Since its advent in 1931, analysis of lateral cephalometric radiographs has been an important aspect of orthodontic diagnosis and treatment planning. This type of orthodontic analysis provides a quantitative evaluation of the positions of various anatomical structures of the face, including skeletal, dental, and soft tissue features. Cephalometric analysis, however, is a time-consuming process and is not always performed in clinical practice. Cephalometric analysis from Cone-Beam Computed Tomography (CBCT) imaging is particularly cumbersome, requiring both reconstruction of a two-dimensional lateral cephalogram as well as subsequent computer-assisted tracing analysis using a program such as Dolphin. As the use of CBCT continues to become more prominent in orthodontics, methodologies to expedite cephalometric analysis may be valuable in facilitating their use by clinicians. Several different commercially available (e.g. CephX) and proprietary products have been created to analyze cephalometric radiographs using automated artificial intelligence (AI), but the accuracy of these products remains incompletely established. Our study examined the accuracy and workflow impacts of CephX’s ABO analysis directly from CBCT compared to manual reconstruction and tracing by human examiners on 40 CBCT volumes. We hypothesized that automatically generated cephalometric analyses from CBCT volumes would differ significantly from those generated by human examiners, and that workflow time would be statistically significantly decreased in the automated analysis. In contrast, overall workflow time was found to be significantly greater for the CephX software than for the human examiners. Furthermore, our study showed that seven of the eleven measurements in the ABO analysis differed statistically significantly from the human examiners: SNB, ANB, SN-MP, L1-NB, L1-MP, LL to E-Plane, and UL to E-Plane. Nine of the eleven measurements showed average measurement error within clinically acceptable limits, while two showed greater average error than is clinically acceptable – U1-SN and L1-MP were the least accurate measurement in our study. Bland-Altman plots were constructed showing that FMA may show a slight tendency towards greater accuracy at high values, while LL to E-Plane may display a slight tendency to underestimate more frequently at low values and overestimate more frequently at high values. Only one measurement (ANB) showed limits of agreement within the maximum allowed difference; ten out of the eleven variables exceeded the maximum allowed difference. Overall, CephX may offer clinically acceptable performance for most variables in the ABO analysis, but needs further improvement overall, particularly with the inclination of the upper and lower incisors (U1-SN and L1-MP).

The specialty of orthodontics aims to optimize patients’ skeletal and dental relationships, creating a harmonious orofacial complex and improving facial aesthetics and occlusal function. One common orthodontic problem is transverse maxillary constriction. Clinically, a transverse deficiency in the upper jaw presents as a narrow palate, dental crowding, crossbite, or a combination of these findings. If this orthodontic problem is diagnosed during the primary or mixed dentition years, it can be readily corrected with rapid palatal expansion. However, adult patients may also present with transverse maxillary constriction, which at this stage of skeletal maturation, requires more invasive treatment. Two treatment options that can address transverse deficiency in non-growing patients are surgically-assisted rapid palatal expansion (SARPE) and microimplant-assisted-rapid-palatal Expansion (MARPE). The MARPE technique involves the use of a maxillary skeletal expander (MSE) appliance anchored to the maxilla with mini-screws, applying expansile forces directly to the skeleton, rather than distributing them across the palate and dentition. Symmetric mid-palatal sutural separation is the anticipated therapeutic effect; however, midfacial changes may occur at other circummaxillary sutures. MARPE treatment outcomes must be evaluated clinically and radiographically. CBCT is the radiographic imaging modality of choice for patients treated with MARPE because of the effects that occur in all three planes of space. Mid-palatal suture measurements, and an abundance of additional information, can be obtained from 3D imaging analysis. The current evidence base surrounding clinical considerations of MSE placement for MARPE therapy is limited. The primary goal of this study was to assess if the skeletal position of MSE mini-screw/temporary anchorage device (TAD) placement influences the magnitude of mid-palatal suture separation and/or is associated with asymmetric skeletal changes during MARPE therapy, using CBCT imaging. We hypothesized that significant differences in mini-screw angulation relative to the palatal plane and the anteroposterior position of the MSE appliance in the hard palate may be associated with asymmetric mid-palatal suture separation. Subjects were grouped based on magnitude of asymmetric separation at the mid-palatal suture. Circummaxillary suture separation symmetry was compared between groups, along with anteroposterior positioning of the appliance, and mini-screw angulation. Our data analyses showed that the only statistically significant correlation for right and left suture separation occurred at the medial pterygoid plate suture in subjects with symmetric mid-palatal suture separation. Analysis of MSE placement and mini-screw angulation in all subjects revealed that the anteroposterior position of the mini-screws is associated with asymmetric expansion, while TAD angulation was not significant. Our findings provide guidance for clinicians’ placement of the MSE appliance in the hard palate. Careful planning and execution of MARPE therapy is likely to lead to improved predictability of mid-palatal suture separation and subsequent changes to other circummaxillary structures.

