Physicochemical and biocompatibility characterisation of a 3D lyophilised platelet-rich fibrin scaffold for cleft lip and palate repair.

Craniofacial bone defects result from various disorders such as trauma, congenital malformations and infections. Cleft lip and palate are the most prevalent congenital craniofacial birth defect in humans. Growth factors (GFs) are soluble proteins secreted by cells that regulate various cellular processes and tissue regeneration. At present, developing three-dimensional scaffolds for delivering GFs to the site of injury has become an important aspect in craniofacial bone regeneration. This study aims to develop a novel 3D bone substitute using lyophilized-platelet-rich fibrin (LyPRF) biocomposite scaffolds for potential application for CLP repair. Collagen (C), bioglass (BG), and LyPRF were used to fabricate a biocomposite (C-BG-LyPRF) scaffold. The physical, chemical, and biocompatibility properties of the scaffold were evaluated. The C-BG-LyPRF scaffold demonstrated a mean pore diameter of 146 µm within a porosity of 87.26%. The FTIR spectra verified the presence of am-ide I, II, and III functional groups. The inorganic phase of the C-BG-LyPRF scaffold was composed of sodium, calcium, silicon, and phosphorus, as determined by EDX analysis. Furthermore, C-BG-LyPRF scaffold was biocompatible with MC3T3-E1 cells in both the Live/Dead and prolif-eration assays. Data demonstrate the developed C-BG-LyPRF scaffold exhibits biomimetic and biocompatibility properties, establishing it as a promising biomaterial for craniofacial regeneration.

Three-dimensional imaging in craniofacial surgery: utilization of a novel 3D mobile application to evaluate the surgical outcomes of a skull recontouring procedure for cephalohematoma.

OBJECTIVE: Cranial abnormalities are common birth defects that frequently alter skull shape and appearance. Despite their prevalence, objective quantification of defect severity pre- and posttreatment is limited. The authors evaluated the ability of MirrorMe3D, a novel 3D mobile iPhone application, to measure changes in the contour of the skull for patients undergoing contouring of a calcified cephalohematoma. METHODS: The heads of two 20-month-old patients with disfiguring right parietal cephalohematomas undergoing a skull recontouring operation were scanned pre- and postsurgery. Four scans of the cranial abnormality were taken throughout the procedure and intraoperative 3D models were generated. Models of the head were overlapped pre- and postsurgery and compared using a depth analyzer built into MirrorMe3D. RESULTS: Depth analysis revealed 6.0-mm and 9.9-mm differences for patients 1 and 2, respectively. Volume analysis revealed 33-cm3 and 85-cm3 differences for patients 1 and 2, respectively. Currently, no standard for quantitative measurement of the surgical outcomes of a skull reconstruction procedure exists. CONCLUSIONS: MirrorMe3D provides an efficient method for monitoring patients with simple topographic scans that create accurate models of the head. The authors show the app's ability to capture the severity of a calcified cephalohematoma and quantify the changes in the contour of the skull before and after surgery.

Botulinum Toxin for the Treatment of Postmenopausal Craniofacial Hyperhidrosis.

Postmenopausal craniofacial hyperhidrosis describes a unique subset of primary focal hyperhidrosis in menopausal woman. This condition can be challenging to treat and may require multiple treatment modalities before patients express satisfaction with the results. Current treatment options for craniofacial hyperhidrosis include oral antimuscarinic agents, topical aluminum chloride powder, and botulinum toxin injections. We present the case of a 68-year-old female with craniofacial hyperhidrosis who did not respond to topical agents and did not tolerate an oral antimuscarinic agent. The patient was successfully treated with 100 units of onabotulinum toxin A along the forehead, frontal hairline, and periauricular scalp and reported significant improvement in symptoms and quality of life as a result. We review the literature describing targeted intradermal injection of botulinum neurotoxin as an alternative to medical therapy for craniofacial hyperhidrosis.

Cost Analysis of Avoiding Gastrostomy Tube in Robin Sequence Neonates that Undergo Mandibular Distraction.

