Fractal analysis and PAI evaluation of healing after endodontic treatment and retreatment: A 24-month follow-up

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Materials and methods Eighty-three mandibular teeth with 5 mm lesions from 76 patients were selected, and then the teeth were divided into two groups: the primary endodontic treatment group and the retreatment group. Panoramic X-rays evaluated before and after 2 years of treatment were determined in both treatment groups. Differences between groups were evaluated by fractal analysis. Results Post-treatment fractal dimensions were not statistically significant in both groups compared to pre-treatment(p > 0,05). There was no statistically significant difference between the groups regarding the fractal dimension. Statistically significant decreases were observed in the PAI values within the group(p 0,05). Conclusions There was no difference in success rate between the first root canal treatment and retreatment. Clinical trial number: Not applicable Fractal analysis Region of interest (ROI) Retreatment PAI Root canal treatment Panoramic film Figures Figure 1 Figure 2 Introduction The main objectives of root canal therapy are to ensure the continuity of long-term function and prevent re-infection in teeth with pulpal and periapical diseases caused by caries or trauma [ 1 ]. Retreatment has the same purpose as the primary endodontic treatment of infected root canals. Nonsurgical endodontic retreatment is often preferred due to its conservative nature and ability to preserve the natural tooth structure [ 2 ]​. This is achieved by removing the initial root canal filling material, disinfecting the root canal system, and resealing the root canals [ 3 ]. Apical periodontitis (AP) is a disease characterized by an inflammatory response and bone destruction in the periapical tissues caused by a microbial infection in the dental pulp [ 4 , 5 , 6 ].Periapical lesions resulting from endodontic infections generally range from 5mm to 8 mm in diameter [ 7 , 8 ]. The treatment of large lesions effectively eliminates infection [ 9 ]. As a result of correct treatment, the healing of a periapical lesion occurs with complex tissue repair. The radiolucent area is decreased in follow-up radiographs taken at regular intervals [ 10 , 11 ]. The evaluation of periapical lesion healing in endodontics relies on a combination of clinical, radiographic, and biomolecular methods. Clinically, healing is indicated by the resolution of symptoms, such as the absence of pain on palpation or percussion [ 12 ]​. Radiographic assessment is a fundamental tool in monitoring periapical healing, allowing visualization of lesion size reductions and surrounding bone density increases [ 13 ]​. The Periapical Index (PAI) provides a standardized method for categorizing and tracking the radiographic appearance of lesions over time, offering a reliable measure of healing progression [ 14 ]​. PAI can be classified from one to five according to the appearance of AP on the X-ray[ 15 ]. Advanced imaging techniques, such as fractal analysis, further enhance this evaluation by providing quantitative insights into trabecular bone structure changes during the healing process​ [ 16 ]. The box-counting fractal analysis method is objective in the trabecular bone evaluation and provides quantitative data. In some studies, the follow-up of lesion healing in the relevant region was carried out by recording radiographs taken before and after root canal treatment and evaluating the trabecular bone structure with fractal analysis [ 17 , 18 ]. Many studies have evaluated periapical lesion healing in endodontics, especially using the PAI method [ 19 , 20 ]. Recent investigations have focused on fractal analysis to assess bone healing or changes in bone density in the periapical region following endodontic therapy [ 18 ]. Yet, most of these studies predominantly concentrate on outcomes observed after the initial root canal procedure. In light of this, to the best of our knowledge, this present study is the first to assess the healing of lesions with a diameter of 5 mm and above using fractal analysis after endodontic treatment for the initial and retreatment cases. This study aims to evaluate the improvement of teeth with a large lesion size during the first endodontic treatment and retreatment at the end of 24 months using the box-counting fractal analysis method and the Periapical Index (PAI) method. According to the null hypothesis, the lesion healing is similar after the first treatment and retreatment. Materials and Methods This single-center retrospective study uses recorded panoramic radiographs of patients taken from the Tokat Gaziosmanpaşa University’s Faculty of Dentistry archives. All procedures performed in studies involving human biological