Non-surgical Management of a Large Periapical Lesion: A Case Study of the Successful Application of a Modified Triple Antibacterial Paste.

Infection of the dental pulp involves mainly Gram-negative, anaerobic bacterial flora and due to this infection, the periapical area experiences an immunological response, which is termed a periapical lesion. This lesion may appear as a radiolucent (dark) area on X-rays, which indicates periapical inflammation and infection. Its prevalence depends on factors such as age, oral health maintenance, and dental care. Men are more likely to be affected by this infection than women. There are two modalities for the treatment of periapical lesions: surgical or non-surgical endodontic therapy. The modified triple antibiotic paste (TAP) comprising ciprofloxacin, metronidazole, and clindamycin in the ratio of 1:1:1 was first prepared expressly to treat the teeth with necrotic pulp and to support the protocol for revitalization and regrowth. The treatment was very successful in eliminating germs from the root canal system. It provides broad-spectrum antimicrobial activity against a wide range of bacteria commonly associated with endodontic infections. The modified TAP is usually inserted into the canal for a predetermined amount of time and then removed followed by the irrigation of root canal, which helps to eliminate the microorganisms from the root canal. The non-surgical treatment should always be the first choice over the surgical approach so as to avoid a more invasive procedure.

Influence of periapical lesion volume on the radiodensity of surrounding bone: A CBCT study.

Aim: This study assesses if the size of periapical lesions has an effect on the bone immediately peripheral to an apical lesion. Methods: Cone-beam computed tomography (CBCT) images of 271 periapical lesions were analyzed using Mimics Research™ to determine the CBCT periapical lesion volume index (CBCTPAVI) score, along with the radiodensity of the lesion, lesion border, and surrounding bone in 0.5 mm increments up to 2.0 mm peripheral to the apical lesion. The one-way analysis of variance was used to assess for significant differences in the radiodensity of the lesion, border, and peripheral bone, as well as differences among CBCTPAVI scores. Results: The radiodensity of bone peripheral to the apical lesion increased significantly up to 1.0 mm around the lesion's perimeter. In addition, lesions with higher CBCTPAVI scores showed a significantly greater difference in the radiodensity from the lesion to the lesion border and the peripheral bone, compared to lesions with smaller CBCTPAVI scores. Conclusions: This study for the first time shows the influence of periapical lesion size on the radiodensity of bone peripheral to an apical lesion. Variations in radiodensity at the perimeter of a periapical lesion can be influenced by the size of the lesion, possibly indicating differences in defense response. Knowledge of these phenomena may provide information on bone healing and enhance our understanding of bone peripheral to a periapical lesion.

Comparing the accuracy of two machine learning models in detection and classification of periapical lesions using periapical radiographs.

BACKGROUND: Previous deep learning-based studies were mainly conducted on detecting periapical lesions; limited information in classification, such as the periapical index (PAI) scoring system, is available. The study aimed to apply two deep learning models, Faster R-CNN and YOLOv4, in detecting and classifying periapical lesions using the PAI score from periapical radiographs (PR) in three different regions of the dental arch: anterior teeth, premolars, and molars. METHODS: Out of 2658 PR selected for the study, 2122 PR were used for training, 268 PR were used for validation and 268 PR were used for testing. The diagnosis made by experienced dentists was used as the reference diagnosis. RESULTS: The Faster R-CNN and YOLOv4 models obtained great sensitivity, specificity, accuracy, and precision for detecting periapical lesions. No clear difference in the performance of both models among these three regions was found. The true prediction of Faster R-CNN was 89%, 83.01% and 91.84% for PAI 3, PAI 4 and PAI 5 lesions, respectively. The corresponding values of YOLOv4 were 68.06%, 50.94%, and 65.31%. CONCLUSIONS: Our study demonstrated the potential of YOLOv4 and Faster R-CNN models for detecting and classifying periapical lesions based on the PAI scoring system using periapical radiographs.

Root canal therapy used in conjunction with follow-ups for the nonsurgical handling of an enormous periapical lesion of endodontic origin: Clinical case record.