OBJECTIVES/HYPOTHESIS: To evaluate costs associated with perioperative gastrostomy tube (G-tube) placement for neonates with Robin sequence (PRS) that undergo mandibular distraction osteogenesis (MDO). METHODS: Retrospective chart review was performed to examine the medical records of neonates with RS who received treatment at our institution between 2012 and 2021. Patients under 6 months of age that underwent MDO for RS were included. Billing records of hospital costs over a 2-year period were analyzed. RESULTS: The study included 26 total patients with 11 in the MDO-only group, 9 in G-tube after MDO group, and 6 in G-tube before MDO group. There was a significant difference (p < 0.001) in total hospital costs between groups with MDO-only group averaging $119,532 (SD ± $$ \pm $$ 33,503), the G-tube after MDO group averaging $245,315 (SD ± $$ \pm $$ 102,327), and G-tube before MDO group averaging $252,300 (SD ± $$ \pm $$ 84,990). Multiple linear regression was performed controlling for genetic syndrome and birth weight, which still showed a statistically significant difference in total cost between the MDO-only group and G-tube after MDO (p = 0.006), and between the MDO-only group and G-tube prior to MDO (p = 0.01). There was a significant difference in costs between all three groups for total inpatient/outpatient costs with MDO-only group averaging $78,502 (SD ± $$ \pm $$ 30,953), the G-tube after MDO group averaging $176,125 (SD ± $$ \pm $$ 84,315), and the G-tube prior to MDO group averaging $156,309 (SD ± $$ \pm $$ 95,746). CONCLUSIONS: MDO performed without perioperative G-tube placement may reduce charges by >$100,000. The associated improvement of dysphagia after MDO surgery and potential for avoiding a G-tube has tremendous downstream cost and social benefits for families. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

foxe1 mutant zebrafish show indications of a hypothyroid phenotype and increased sensitivity to ethanol for craniofacial malformations.

BACKGROUND: FOXE1 mutations in humans are associated with cleft palate and hypothyroidism. We previously developed a foxe1 mutant zebrafish demonstrating mineralization defects in larvae. In the present study, we investigate the thyroid status and skeletal phenotype of adult foxe1 mutants. RESULTS: Mutant fish have increased expression of tshß in the pituitary, and of hepatic dio1 and dio2. In plasma, we found higher Mg levels. Together these findings are indicative of hypothyroidism. We further observed mineralization defects in scales due to enhanced osteoclast activity as measured by increased expression levels of tracp, ctsk, and rankl. Gene-environment interactions in the etiology of FOXE1-related craniofacial abnormalities remain elusive, which prompts the need for models to investigate genotype-phenotype associations. We here investigated whether ethanol exposure increases the risk of developing craniofacial malformations in foxe1 mutant larvae that we compared to wild types. We found in ethanol-exposed mutants an increased incidence of developmental malformations and marked changes in gene expression patterns of cartilage markers (sox9a), apoptotic markers (casp3b), retinoic acid metabolism (cyp26c1), and tissue hypoxia markers (hifaa, hifab). CONCLUSION: Taken together, this study shows that the foxe1 mutant zebrafish recapitulates phenotypes associated with FOXE1 mutations in human patients and a clear foxe1-ethanol interaction.

Palatal canine impaction is associated with craniofacial shape in humans.

BACKGROUND/OBJECTIVES: It is unclear whether palatal canine impaction is related to genetic or local/environmental factors. If a genetic origin is assumed, then it could be expected that palatal canine impaction is associated with overall craniofacial development. Within this context, the aim of this study was to evaluate the craniofacial morphology of individuals with palatal canine impaction and compare it to a matched group of normal controls. MATERIALS/METHODS: The sample for this investigation comprised 404 individuals (232 females and 172 males). Half of these individuals presented with unilateral or bilateral palatal canine impaction confirmed clinically and radiographically. The other half were matched for sex and age with the first half and comprised individuals without tooth impaction, apart from third molars. The shape of the craniofacial structures was outlined on calibrated cephalometric images through 15 curves and 127 landmarks (11 fixed and 116 semi-landmarks). Shape configurations were superimposed using Procrustes Superimposition and the resulting shape coordinates were reduced into principal components for all subsequent analyses. The effect of palatal canine impaction on craniofacial shape was assessed with regression models, separately in females and males. All statistical tests were performed assuming a type-1 error of 5%. RESULTS: Individuals with palatally impacted canines appear to have a less convex face, a more brachyfacial skeletal pattern, and a sagittally extended premaxilla. In females effect sizes ranged between η2 = 0.136-0.397 (P < 0.05) and in males between η2 = 0.125-0.396 (P < 0.05, apart from the entire craniofacial configuration: P = 0.259). LIMITATIONS: Palatal canine impaction was not confirmed through cone beam computer tomography images in all patients, however, in those cases, the treatment history confirmed the diagnosis. CONCLUSIONS/IMPLICATIONS: Palatal canine impaction is related to a distinct craniofacial shape in females and males. These findings allow for speculation that palatal canine impaction is affected by genetic pathways involved in overall craniofacial development.