material were by the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the ethics committee of Tokat Gaziosmanpaşa University’s Faculty of Medicine, project number 20- KAEK-248. A total of 76 patients were selected from those treated at the Department of Endodontics between March 2013 and February 2020; the inclusion criteria were patients aged 18–63 years, systemically healthy, with lesion diameters of 5 mm and above in the root apex, with 24 months of follow-up X-rays, with no broken instruments in the root, with no perforation, with no internal and external root resorption, and with no incomplete or overfilling. A power calculation was done based on preliminary data to determine the necessary sample size. According to the G-power analysis, an effect size of 0.5 with α = 0.05 would yield a power of 0.80 at this sample size. Eighty-three mandibular teeth with large periapical lesions were divided into the primary endodontic treatment group (n = 42) and the retreatment group (n = 41). Pre-op panoramic X-rays and 24-month follow-up panoramic X-rays were selected from both treatment groups. All panoramic X-rays taken from the patients were captured for 9 s at 70 kVp and 10 mA using Morita Veraviewepocs 2D (Kyoto, Japan). Lesion diameter measurements were made using the ImageJ 1.3 program(ImageJ; US National Institutes of Health, Bethesda, MD). Panoramic X-rays were transferred to the ImageJ 1.3 (ImageJ; US National Institutes of Health, Bethesda, MD) program. In the panoramic X-ray, a reference with a known actual length was measured in ImageJ. These measurements were repeated in the anterior, premolar, and molar regions in the panoramic X-rays, and separate magnification amounts were determined for the three regions. The distance between the two most distant points of the lesion was calculated by providing calibration with the obtained coefficient. Teeth with lesion areas of 5 mm and above were selected and recorded. In multi-rooted teeth, the roots of teeth with larger lesion sizes were included in the study. While determining the lesion sizes; high-resolution panoramic X-rays with the same magnification were usedMandible anterior, premolar, and molar teeth were included in the study. Fractal analysis Fractal analysis was conducted using the method developed by White & Rudolph(White et al., 1999). The process steps are as follows: Panoramic radiography was transferred to the ImageJ program (Fig. 1 ). The regions of interest (ROI) desired to be studied were selected with a size of 60 x 60 square pixels (Fig. 2 a). The selected ROI was cut, saved, and duplicated in JPEG format. The selected ROI areas did not contain anatomical formations such as tooth roots and mandibular canals. A 'Gaussian Blur' sigma 35-pixel filter was applied to blur the areas of high and medium brightness originating from soft tissue and different bone thicknesses (Fig. 2 b). Using the 'Subtract' application, the blurred image was removed from the original image (Fig. 2 c). Using the 'Add' application, 128 gray tones for each pixel were added and an image with an average of 128 was obtained (Fig. 2 d). Using the 'Threshold' option, the image was converted into a two-color black and white image (Fig. 2 e). Thus, the bone marrow and trabecular structures became distinguishable. The noise areas in the image were diminished using the 'Erode' option (Fig. 2 f). The fields found were expanded using the 'Dilate' option (Fig. 2 g). Using the 'Invert' option, the white areas were turned into black and the black areas were turned into white. The outline of the trabecular bone was then revealed (Fig. 2 h). Using the 'Skeletonization' option, the skeletal lines of the trabecular bone were revealed (Fig. 2ı). The negative slope of the linear regression of the curve was calculated by dividing 2, 3, 4, 6, 8, 12, 16, 32, and 64-pixel squares according to the box-counting method of fractal analysis. The slope obtained represents the fractal dimension of the selected area. After calculating the fractal dimensions, the periapical region of the teeth was evaluated according to the PAI classification. PAI 1: Normal apical periodontium PAI 2: There are changes in the bone, but there is not enough bone loss to be observed on the radiography. PAI 3: Structural changes are observed in the bone diagnosed with apical periodontitis. PAI 4: There is bone loss with well-defined borders. PAI 5: Advanced bone loss and large radiolucent areas are observed. Statistical analysis Descriptive analyses were carried out to provide information about the general characteristics of the study groups. The data on quantitative values were given as Mean ± Standard Deviation, while the data on qualitative values were presented as n(%). The differences between the groups regarding quantitative values were examined with the