Cleft lip with or without cleft palate (CL/P) is one of the most common craniofacial anomalies. Patients with CL/P often require extensive and prolonged orthodontic treatment due the skeletal and dental malocclusions that frequently manifest, making the orthodontic burden of care significant compared to the non-cleft patient. Orthodontic treatment may be required at various stages in their dental and skeletal development, during which orthodontic records must regularly be taken, including cephalometric radiographs. These radiographs allow for analysis of skeletal and dental relationships by relating various anatomical landmarks through linear and angular measurements.

Due to the time-consuming nature of the current computer-aided method, which currently involves an orthodontist locating points of a lateral skull radiograph on a computer monitor, systems have recently been developed to automate the cephalometric process. However, while systems such as CephX have been shown to significantly shorten analyzing time, the accuracy of the measurements is inadequate. Further, radiographs of CL/P-affected patients are often excluded from the sample, as identification of cephalometric landmarks is more complicated due to abnormal anatomy. There is promise that lateral simulated 2D cephalometric projections from CBCTs improve the accuracy of cephalometric measurements over 2D cephalograms.

This study sought to compare the accuracy and analyzing time between web-based fully automated and computer-aided cephalometric analysis of lateral cephalometric images derived from cone-beam computed tomography in unilateral cleft lip and palate-affected patients. Both methods of cephalometric analysis were performed on 36 CBCTs obtained of individuals with unilateral cleft lip and palate in the mixed dentition stage.

Of the 12 measurements obtained, 4 measurements, U1-PP (°), SN-MP (°), U1-SN (°) and U1-NA (mm) were both statistically significant (P<0.05) and had mean differences above the clinically acceptable limit of 2 mm or 2°. The agreement interval fell outside the range of clinical acceptability for every measurement. Results also showed that the automated program took significantly longer than the computer-assisted method to produce a cephalometric analysis.

Based on these results, it is advisable to use CephX for cephalometric analysis in patients with cleft lip and palate only with clinician supervision and intervention. Further development is needed, particularly with regard obtaining measurements involving landmarks that are challenging to identify and those with multiple definitions before completely replacing computerized tracing.

Background: Fibromodulin (FMOD) is a small leucine-rich proteoglycan required for scarless fetal cutaneous wound repair. Interestingly, increased FMOD levels have been correlated with decreased transforming growth factor (TGF)-β1 expression in multiple fetal and adult rodent models. Our previous studies demonstrated that FMOD deficiency in adult animals results in delayed wound closure and increased scar size accompanied by loose package collagen fiber networks with increased fibril diameter. In addition, we found that FMOD modulates in vitro expression and activities of TGF-β ligands in an isoform-specific manner. In this study, we investigated the temporospatial distribution of TGF-β ligands and receptors in both adult FMOD-null and wild-type (WT) mouse wounds to further elucidate how FMOD coordinates TGF-β bioactivity to promote proper cutaneous wound healing.

Methods: Expression profiles of TGF-β ligands and receptors in FMOD-null and WT mice were compared by immunohistochemical staining and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) using a full-thickness, primary intention wound closure model.

Results: During the inflammatory stage, elevated inflammatory infiltration accompanied by increased type I TGF-β receptor levels in individual inflammatory cells was observed in FMOD-null wounds. This increased inflammation was correlated with accelerated epithelial migration during the proliferative stage. On the other hand, significantly more robust expression of TGF-β3 and TGF-β receptors in FMOD-null wounds during the proliferative stage was associated with delayed dermal cell migration and proliferation, which led to postponed granulation tissue formation and wound closure and increased scar size. Compared with WT controls, expression of TGF-β ligands and receptors by FMOD-null dermal cells was markedly reduced during the remodeling stage, which may have contributed to the declined collagen synthesis capability and unordinary collagen architecture.

Conclusion: This study demonstrates that a single missing gene, FMOD, leads to conspicuous alternations in TGF-β ligand and receptor expression at all stages of wound repair in various cell types. Therefore, FMOD critically coordinates temporospatial distribution of TGF-β ligands and receptors in vivo, suggesting that FMOD modulates TGF-β bioactivity in a complex way beyond simple physical binding to promote proper wound healing.

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