Key Clinical Message: The main objective of root canal therapy is to locate all the canals, cleaning, and shaping, and obturation to obtain fluid tight seal and to heal the periapical lesion if present. Abstract: The proper cleaning, shaping, and disinfection of the pulp chambers, as well as the filling of the canals, are critical to the efficacy of treatment with root canals. The success of an endodontically treated tooth is dependent on the accuracy of the diagnosis, disinfection, cleaning and shaping, obturation, and finally, the prosthetic rehabilitation management. Root canal therapy should provide a hermatic as well as fluid impenetrable seal which prevents the progression of periapical infection. There are two ways to treat such lesions: surgical and nonsurgical methods. If the root canal is cleaned, shaped, and sealed properly and adequately without the use of a surgical procedure, these lesions will recover during nonsurgical root canal therapy. This case series focuses primarily on the nonsurgical treatment of an enormous periapical lesion and provides evidence that these lesions respond well without surgery.

Comparison of Immediate Implantation into the Socket with and without Periapical Pathology: Systematic Review and Meta-Analysis.

Background and Objectives: The present systematic review and meta-analysis were conducted to evaluate and compare the long-term clinical outcomes of immediate implants placed into fresh sockets with and without periapical pathology. Materials and Methods: After the search and review of the literature in the electronic databases, 109 publications were achieved. The titles and abstracts of 66 publications were screened. After the evaluation of the full text of 22 publications, based on the inclusion criteria, six controlled clinical studies were included in this systematic review and meta-analysis. Results: The statistical calculation showed no heterogeneity among the studies included. The implant survival was 99.6% in the test (socket with periapical pathology) and control (socket without periapical pathology) groups of all the clinical trials. The results of the meta-analysis showed no statistically significant difference between test and control groups regarding the marginal bone level and the width of keratinized mucosa in all the studies. Other parameters indicating plaque level, bleeding on probing, and gingival recession also did not differ between test and control groups at the final follow-up in nearly all studies. Conclusions: Within the limitation of this systemic review and meta-analysis, the obtained data suggest that implants immediately placed into the extraction sockets of teeth exhibiting periapical pathology can be successfully osseointegrated for an extended period.

Anterior Palatal Radicular Cyst: A Case Report.

The most prevalent kind of odontogenic cysts is radicular cysts, which usually develop from the epithelial remnants in the periodontal ligament as a result of inflammation that follows pulp necrosis. We report a case of a 49-year-old male patient who complained of painless swelling in the maxillary anterior region, which turned out to be a radicular cyst. Upon clinical examination, a soft, nontender swelling that fluctuated was found. A periapical lesion was found upon radiographic assessment. A radicular cyst was tentatively diagnosed based on clinical and radiological features. The treatment plan included enucleation, restoration of the defect with bone graft, and endodontic therapy with antibiotics. Endodontic therapy was administered after the cystic lesion was surgically removed. The diagnosis of a radicular cyst was validated by histopathological analysis. The significance of a multidisciplinary approach for the successful management of radicular cysts is emphasized in this case report, which also underscores the need for a comprehensive clinical and radiographic evaluation for accurate diagnosis. Prompt identification and suitable intervention are essential to avert possible complications and guarantee successful treatment results.

Periapical lesion-derived decellularized extracellular matrix as a potential solution for regenerative endodontics.

Pulp regeneration remains a crucial target in the preservation of natural dentition. Using decellularized extracellular matrix is an appropriate approach to mimic natural microenvironment and facilitate tissue regeneration. In this study, we attempted to obtain decellularized extracellular matrix from periapical lesion (PL-dECM) and evaluate its bioactive effects. The decellularization process yielded translucent and viscous PL-dECM, meeting the standard requirements for decellularization efficiency. Proteomic sequencing revealed that the PL-dECM retained essential extracellular matrix components and numerous bioactive factors. The PL-dECM conditioned medium could enhance the proliferation and migration ability of periapical lesion-derived stem cells (PLDSCs) in a dose-dependent manner. Culturing PLDSCs on PL-dECM slices improved odontogenic/angiogenic ability compared to the type I collagen group. In vivo, the PL-dECM demonstrated a sustained supportive effect on PLDSCs and promoted odontogenic/angiogenic differentiation. Both in vitro and in vivo studies illustrated that PL-dECM served as an effective scaffold for pulp tissue engineering, providing valuable insights into PLDSCs differentiation. These findings pave avenues for the clinical application of dECM's in situ transplantation for regenerative endodontics.