Independent Samples T-Test or the Mann-Whitney U Test, considering parametric properties. The differences between the groups regarding qualitative values were evaluated with the chi-squared test. When p values were calculated less than 0.05, it was considered statistically significant. A ready-made statistical software was used in the calculations (IBM SPSS Statistics 19, SPSS Inc., and IBM Co., Somers, NY). Results The treatment options of the patients included in the study, as well as their dental groups and sex categories, are given in Table 1 . Table 1 Patient demographic data Parameter Subcategories First endodontic treatment retreatment Gender Dental groups Female Male Mandibular anterior Mandibular canine Mandibular premolar Mandibular molar 25 (60,9) 16 (39,1) 4 (9,5) 3 (7,1) 10 (23,8) 25 (59,5) 20 (57,1) 15(42,9) 4 (9,7) 0 (0) 10 (24,3) 27 (65,8) There is no statistically significant difference in both groups in terms of fractal dimensions before treatment compared to their 24-month follow-up x-rays (p > 0.05) (Table 2 ). Table 2 Comparison of the mean fractal values of the first endodontic treatment and retreatment group before and after treatment Treatment P1 First Endodontic treatment (N = 42) retreatment (N = 41) Before treatment 1,48 ± 0,11 1,45 ± 0,16 0,334 After treatment 1,52 ± 0,12 1,50 ± 0,15 0,595 P2 0,101 0,073 There is no statistically significant difference between sexes in inter-group and intragroup comparisons after the first endodontic treatment and retreatment (p > 0.05) (Table 3 ). Table 3 Comparison of fractal dimension difference values between men and women First endodontic treatment retreatment Female (n = 26) Male (n = 16) Female (n = 22) Male (n = 19) Fractal dimension 0,11 ± 0,08 0,15 ± 0,15 0,16 ± 0,10 0,17 ± 0,14 0,114 0,730 p1 0,310 0,770 (p2:For female; p3:For male), p value is considered significant at the 0.05 level. There was no statistically significant difference between time-dependent groups in terms of fractal dimension differences(p > 0.05) (Table 4 ). Table 4 Comparison of fractal dimension difference values in the first endodontic treatment and retreatment group Treatment p First Endodontic treatment (N = 42) retreatment (N = 41) Fractal dimension differences 0,13 ± 0,11 0,16 ± 0,12 0,188 PAI evaluations were not statistically significant in terms of time-dependent decreases in both groups(p > 0.05). Still, in intra-group comparisons, statistically significant reductions were observed in pre- and post-treatment PAI scores in the first endodontic treatment and retreatment groups (p < 0.001) (Table 5 , 6 ). Table 5 Comparison of pre- and post-treatment PAI values in the first endodontic treatment and retreatment group. Pai Score Treatment p First Endodontic Treatment (N = 42) retreatment (N = 41) Before treatment 4 7(41,2) 10(58,8) 0,549 5 35(53,0) 31(47,0) After treatment 1 30(54,5) 25(45,5) 0,559 2 4(40,0) 6(60,0) 3 2(28,6) 5(71,4) 4 2(40,0) 3(60,0) 5 4(66,7) 2(33,3) Table 6 Comparison of pre- and post-treatment PAI values in the first endodontic treatment and retreatment group. Treatment First Endodontic Treatment (n = 42) retreatment (n = 41) Pai (Before treatment) 4,83 ± 0,38 4,76 ± 0,43 Pai (After treatment) 1,71 ± 1,33 1,80 ± 1,21 p < 0,001* <0,001* Discussion The success rates of endodontic treatment for teeth with AP are based on the analysis of clinical signs, findings, and radiographic evaluations [ 21 ]. The teeth and surrounding tissues are healed if there are no clinical and radiographic symptoms and radiolucent areas in the follow-up sessions after endodontic treatment [ 22 ]. Instead of using traditional indices such as PAI, we found it appropriate to evaluate periapical healing using fractal analysis in this study. Fractal analysis is used in endodontic studies to detect periapical healing because it is quantitative, reliable, economical, easy to apply, and not affected by variables such as projection geometry and radiodensity; thus, objective data about trabecular bone patterns are obtained [ 23 ]. This study evaluates extensive periapical lesion healing after the first endodontic treatment and retreatment using fractal analysis after 24 months of follow-up. The PAI scores supported the fractal analysis results. To the best of our knowledge, comparing the first and second root canal treatments of teeth with 5mm lesions has not yet been conducted in the literature using fractal analysis. The null hypothesis of the study that trabecular bone healing is similar after the first endodontic treatment and retreatment was accepted. Studies have shown that a high fractal dimension (FD) value indicates a more complex structure and smaller gaps between the bone trabeculae. In contrast, a low FD value means the bone structure is simple and has more space in the bone trabeculae. The ROI position