Scoping review of qualitative data of patient experience and unmet needs following facial trauma.

Facial trauma is a common presentation to the emergency department, encompassing a spectrum from soft tissue injuries to fractures of the facial skeleton. Beyond the evident physical consequences, patients frequently face significant psychosocial issues, which are often overlooked in the recovery phase of treatment. The purpose of this review was to establish the experiences of patients following facial trauma using qualitative patient-reported data. A scoping review, searching four electronic databases (MEDLINE, Web of Science, PsychINFO, and Cochrane Library) using PRISMA methodology was conducted. Only one paper fulfilled the inclusion criteria. The paper used semi-structured open-ended interviews to obtain 20 patients' experiences of sustaining maxillofacial trauma and then synthesised the qualitative interviews into different themes. The findings from this scoping review highlight the profound need for prospective qualitative research in craniomaxillofacial traumatology, to better understand and address the experiences and perspectives of patients following facial trauma.

Vigilant Fiberoptic Orotracheal Intubation in a Patient With Severe Craniofacial Trauma During the Last Morocco Earthquake.

Maxillofacial trauma is prevalent, particularly among the young population, often stemming from assaults, road accidents, or sports-related mishaps. Traditional intubation methods for managing these injuries can be challenging, especially with occluso-facial fractures requiring intermaxillary blocking for dental articulation restoration. Effective management requires interdisciplinary collaboration between emergency physicians, anesthetists, and maxillofacial surgeons. Proficiency in techniques like the vigilant fiberoptic approach should be emphasized through specialized training courses. This collaborative approach ensures the best possible strategy for managing difficult airways, with input from all stakeholders including patients, students, and practitioners. In this case, we successfully conducted a rapid-sequence awake fiberoptic oral intubation on a trauma patient, during the last earthquake that hit Morocco, with severe craniofacial injuries and an unstable skull. The patient, a 40-year-old woman, presented with complex facial fractures, including hemi lefort III on the right and hemi lefort II on the left, along with minimal subarachnoid hemorrhage and frontal pneumocephalus. Due to the patient's compromised airway from diffuse facial bleeding and low oxygen saturation, we opted for awake fiberoptic intubation once immediate life-threatening issues were addressed. This approach allowed us to maintain the patient's spontaneous respirations and navigate around unstable craniofacial structures. The procedure was performed with meticulous care, considering the patient's unstable skull, and was successful without complications. Post-intubation, the patient was extubated, and her recovery was uneventful.

Transglabellar Butterfly Incision for Anterior Cranial Vault Access: Case Report.

(1) Background: The transglabellar approach, a type of transfacial technique, typically involves glabellar resection and opening the frontal sinus via a bicoronal incision, providing access to the anterior cranial vault. To prevent complications, the frontal sinus is typically obliterated. However, the success of transnasal endoscopic techniques has prompted a re-evaluation of these traditional methods. (2) Methods: This paper provides a brief literature review and discusses the removal of an elongated glioma of the left gyrus rectus (4.4 × 1.9 × 2.2 cm) in a 63-year-old male using a transglabellar subfrontal approach via a butterfly incision, with frontal sinus preservation. (3) Results: An uneventful gross-total resection of a WHO grade II oligodendroglioma was achieved. There is a paucity of literature describing a transglabellar subfrontal approach via a butterfly incision with frontal sinus preservation. (4) Conclusions: The described approach could be utilized in selected cases such as small intra-axial lesions oriented longitudinally along the inferomedial frontal lobe from the posterior wall of the frontal sinus to the anterior communicating artery complex in patients with pre-existing glabellar rhytids. Since this is merely a case presentation, we cannot conclude that this represents established clinical practice. The outcomes of this approach should be investigated in the future.

Craniofacial Imaging of Pediatric Patients by Ultrashort Echo-Time Bone-Selective MRI in Comparison to CT.