Non-surgical Management of Periapical Lesions With the Use of Newer Modalities in Adjunct to the Conventional: A Case Series.

For endodontic therapy to be successful, the root canal space must be sterilized. This is often done using intracanal irrigants and medications. To accomplish periradicular region sterilization and healing, various intracanal medicaments and irrigation techniques have been researched for better treatment outcomes. Ozonated olive oil is the most researched and successful adjunct to other medicaments owing to its antibacterial properties. Triple antibiotic paste (TAP) (metronidazole, ciprofloxacin, and minocycline) was incorporated as an inter-appointment intracanal dressing. Currently, many newer advances are depicting synergistic effects in the elimination of persistent endodontic pathogens. Given this, in the current case series, periapical lesions were managed non-surgically for alternating weeks by the advent of triple antibiotic paste (TAP) and ozonated olive oil (O3-oil) with laser activation. Irrigation and its effects were further enhanced with the use of a laser, aiming for thorough debridement and rendering the canal free of microbes. Once the patient was asymptomatic and there was no sinus drainage seen, final obturation was done. Therefore, this case series depicts that traditional root canal therapy with the use of ozonated olive oil and laser activation can non-surgically heal the lesion, leading to successful treatment outcomes. Periapical lesions in three cases have been observed; on the initial visit, all lesions were accessible, cleansed, and shaped. We administered ozonated olive oil with laser activation and a triple antibiotic paste on the following visit. In all three cases, six-month follow-ups have shown evidence of a successful course of therapy.

Platelet-rich fibrin as an apical barrier for MTA placement in the treatment of teeth with open apices: a pilot study.

OBJECTIVE: The aim of the present pilot study was to assess the effectiveness of the platelet-rich fibrin (PRF) apical barrier for the placement of MTA for the treatment of teeth with periapical lesions and open apices. METHODS: A total of thirty teeth on twenty-eight patients with open apices and periapical periodontitis were enrolled and divided into two groups in the present pilot study. In the PRF group (fourteen teeth in thirteen patients), nonsurgical endodontic treatment was performed using PRF as an apical matrix, after which the apical plug of the MTA was created. For the non-PRF group (fourteen teeth in fourteen patients), nonsurgical endodontic therapy was performed using only the MTA for an apical plug with no further periapical intervention. Clinical findings and periapical digital radiographs were used for evaluating the healing progress after periodic follow-ups of 1, 3, 6, and 9 months. The horizontal dimension of the periapical lesion was gauged, and the changes in the dimensions were recorded each time. The Friedman test, Dunn-Bonferroni post hoc correction, and Mann-Whitney U test were used for statistical analysis, with P < 0.05 serving as the threshold for determining statistical significance. RESULTS: All patients in both groups in the present pilot study had no clinical symptoms after 1 month, with a significant reduction in the periapical lesion after periodic appointments. The lesion width of the PRF group was significantly smaller than that of the non-PRF group in the sixth and ninth month after treatment. CONCLUSIONS: PRF is a promising apical barrier matrix when combined with MTA for the treatment of teeth with open apices and periapical periodontitis. Small number of study subjects and the short time of follow-up period limit the generalizability of these results. TRIAL REGISTRATION: TCTR, TCTR20221109006. Registered 09 November 2022 - Retrospectively registered, https://www.thaiclinicaltrials.org/show/TCTR20221109006 .

Periapical Lesions in Panoramic Radiography and CBCT Imaging-Assessment of AI's Diagnostic Accuracy.