is an important parameter that affects fractal analysis results [ 24 ]. In a previous study, the FD values of the ROI containing no anatomical structure or dental tissue were compared with the FD values of the ROI containing dental tissue or anatomical structure, and the FD values ​​that contained dental tissue were found to be significantly different from each other. Dental structures should not be included while selecting the ROI [ 25 ]. In light of this information, in this study, a ROI in the exact location and size was generated using pre-op and 24-month follow-up radiographs of the same tooth to eliminate errors related to the location and size of the ROI. Chen et al. [ 17 ]. reported increased FD values measured from the periapical area in intraoral radiographs taken one year after a successful root canal. In contrast, Yu et al [ 26 ]. Observed decreased FD values in reactive bone sites after clinically successful endodontic treatments. According to one study, FD values increased significantly around the root tip after root canal treatment, and a significant decrease was detected in the adjacent region just above the apical lesion in cases that fully healed one year after root canal treatment [ 27 ]. Uğur Aydın et al. reported an increase in FD values after root canal treatment due to a one-year follow-up of the diabetes mellitus(DM) and the control groups compared with the pre-treatment group [ 20 ]. According to the findings of our study, in intra-group comparisons, the FD values before and after a 24-month follow-up in both treatment groups were numerically higher after root canal treatment. However, the differences were not statistically significant. Intergroup comparisons between the groups found no statistically significant difference in the mean FD values of the first endodontic treatment and retreatment. The differences between the two studies may be due to the type of X-ray used, the size of the lesions, and the duration of follow-up. Periapical conditions were also evaluated using the PAI index to determine whether the increase in FD values after root canal treatment was due to a newly formed trabecular pattern or decalcification. There is no correlation between the PAI values and FD in this subject. Thus, although the increase in FD values after root canal treatment was not statistically significant, it could have been caused by the rise in trabeculation due to healing. The PAI measurements, which include many variables, are subjective evaluations, so the measurements may not be accurate. In contrast, measurements in the trabeculation areas are calculated using objective values in fractal analyses. Therefore, there may be inconsistencies between the PAI and fractal analysis results. There is no consensus in the literature that gender is an effective factor in the success of endodontic treatment. Aydın et al. reported that the success of periapical surgery in diabetic patients was not different regardless of sex [ 24 ]. A systematic review found that sex and age did not significantly affect lesion healing in the periapical region after the first and second root canal treatments. Similarly, in the present study, no statistically significant difference was found between males and females in the fractal analysis depending on the treatment options. Conversely, Marquis et al. reported that the success of endodontic treatment was higher in females than in males. Ling et al. showed that the fractal dimensions significantly differed by age and sex [ 28 ]. These different results may be due to the population, age, sample size, or inclusion criteria in these studies. Bollen et al. compared FD values measured on both panoramic and periapical radiographs and found lower in panoramic radiographs [ 29 ]. This study's lower FD on the panoramic radiographs is consistent with previous studies. Trabecular thickness was more expansive due to the lower resolution observed in the panoramic radiographs. This may explain the lack of a significant difference in the fractal analysis in our study. The fractal analysis limits this study, which was performed on panoramic X-rays. This could have prevented some relationships from being statistically significant. Nevertheless, the findings can shed light on future scientific studies. Further studies with larger samples are needed in the future. Conclusion This study found no difference in success between the first root canal treatment and retreatment. Moreover, no correlation was observed between the fractal analysis and the PAI assessment. Nevertheless, changes in FD measurements may be helpful as a clinical technique to determine the success of root canal treatment. It is recommended that further studies be conducted with larger populations using three-dimensional imaging techniques such as cone beam computed