RATIONALE AND OBJECTIVES: The emergence of low-dose protocols for CT imaging has mitigated pediatric radiation exposure, yet ionizing radiation remains a concern for children with complex craniofacial conditions requiring repeated radiologic monitoring. In this work, the clinical feasibility of an ultrashort echo time (UTE) MRI sequence was investigated in pediatric patients. MATERIALS AND METHODS: Twelve pediatric patients (6 female, age range 8 to 18 years) with various imaging conditions were scanned at 3T using a dual-radiofrequency, dual-echo UTE MRI sequence. Bright-bone images were generated using a weighted least-squares conjugate gradient method to enhance bone specificity. The overlap of the binary skull masks was quantified using the Dice similarity coefficient (DSC) and the 95th percentile Hausdorff distance (HD95) to evaluate the similarity between MRI and CT. To assess the anatomic accuracy of 3D skull reconstructions, six craniometric distances were recorded and the agreement between MRI- and CT-derived measurements was evaluated using Lin's concordance correlation coefficient (ρc). RESULTS: The bright-bone images from UTE MRI demonstrated high bone-contrast, suppression of soft tissue, and separation from air at the sinuses. The DSC and HD95 between MRI and CT had medians of 0.81 ± 0.10 and 1.87 ± 0.32 mm, respectively. There was good agreement between MRI and CT for all craniometric distances (ρc ranging from 0.90 to 0.99) with a mean absolute difference in measurements of < 2 mm. CONCLUSION: The clinical feasibility of the UTE MRI sequence for craniofacial imaging was demonstrated in a cohort of pediatric patients, showing good agreement with CT in resolving thin bone structures and craniometry.

Challenges and complications in juvenile localized scleroderma: A practical approach.

Juvenile localized scleroderma is characterised by inflammation which drives fibrosis in skin and soft tissues. The more severe subtypes of localized scleroderma such as linear and craniofacial are more common in children. Additionally, extracutaneous involvement is seen in half of all children and is associated with poorer treatment outcomes and health-related quality of life. Evidence for the management of craniofacial and extracutaneous involvement is lacking and therefore poses a challenge to clinicians. This review aims to provide a practical approach to management of these most challenging features of juvenile localized scleroderma through case studies where we present the available evidence, current recommendations and considerations for management.

Fgf8 contributes to the pathogenesis of Nager syndrome.

Nager syndrome (NS, OMIM 154400) is a rare disease characterized by craniofacial and limb malformations due to variants in the gene encoding splicing factor 3B subunit 4 (SF3B4). Although various noncanonical functions of SF3B4 unrelated to splicing have been previously described, limited studies elucidate molecular mechanisms underlying NS pathogenesis. Here we showed that sf3b4-deficient fish displayed craniofacial and segmentation defects associated with suppression of fgf8 levels, which perturbed FGF signaling and neural crest cell (NCC) expression. Our finding also pointed out that oxidative stress-induced apoptosis was prominently detected in sf3b4-deficient fish and may further exaggerate the bone remodeling process. Notably, injection of exogenous FGF8 significantly rescued the demonstrated defects in sf3b4-deficient fish, which further supported the participation of Fgf8 in NS pathogenesis. Overall, our study provides valuable insights into the molecular mechanism underlying developmental abnormalities observed in NS and suggests future therapeutic strategies to protect against the pathogenesis of NS and possibilities for preventing severe outcomes.

Etiology of craniofacial and cardiac malformations in a mouse model of SF3B4-related syndromes.

Pathogenic variants in SF3B4, a component of the U2 snRNP complex important for branchpoint sequence recognition and splicing, are responsible for the acrofacial disorders Nager and Rodriguez Syndrome, also known as SF3B4-related syndromes. Patients exhibit malformations in the head, face, limbs, vertebrae as well as the heart. To uncover the etiology of craniofacial malformations found in SF3B4-related syndromes, mutant mouse lines with homozygous deletion of Sf3b4 in neural crest cells (NCC) were generated. Like in human patients, these embryos had craniofacial and cardiac malformations with variable expressivity and penetrance. The severity and survival of Sf3b4 NCC mutants was modified by the level of Sf3b4 in neighboring non-NCC. RNA sequencing analysis of heads of embryos prior to morphological abnormalities revealed significant changes in expression of genes forming the NCC regulatory network, as well as an increase in exon skipping. Additionally, several key histone modifiers involved in craniofacial and cardiac development showed increased exon skipping. Increased exon skipping was also associated with use of a more proximal branch point, as well as an enrichment in thymidine bases in the 50 bp around the branch points. We propose that decrease in Sf3b4 causes changes in the expression and splicing of transcripts required for proper craniofacial and cardiac development, leading to abnormalities.