Background/Objectives: Periapical lesions (PLs) are frequently detected in dental radiology. Accurate diagnosis of these lesions is essential for proper treatment planning. Imaging techniques such as orthopantomogram (OPG) and cone-beam CT (CBCT) imaging are used to identify PLs. The aim of this study was to assess the diagnostic accuracy of artificial intelligence (AI) software Diagnocat for PL detection in OPG and CBCT images. Methods: The study included 49 patients, totaling 1223 teeth. Both OPG and CBCT images were analyzed by AI software and by three experienced clinicians. All the images were obtained in one patient cohort, and findings were compared to the consensus of human readers using CBCT. The AI's diagnostic accuracy was compared to a reference method, calculating sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and F1 score. Results: The AI's sensitivity for OPG images was 33.33% with an F1 score of 32.73%. For CBCT images, the AI's sensitivity was 77.78% with an F1 score of 84.00%. The AI's specificity was over 98% for both OPG and CBCT images. Conclusions: The AI demonstrated high sensitivity and high specificity in detecting PLs in CBCT images but lower sensitivity in OPG images.

The effects of NLRP3 inflammasome inhibition or knockout in experimental apical periodontitis induced in mice.

OBJECTIVE: To evaluate the effects of NLRP3 inflammasome inhibition or knockout in experimental apical periodontitis (AP) induced in mice. METHODS: The experimental AP was induced by pulpal exposure. To evaluate NLRP3-specific inhibitor medication (MCC950), WT mice received intraperitoneal injections, while the control received PBS (n = 10). In addition, to evaluate NLRP3 knockout, 35 wild-type (WT) and 35 NLRP3-/- mice were divided into a control group (without pulpal exposure, n = 5) and three experimental groups: after 2, 14 and 42 days after pulpal exposure (n = 10). Microscopic and molecular analyzes were carried out using a significance level of 5%. RESULTS: Exposure to MCC950 did not affect the periapical lesion size after 14 days (P = 0.584). However, exposed mice had a lower expression of IL-1ß, IL-18 and caspase-1 (P = 0.010, 0.016 and 0.002, respectively). Moreover, NLRP3-/- mice showed a smaller periapical lesion after 14 and 42 days (P = 0.023 and 0.031, respectively), as well as a lower expression of IL-1ß after 42 days (P < 0.001), of IL-18 and caspase-1 after 14 (P < 0.001 and 0.035, respectively) and 42 days (P = 0.002 and 0.002, respectively). NLRP3-/- mice also showed a lower mRNA for Il-1ß, Il-18 and Casp1 after 2 (P = 0.002, 0.036 and 0.001, respectively) and 14 days (P = 0.002, 0.002 and 0.001, respectively). CONCLUSIONS: NLRP3 inflammasome inhibition or knockout can attenuate the inflammatory events that result in the periapical lesion (AP) formation after pulpal exposure in mice. CLINICAL RELEVANCE: The NLRP3 inflammasome may be a therapeutic target for AP, and new approaches may verify the impact of its inhibition (through intracanal medications or filling materials) on the bone repair process and treatment success.

Comparative Analysis of Examination Methods for Periapical Lesion Diagnostics: Assessing Cone-Beam Computer Tomography, Ultrasound, and Periapical Radiography.

INTRODUCTION: Periapical lesions of teeth are typically evaluated using periapical X-rays (PA) or cone-beam computer tomography (CBCT); however, ultrasound imaging (US) can also be used to detect bone defects. A comparative analysis is necessary to establish the diagnostic accuracy of US for the detection of periapical lesions in comparison with PA and CBCT. OBJECTIVES: This study aimed to evaluate and compare the measurement precision of US against PA and CBCT in detecting periapical lesions. METHODS: This study included 43 maxillary and mandibular teeth with periapical lesions. All teeth were examined clinically, radiographically, and ultrasonographically. Observers evaluated and measured the periapical lesions on CBCT, PA, and US images. RESULTS: The comparison of lesion size showed that it differs significantly between the different methods of examination. A statistically significant difference was found between CBCT and US (mean difference = 0.99 mm, 95% CI [0.43-1.55]), as well as between CBCT and PA (mean difference = 0.61 mm, 95% CI [0.17-1.05]). No difference was found between the US and PA methods (p = 0.193). CONCLUSION: US cannot replace PA radiography in detecting pathologies but it can accurately measure and characterize periapical lesions with minimal radiation exposure. CBCT is the most precise and radiation-intensive method so it should only be used for complex cases.