tomography (CBCT). Changes in FD values ​​can be used as a supplement in the evaluation of clinical success. Abbreviations AP Apical periodontitis CBCT Cone beam computed tomography DM Diabetes mellitus FD Fractal dimension PAI The periapical index ROI Region of interest Declarations Acknowledgments Not applicable Funding This research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors. No funding declaration in the manuscript. Author information Authors and Affiliations Department of Endodontics, Faculty of Dentistry, Tokat Gaziosmanpasa University, Tokat, Turkey Hilal Ekmen, Huda Melike Bayram Contributions This article is derived from Hilal Ekmen's specialty thesis. Conceptualization and proofreading of the manuscript; Hilal Ekmen, H. Melike Bayram. Literature search, study selection, data extraction, outcome assessment, writing, and managing; H. Melike Bayram, Hilal Ekmen. Corresponding author Correspondence to Huda Melike Bayram Ethics declarations Ethics approval and consent to participate All procedures performed in studies involving human biological material were by the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all participants. This study was approved by the ethics committee of Tokat Gaziosmanpaşa University’s Faculty of Medicine, project number 20- KAEK-248. The informed consent form was obtained. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Data availability The data used and /or analyzed during the current study are available from the corresponding author upon reasonable request. References Peeran SW, Thiruneervannan M, Abdalla KA, Mugrabi MH. Endo-period lesions. IJSTR. 2013;5(2):268–74. Rodríguez G, Patel S, Durán-Sindreu F, Roig M, Abella F. Infuence of cone-beam computed tomography on endodontic retreatment strategies among general dental practitioners and endodontists. J Endod. 2017;43(9):1433–37. Bergenholtz G, Hörsted-Bindslev P, Reit C. Textbook of endodontology. JohnWiley &Sons.United Kingdom: Academic; 2013. Azuma MM, Samuel RO, Gomes-Filho JE, Dezan-Junior E, Cintra L. T.A. The role of IL 6 on apical periodontitis: a systematic review. Int Endod J. 2014;47(7):615–21. Kakehashi S, Stanley H, Fitzgerald R. The effects of surgical exposures of dental pulps in germ-free and conventional laboratory rats. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1965; 20(3): 340–49. Möller ÅJ, Fabricius L, Dahlen G, Ohman AE, Heyden GUY. Influence on periapical tissues of indigenous oral bacteria and necrotic pulp tissue in monkeys. Eur J Oral Sci. 1981;89(6):475–84. Murphy WK, Kaugars GE, Collett WK, Dodds RN. Healing of periapical radiolucencies after nonsurgical endodontic therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1991;71(5):620–24. Sjögren U, Figdor D, Persson S, Sundqvist G. Influence of infection at the time of root filling on the outcome of endodontic treatment of teeth with apical periodontitis. Int Endod J. 1997;30(5):297–306. Nair P. On the causes of persistent apical periodontitis: a review. Int Endod J. 2006;39(4):249–81. Grahnen H. The prognosis of pulp and root canal therapy A clinical and radiographic follow-up examination. Odontol Revy. 1961;12(1):146–65. Kerekes K, Tronstad LL. Long-term results of endodontic treatment performed with a standardized technique. J Endod. 1979;5(3):83–90. Chugal N, Mallya SM, Kahler B, Lin LM. Endodontic treatment outcomes. Dent Clin North Am. 2017;61:59–80. Nedderman TA, Hartwell GR, Protell FR. A comparison of root surfaces following apical root resection with various burs: scanning electron microscopic evaluation. J Endod. 1988;14(9):423–27. Marotta PS, Fontes TV, Armada L, Lima KC, Rocas IN, Siqueira JF. Type 2 diabetes mellitus and the prevalence of apical periodontitis and endodontic treatment in an adult Brazilian population. J Endod. 2012;38:297–300. Ørstavik D, Kerekes K, Eriksen HM. The periapical index: a scoring system for radiographic assessment of apical periodontitis. Dent Trauma. 1986;2(1):20–34. White SC, Rudolph DJ. Alterations of the trabecular pattern of the jaws in patients with osteoporosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1994;88:628–35. Chen S-K, Oviir T, Lin CH, Leu LJ, Cho BH, Hollender L. Digital imaging analysis with mathematical morphology and fractal dimension for evaluation of periapical lesions following endodontic treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100(4):467–72. Tosun S, Karataslioglu E, Tulgar MM, Derindag G. Retrospective fractal analysis of one- year follow-up data obtained after single-visit nonsurgical endodontic retreatment on periapical radiographs. Clin Oral Investig. 2021;25(11):6465–72. Olcay K, Eyüboglu TF, Özcan MM. Clinical outcomes of non-surgical multiple visit root canal retreatment: a retrospective cohort study. Odontol. 