Untangling Zebrafish Genetic Annotation: Addressing Complexities and Nomenclature Issues in Orthologous Evaluation of TCOF1 and NOLC1.

Treacher Collins syndrome (TCS) is a genetic disorder affecting facial development, primarily caused by mutations in the TCOF1 gene. TCOF1, along with NOLC1, play important roles in ribosomal RNA transcription and processing. Previously, a zebrafish model of TCS successfully recapitulated the main characteristics of the syndrome by knocking down the expression of a gene on chromosome 13 (coding for Uniprot ID B8JIY2), which was identified as the TCOF1 orthologue. However, database updates renamed this gene as nolc1 and the zebrafish database (ZFIN) identified a different gene on chromosome 14 as the TCOF1 orthologue (coding for Uniprot ID E7F9D9). NOLC1 and TCOF1 are large proteins with unstructured regions and repetitive sequences that complicate alignments and comparisons. Also, the additional whole genome duplication of teleosts sets further difficulty. In this study, we present evidence that endorses that NOLC1 and TCOF1 are paralogs, and that the zebrafish gene on chromosome 14 is a low-complexity LisH domain-containing factor that displays homology to NOLC1 but lacks essential sequence features to accomplish TCOF1 nucleolar functions. Our analysis also supports the idea that zebrafish, as has been suggested for other non-tetrapod vertebrates, lack the TCOF1 gene that is associated with tripartite nucleolus. Using BLAST searches in a group of teleost genomes, we identified fish-specific sequences similar to E7F9D9 zebrafish protein. We propose naming them "LisH-containing Low Complexity Proteins" (LLCP). Interestingly, the gene on chromosome 13 (nolc1) displays the sequence features, developmental expression patterns, and phenotypic impact of depletion that are characteristic of TCOF1 functions. These findings suggest that in teleost fish, the nucleolar functions described for both NOLC1 and TCOF1 mediated by their repeated motifs, are carried out by a single gene, nolc1. Our study, which is mainly based on computational tools available as free web-based algorithms, could help to solve similar conflicts regarding gene orthology in zebrafish.

Maximum mouth opening in patients with cleft lip and palate or craniofacial anomalies compared with non-affected controls: A cross-sectional study.

BACKGROUND: There are limited published data on maximum mouth opening (MMO) for children with cleft lip or palate (CLP) or craniofacial anomalies (CFA). AIM: To report MMO of patients with CLP or CFA compared with non-affected controls. DESIGN: Retrospective cross-sectional review of electronic medical and dental records. Patients with CLP or CFA with recorded MMO, height, and weight were included and compared with a non-affected control individuals seen during orthodontic screening. Outcome measures included MMO, recorded in millimeters of inter-incisal distance, age, height, weight, and sex. RESULTS: Patients with CLP or CFA (n = 376) were matched by age and body mass standardized index (BMIz) to the non-affected pool (n = 376). The affected group had a MMO of 43.14 mm (±7.1 mm) compared with the control group MMO of 48.01 mm (±7.6 mm) with a statistically significant difference of -4.86 mm (p < .0001). Specifically, MMO of the unilateral cleft group is 4.26 mm smaller than that of non-affected controls (p < .0001). MMO of the bilateral cleft group is 3.65 mm smaller than that of non-affected controls (p = 0.0063). CONCLUSIONS: MMO for patients with CLP was significantly smaller as compared to non-affected controls. This study helps establish MMO values for children with CLP and CFA.

Imaging the development of the human craniofacial arterial system - an experimental study.