Efficacy of Mineral Trioxide Aggregate (MTA) as a Reparative Material in Iatrogenic Furcal Perforations in Mandibular Molars.

BACKGROUND/OBJECTIVES:  Mineral trioxide aggregate (MTA) is widely recognized as one of the most biocompatible materials for perforation repairs during root canal treatment (RCT). Experimental evidence has consistently demonstrated MTA's superior sealing ability and biocompatibility compared to various dental materials, including amalgam, intermediate restorative material, zinc oxide eugenol cement, and resin-modified glass ionomer cement. This study aimed to assess the efficacy of MTA as a reparative material in iatrogenic furcal perforations during RCT. MATERIALS & METHODS: A descriptive cross-sectional study was conducted from May 18, 2021, to November 17, 2021, at the Department of Operative Dentistry, Nishtar Institute of Dentistry, Multan, Pakistan. Seventy-six patients aged 18-60 years, of both genders, who developed iatrogenic furcal perforations during procedures were included. Patients with fractures or endo-perio lesions identified during clinical and radiographic examinations were excluded. Isolation was achieved using a rubber dam. The perforation site was cleaned and irrigated with 1% sodium hypochlorite to control hemorrhage and enhance visualization. Following the manufacturer's recommendations, the perforation site was sealed with MTA mixed with sterile saline. RESULTS: The age range in this study was 18 to 60 years, with a mean age of 42.09 ± 9.69 years. Most patients (56.78%) were between 41-60 years old. Out of the 76 patients, 46 (60.53%) were male, and 30 (39.47%) were female, resulting in a male-to-female ratio of 1.5:1. The study found that MTA's efficacy as a reparative material in iatrogenic furcal perforations was observed in 61 (80.26%) patients. A 6-month follow-up revealed no periodontal ligament breakdown, demonstrating the efficacy of MTA as a reparative material in iatrogenic furcal perforations. CONCLUSION: This study concludes that the efficacy of MTA as a reparative material in iatrogenic furcal perforations is remarkable and significant.

Reprint of: The Effect of Mineral Trioxide Aggregate Obturation Levels on the Outcome of Endodontic Retreatment: An Observational Study.

INTRODUCTION: No clinical studies have examined the effect of mineral trioxide aggregate (MTA) obturation levels on the outcome of endodontic retreatment. This retrospective study examined treatment outcomes in three cohorts that compared overfilling, flush filling, and underfilling after orthograde retreatment using MTA. METHODS: Two hundred fifty patients with 264 teeth diagnosed with previously treated root canals and apical periodontitis retreated in a private endodontic practice were included. All teeth received MTA obturation and the extent of the final filling level was measured in relation to the major apical foramen. After 6-month follow-ups, all nonhealing cases were treated surgically. After 24- to 72-month reviews, the effect of preoperative lesion size and the degree of MTA obturation level were assessed. Multiple linear regression and time-to-event analysis using Stata 17 software (StataCorp LLC, College Station, TX) were used to evaluate the data. RESULTS: Within the three cohorts, 99 out of 108 overfilled teeth (91.7%), 90 out of 103 flush fills (87.4%), and 10 out of 53 underfilled teeth (18.9%) healed and were successfully retreated without surgery at 48-months. When surgical outcomes were included, the combined healed proportion was 93.2%. Preoperative lesion size was found to be an important predictor for retreatment nonhealing. A 1-mm increase in lesion size at baseline resulted in an estimated 11% (95% CI 1.04, 1.18)-38% (95% CI 1.22, 1.58) increase in the risk of surgery. Compared to overfilling and flush filling, underfilling was associated with an approximately three-fold increase in requiring surgery and characterized by delayed healing. CONCLUSION: MTA obturation is a viable retreatment option for teeth with nonhealing endodontic treatment. MTA overfills or flush fillings do not adversely affect healing outcomes. However, MTA underfilling increases the chances for nonhealing and surgical intervention.