2019;10(4):536–45. Uğur Aydın Z, Ocak MG, Bayrak S, Göller Bulut D, Orhan K. The effect of type 2 diabetes mellitus on changes in the fractal dimension of periapical lesion in teeth after root canal treatment: a fractal analysis study. Int Endod J. 2021;54(2):181–89. Jolley L, Majumdar S, Kapila S. Technical factors in fractal analysis of periapical radiographs. Dent Radiolog. 2006;35(6):393–97. Murphy TH, Worley PF, Baraban JM. L-type voltage-sensitive calcium channel mediate synaptic activation of immediate early genes. Neuron. 1991;7(4):625–35. Friedman S. Considerations and concepts of case selection in the management of post- treatment endodontic disease (treatment failure). Endod Top. 2002;1(1):54–78. Aydın ZU, Toptaş O, Bulut DG, Akay N, Kara T, Akbulut N. Effects of root-end filling on the fractal dimension of the periapical bone after periapical surgery: retrospective study. Clin Oral Investig. 2019;23(9):3645–51. Shrout MK, Potter BJ, Hildebolt CF. The effect of image variations on fractal dimension calculations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997;84(1):96–100. Yu YY, Chen H, Lin CH, Chen CM, Oviir T, Chen SK, Hollender L. Fractal dimension analysis of periapical reactive bone in response to root canal treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;107(2):283–88. Huang CC, Chen JC, Chang YC, Jeng JH, Chen CM.. A fractal dimensional approach to successful evaluation of apical healing. Int Endod J. 2013;46(6):523–29. Ling H, Yang X, Li P, Megalooikonomou V, Xu Y, Yang J. Cross gender–age trabecular texture analysis in cone beam CT. Dent Radiol. 2014;43(4):20130324. Bollen AM, Taguchi A, Hujoel PP, Hollender. L.G. Fractal dimension on dental. radiographs. Dent Radiolog. 2001; 30(5): 270–75. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6556414","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":476248545,"identity":"07402e3d-75f4-408e-8e6f-db5725267990","order_by":0,"name":"Hilal Ekmen","email":"","orcid":"","institution":"Tokat Gaziosmanpasa University","correspondingAuthor":false,"prefix":"","firstName":"Hilal","middleName":"","lastName":"Ekmen","suffix":""},{"id":476248546,"identity":"ccfe2149-78c1-4d88-8431-f55b71e89bc1","order_by":1,"name":"Hüda Melike Bayram","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIiWNgGAWjYFAC5oaDDQwMMkAW4wMGhgPEaGEEa+EBaTYgWgsjVAubBFFadNsbGw/OqLDj4W8//Kyap+aOHAP74aMb8GkxO3Ow4eCGM8k8EmfSzG7zHHtmzMCTlnYDr5YbiQ0HH7Yx8zDcYABqYTuc2CDBY4Zfy/2HQC3/6nnkb7B/K+b5R4yWG8AQ29hwmMfgBo8ZM28bMVrOAB0249hxHsMzOcWSc/sOG7MR9Mvxw4c/9tRUy8kdP77xw5tvh+X42Q8fw6sFBTCBY4do5SDA+IMk5aNgFIyCUTBSAADUg1SPngheHwAAAABJRU5ErkJggg==","orcid":"","institution":"Tokat Gaziosmanpasa University","correspondingAuthor":true,"prefix":"","firstName":"Hüda","middleName":"Melike","lastName":"Bayram","suffix":""}],"badges":[],"createdAt":"2025-04-29 12:23:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6556414/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6556414/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85737035,"identity":"4438a996-a1a7-4480-938d-0d968a8f6254","added_by":"auto","created_at":"2025-07-01 08:09:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1462216,"visible":true,"origin":"","legend":"\u003cp\u003eDetermination of the ROI in a panoramic radiograph\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6556414/v1/4064c1a59b2ccfc72554b2e4.png"},{"id":85737029,"identity":"ceffa397-68d8-4f89-b6ef-ccfa3335ea6b","added_by":"auto","created_at":"2025-07-01 08:09:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":48341,"visible":true,"origin":"","legend":"\u003cp\u003eFractal analysis stages in bone\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6556414/v1/ab37966cd5b5593cabc4ebcb.png"},{"id":86997743,"identity":"10d16849-fa5e-4c43-b3c8-35c39517e071","added_by":"auto","created_at":"2025-07-18 06:16:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1277192,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6556414/v1/52c48edf-0559-4d17-b4ba-a0246831041c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Fractal analysis and PAI evaluation of healing after endodontic treatment and retreatment: A 24-month follow-up","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe main objectives of root canal therapy are to ensure the continuity of long-term function and prevent re-infection in teeth with pulpal and periapical diseases caused by caries or trauma [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Retreatment has the same purpose as the primary endodontic treatment of infected root canals. Nonsurgical endodontic retreatment is often preferred due to its conservative nature and ability to preserve the natural tooth structure [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]​. This is achieved by removing the initial root canal filling material, disinfecting the root canal system, and