BACKGROUND: The process of vascular development is essential for shaping complex craniofacial structures. Investigating the interplay between vascular development and orofacial morphogenesis holds critical importance in clinical practice and contributes to advancing our comprehension of (vascular) developmental biology. New insights into specific vascular developmental pathways will have far-reaching implications across various medical disciplines, enhancing clinical understanding, refining surgical techniques, and elucidating the origins of congenital abnormalities. Embryonic development of the craniofacial vasculature remains, however, under-exposed in the current literature. We imaged and created 3-dimensional (D) reconstructed images of the craniofacial arterial system from two early-stage human embryonic samples. OBJECTIVE: The aim of this study was to investigate the vascular development of the craniofacial region in early-stage human embryos, with a focus on understanding the interplay between vascular development and orofacial morphogenesis. MATERIALS AND METHODS: Reconstructions (3-D) were generated from high-resolution diffusible iodine-based contrast-enhanced computed tomography (diceCT) images, enabling visualization of the orofacial arterial system in human embryonic samples of Carnegie stages (CS) 14 and 18 from the Dutch Fetal Biobank, corresponding to weeks 7 and 8.5 of gestation. RESULTS: From two human embryonic samples (ages CS 14 and 18), the vascular development of the orofacial region at two different stages of development was successfully stained with B-Lugol and imaged using a micro-computed tomography (micro-CT) scanner with resolutions of 2.5-µm and 9-µm voxel sizes, respectively. Additionally, educational 3-D reconstructions of the orofacial vascular system were generated using AMIRA 2021.2 software. CONCLUSION: Micro-CT imaging is an effective strategy for high-resolution visualization of vascular development of the orofacial region in human embryonic samples. The generated interactive 3-D educational models facilitate better understanding of the development of orofacial structures.

Relationship between craniofacial skeletal patterns and anatomic characteristics of masticatory muscles: a systematic review and meta-analysis.

BACKGROUND: The anatomic characteristics of the masticatory muscles differ across craniofacial skeletal patterns. OBJECTIVE: To identify differences in the anatomic characteristics of masticatory muscles across different sagittal and vertical craniofacial skeletal patterns. ELIGIBILITY CRITERIA: Studies measuring the thickness, width, cross-sectional area (CSA), volume and orientation of masticatory muscles in healthy patients of different sagittal (Class I, Class II, and Class III) and/or vertical (normodivergent, hypodivergent, and hyperdivergent) patterns. INFORMATION SOURCES: Unrestricted literature searches in 8 electronic databases/registers until December 2023. RISK OF BIAS AND SYNTHESIS OF RESULTS: Study selection, data extraction, and risk of bias assessment with a customised tool were performed independently in duplicate. Random-effects meta-analysis and assessment of the certainty of clinical recommendations with the GRADE approach were conducted. RESULTS: 34 studies (37 publications) were selected with a total of 2047 participants and data from 16 studies were pulled in the meta-analysis. Masseter muscle thickness in relaxation was significantly greater by 1.14 mm (95% CI 0.74-1.53 mm) in hypodivergent compared to normodivergent patients while it was significantly decreased in hyperdivergent patients by - 1.14 mm (95% CI - 1.56 to - 0.73 mm) and - 2.28 mm (95% CI - 2.71 to - 1.85 mm) compared to normodivergent and hypodivergent patients respectively. Similar significant differences were seen between these groups in masseter muscle thickness during contraction as well as masseter muscle CSA and volume. Meta-analyses could not be performed for sagittal categorizations due to insufficient number of studies. CONCLUSIONS: Considerable differences in masseter muscle thickness, CSA and volume were found across vertical skeletal configurations being significantly reduced in hyperdivergent patients; however, results should be interpreted with caution due to the high risk of bias of the included studies. These variations in the anatomic characteristics of masticatory muscles among different craniofacial patterns could be part of the orthodontic diagnosis and treatment planning process. REGISTRATION: PROSPERO CRD42022371187 .

Analysis of Three-Dimensional Tooth Movement: A Comparative Study Between Digital Dental Models and Craniofacial Models.