Evaluation of stress distribution on an endodontically treated maxillary central tooth with lesion restored with different crown materials: A finite element analysis.

Objectives: The biomechanical response of teeth with periapical lesions that have been restored using various substructure materials, as well as the stress mapping in the alveolar bone, has not been thoroughly described. In this context, the objective of this study is to investigate the structural stress distributions on root canal-treated maxillary right central incisors with lesions restored using different crown materials under linear static loading conditions through finite element analysis (FEA). Methods: In the study, five FEA models were utilised to represent healthy teeth and teeth restored with different substructure materials: (A) a healthy tooth, (B) a lesioned, root canal-treated, composite-filled tooth, (C) a lesioned, fiber-posted, zirconia-based crown, (D) a tooth with lesions, a fiber post, and Ni-Cr infrastructure crown, (E) a tooth with a lesion, a fiber post, and an IPS E-max infrastructure crown. A force of 100 N was applied at an angle of 45° to the long axis of the tooth from 2 mm cervical to the incisal line on the palatal surface. Deformation behaviour and maximum equivalent stress distributions on the tooth sub-components, including the bony structure for each model, were simulated. Results: Differences were observed in the stress distributions of the models. The maximum stress values of the models representing the restorations with different infrastructures varied, and the highest value was obtained in the model of the E-max crown (Model E: 136.050 MPa). The minimum stress magnitudes were obtained from Model B the composite-filled tooth (80.39 MPa); however, it was observed that the equivalent stresses in all the models showed a similar distribution for all components with varying magnitudes. In periapical lesion areas, low stresses were observed. In all models, the cervicobuccal collar region of the teeth had dense equivalent stresses. Conclusion: Different restorative treatment methods applied to root canal-treated teeth with periapical lesions can impact the stress in the alveolar bone and the biomechanical response of the tooth. Relatively high stress values in the cortical bone at the cervical line of the tooth have been observed to decrease towards the apical region. This observation may suggest a potential healing effect by reducing pressure in the periapical lesion area. Clinical significance: Composite resin restorations can be considered the first-choice treatment option for the restoration of root canal-treated teeth with lesions. In crown restorations, it would be advantageous to prefer zirconia or metal-supported prostheses in terms of biomechanics.

Solitary bone plasmacytoma mimicking a lesion of odontogenic origin: A case report.

INTRODUCTION AND IMPORTANCE: Solitary bone plasmacytoma (SBP) is an early-stage plasma cell malignancy. It is an extremely rare condition and its diagnosis may not be straightforward. This report presents a case of maxillary SBP. CASE PRESENTATION: A 48-year old man sought care for persistent swelling and pain in the periapical region of the left maxillary molars. He had been diagnosed with "apical periodontitis" and root canal treatment of teeth #26 and #27 was ineffective. Extra-oral examination revealed swelling at the left maxilla. Intraoral examination revealed a hard, non-fluctuant swollen region in the buccal alveolar mucosa adjacent to the apices of teeth #25-27. Cone-beam computed tomography revealed extensive bone destruction in the left maxilla. The patient underwent partial maxillary resection and radical maxillary sinusotomy. Further testing (positron emission CT scan, histopathological and immunohistochemical examination) confirmed the diagnosis of SBP. The patient had a recurrence two years later, which was managed with left subtotal maxillectomy and radiotherapy. There was no evidence of recurrence during 20 months of follow-up. DISCUSSION: SBP may mimic an odontogenic lesion when found in the jaw bone. To confirm the diagnosis, routine blood test, complete body skeletal survey, metastatic investigations and histopathology should be performed. Radiotherapy is the primary treatment. CONCLUSION: SBP may occur in the maxilla mimicking an odontogenic lesion. Surgery may be part of the diagnostic procedure and an adjunct to definitive radiation. Radiotherapy is the primary treatment.

TLR2 agonist prevents the progression of periapical lesions in mice by reducing osteoclast activity and regulating the frequency of Tregs.

