condylar, coronoid, angular, body, and chin units were used. Ramal and body volumes were measured in the hemi-mandibles. RESULTS: In the asymmetry group, condylar and body unit lengths were significantly longer, and coronoid unit length was significantly shorter on the nondeviated side than on the deviated side (P <0.01). Angular and chin unit lengths were not significantly different between the 2 sides (P >0.05). Ramal volume was significantly greater on the nondeviated side (P <0.01), but body volume was not significantly different between the 2 sides (P >0.05). CONCLUSIONS: Both condylar and body units appeared to contribute to mandibular asymmetry, with a more central role of the condylar unit.