OBJECTIVE: This study aims to validate the efficacy of using a digital dental model (DM) with reference to the palatal region of interest (PROI) for assessing orthodontic tooth movement (TM) by comparing it with the analysis of a computed tomography (CT) model with reference to the cranial region of interest (CROI). MATERIALS AND METHODS: Thirty-four patients (mean age: 21 years and 11 months) with jaw deformities underwent DM and CT scans before and after presurgical orthognathic treatment. Linear and angular measurements during TM were conducted in three dimensions using both DM and CT to assess reliability. RESULTS: DM analysis with PROI registration exhibited high levels of reproducibility, with minimal standard errors in X, Y, and Z displacements (<0.15 mm) and 0.43 degrees in angular change. CT analysis with CROI registration demonstrates similarly high reproducibility, with standard errors inferior to DM analysis (<0.20 mm). Bland-Altman analysis indicated agreement in linear changes of each X, Y, and Z displacement between DM and CT measurements, with limits of agreement (LOA) below 0.91 mm. CONCLUSIONS: The results of this study suggest that the PROI, focusing on the third palatal rugae and the horizontal part of the palatal vault, serves as a reliable reference region for evaluating three-dimensional (3D) tooth movement. CLINICAL SIGNIFICANCE: Digital dental models offer distinct advantages including the absence of X-ray exposure, no metal artifacts, and the ability to generate high-resolution 3D models. The methodology demonstrated high precision and reproducibility, supporting its potential clinical utility in orthodontic treatment planning and assessment.

Deciphering the spatial distribution of Gli1-lineage cells in dental, oral, and craniofacial regions.

The craniofacial bone, crucial for protecting brain tissue and supporting facial structure, undergoes continuous remodeling through mesenchymal (MSCs) or skeletal stem cells (SSCs) in their niches. Gli1 is an ideal marker for labeling MSCs and osteoprogenitors in this region, and Gli1-lineage cells are identified as pivotal for bone growth, development, repair, and regeneration. Despite its significance, the distribution of Gli1-lineage cells across the dental, oral, and craniofacial (DOC) regions remains to be systematically explored. Utilizing tissue-clearing and light sheet fluorescence microscopy (LSFM) with a Gli1CreER; tdTomatoAi14 mouse model, we mapped the spatial distribution of Gli1-lineage cells throughout the skull, focusing on calvarial bones, sutures, bone marrow, teeth, periodontium, jaw bones, and the temporomandibular joint (TMJ). We found Gli1-lineage cells widespread in these areas, underscoring their significance in DOC regions. Additionally, we observed their role in repairing calvarial bone defects, providing novel insights into craniofacial biology and stem cell niches and enhancing our understanding of stem cells and their progeny's behavior in vivo.

This study investigates the presence and role of a specific stem cell population, known as Gli1-lineage cells, in various parts of the skull and facial bones. Using advanced imaging techniques, we found that these cells are widely distributed across the dental, oral, and craniofacial regions, especially in the cranial sutures, teeth, and jaw. Notably, Gli1-lineage cells migrate to the injury site, which is essential in bone repair and regeneration. These findings enhance our understanding of how stem cells contribute to healing and development in the craniofacial region.

Three contrasts in 3 min: Rapid, high-resolution, and bone-selective UTE MRI for craniofacial imaging with automated deep-learning skull segmentation.

PURPOSE: Ultrashort echo time (UTE) MRI can be a radiation-free alternative to CT for craniofacial imaging of pediatric patients. However, unlike CT, bone-specific MR imaging is limited by long scan times, relatively low spatial resolution, and a time-consuming bone segmentation workflow. METHODS: A rapid, high-resolution UTE technique for brain and skull imaging in conjunction with an automatic segmentation pipeline was developed. A dual-RF, dual-echo UTE sequence was optimized for rapid scan time (3 min) and smaller voxel size (0.65 mm3). A weighted least-squares conjugate gradient method for computing the bone-selective image improves bone specificity while retaining bone sensitivity. Additionally, a deep-learning U-Net model was trained to automatically segment the skull from the bone-selective images. Ten healthy adult volunteers (six male, age 31.5 ± 10 years) and three pediatric patients (two male, ages 12 to 15 years) were scanned at 3 T. Clinical CT for the three patients were obtained for validation. Similarities in 3D skull reconstructions relative to clinical standard CT were evaluated based on the Dice similarity coefficient and Hausdorff distance. Craniometric measurements were used to assess geometric accuracy of the 3D skull renderings. RESULTS: The weighted least-squares method produces images with enhanced bone specificity, suppression of soft tissue, and separation from air at the sinuses when validated against CT in pediatric patients. Dice similarity coefficient overlap was 0.86 ± 0.05, and the 95th percentile Hausdorff distance was 1.77 ± 0.49 mm between the full-skull binary masks of the optimized UTE and CT in the testing dataset. CONCLUSION: An optimized MRI acquisition, reconstruction, and segmentation workflow for craniofacial imaging was developed.