AIM: To evaluate the role of regulatory T lymphocytes (Tregs) in the presence or absence of the synthetic ligand Pam3Cys during the progression of periapical lesion in wild-type (WT) and toll-like receptor 2 knockout (TLR2KO) mice. METHODOLOGY: A total of 130 C57BL/6 male WT and TLR2KO mice were allocated into control (n = 5) and experimental (periapical lesion induction) (n = 10) groups. In specific groups (WT+Pam3cys and TLR2KO+Pam3cys), the synthetic ligand Pam3cys was administered intraperitoneally every 7 days, according to the experimental period (14, 21 and 42 days). At the end of those periods, the animals were euthanized, and the mandible and the spleen were submitted to histotechnical processing. Mandible histological sections were analysed by haematoxylin and eosin, TRAP histoenzymology and immunohistochemistry (FOXP3, RANK, RANKL and OPG). Spleen sections were analysed by immunohistochemistry (FOXP3). RESULTS: The inflammatory infiltrate and bone resorption were more intense in the TLR2KO group compared to the WT group. The animals that received the Pam3cys had smaller periapical lesions when compared to the animals that did not receive the ligand (p < .05). TLR2KO animals showed a significant increase in the number of osteoclasts when compared to TLR2KO+Pam3cys group (p < .05). At 21 days, the WT+Pam3cys group had a lower number of osteoclasts when compared to the WT animals (p = .02). FOXP3 expression was more intense in the WT+Pam3cys groups when compared to the WT animals in the 42 days (p = .03). In the spleen analysis, the WT+Pam3cys group also had a higher expression of FOXP3 when compared to the WT animals at 14 and 42 days (p = .02). Concerning RANKL, there was a reduction in staining in the KOTLR2+Pam3cys groups at 21 and 42 days (p = .03) and a higher binding ratio between RANK/RANKL in animals that did not receive the ligand. CONCLUSION: Administration of the Pam3cys increased the proliferation of Tregs, showed by FOXP3 expression and prevented the progression of the periapical lesion in WT mice. On the other hand, in the TLR2KO animals, Treg expression was lower with larger areas of periapical lesions. Finally, systemic administration of the Pam3cys in KO animals was able to limit the deleterious effects of the absence of the TLR2 receptor.

Uncertainty-based Active Learning by Bayesian U-Net for Multi-label Cone-beam CT Segmentation.

INTRODUCTION: Training of Artificial Intelligence (AI) for biomedical image analysis depends on large annotated datasets. This study assessed the efficacy of Active Learning (AL) strategies training AI models for accurate multilabel segmentation and detection of periapical lesions in cone-beam CTs (CBCTs) using a limited dataset. METHODS: Limited field-of-view CBCT volumes (n = 20) were segmented by clinicians (clinician segmentation [CS]) and Bayesian U-Net-based AL strategies. Two AL functions, Bayesian Active Learning by Disagreement [BALD] and Max_Entropy [ME], were used for multilabel segmentation ("Lesion"-"Tooth Structure"-"Bone"-"Restorative Materials"-"Background"), and compared to a non-AL benchmark Bayesian U-Net function. The training-to-testing set ratio was 4:1. Comparisons between the AL and Bayesian U-Net functions versus CS were made by evaluating the segmentation accuracy with the Dice indices and lesion detection accuracy. The Kruskal-Wallis test was used to assess statistically significant differences. RESULTS: The final training set contained 26 images. After 8 AL iterations, lesion detection sensitivity was 84.0% for BALD, 76.0% for ME, and 32.0% for Bayesian U-Net, which was significantly different (P < .0001; H = 16.989). The mean Dice index for all labels was 0.680 ± 0.155 for Bayesian U-Net and 0.703 ± 0.166 for ME after eight AL iterations, compared to 0.601 ± 0.267 for Bayesian U-Net over the mean of all iterations. The Dice index for "Lesion" was 0.504 for BALD and 0.501 for ME after 8 AL iterations, and at a maximum 0.288 for Bayesian U-Net. CONCLUSIONS: Both AL strategies based on uncertainty quantification from Bayesian U-Net BALD, and ME, provided improved segmentation and lesion detection accuracy for CBCTs. AL may contribute to reducing extensive labeling needs for training AI algorithms for biomedical image analysis in dentistry.