resealing the root canals [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eApical periodontitis (AP) is a disease characterized by an inflammatory response and bone destruction in the periapical tissues caused by a microbial infection in the dental pulp [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].Periapical lesions resulting from endodontic infections generally range from 5mm to 8 mm in diameter [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The treatment of large lesions effectively eliminates infection [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. As a result of correct treatment, the healing of a periapical lesion occurs with complex tissue repair. The radiolucent area is decreased in follow-up radiographs taken at regular intervals [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The evaluation of periapical lesion healing in endodontics relies on a combination of clinical, radiographic, and biomolecular methods. Clinically, healing is indicated by the resolution of symptoms, such as the absence of pain on palpation or percussion [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]​. Radiographic assessment is a fundamental tool in monitoring periapical healing, allowing visualization of lesion size reductions and surrounding bone density increases [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]​.\u003c/p\u003e \u003cp\u003eThe Periapical Index (PAI) provides a standardized method for categorizing and tracking the radiographic appearance of lesions over time, offering a reliable measure of healing progression [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]​. PAI can be classified from one to five according to the appearance of AP on the X-ray[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Advanced imaging techniques, such as fractal analysis, further enhance this evaluation by providing quantitative insights into trabecular bone structure changes during the healing process​ [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe box-counting fractal analysis method is objective in the trabecular bone evaluation and provides quantitative data. In some studies, the follow-up of lesion healing in the relevant region was carried out by recording radiographs taken before and after root canal treatment and evaluating the trabecular bone structure with fractal analysis [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Many studies have evaluated periapical lesion healing in endodontics, especially using the PAI method [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Recent investigations have focused on fractal analysis to assess bone healing or changes in bone density in the periapical region following endodontic therapy [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eYet, most of these studies predominantly concentrate on outcomes observed after the initial root canal procedure. In light of this, to the best of our knowledge, this present study is the first to assess the healing of lesions with a diameter of 5 mm and above using fractal analysis after endodontic treatment for the initial and retreatment cases. This study aims to evaluate the improvement of teeth with a large lesion size during the first endodontic treatment and retreatment at the end of 24 months using the box-counting fractal analysis method and the Periapical Index (PAI) method. According to the null hypothesis, the lesion healing is similar after the first treatment and retreatment.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis single-center retrospective study uses recorded panoramic radiographs of patients taken from the Tokat Gaziosmanpaşa University\u0026rsquo;s Faculty of Dentistry archives. All procedures performed in studies involving human biological material were by the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the ethics committee of Tokat Gaziosmanpaşa University\u0026rsquo;s Faculty of Medicine, project number 20- KAEK-248. A total of 76 patients were selected from those treated at the Department of Endodontics between March 2013 and February 2020; the inclusion criteria were patients aged 18\u0026ndash;63 years, systemically healthy, with lesion diameters of 5 mm and above in the root apex, with 24 months of follow-up X-rays, with no broken instruments in the root, with no perforation, with no internal and external root resorption, and with no incomplete or overfilling.\u003c/p\u003e \u003cp\u003eA power calculation was done based on preliminary data to determine the necessary sample size. According to the G-power analysis, an effect size of 0.5 with α\u0026thinsp;=\u0026thinsp;0.05 would yield a power of 0.80 at this sample size. Eighty-three mandibular teeth with large periapical lesions were divided into the primary endodontic treatment group (n\u0026thinsp;=\u0026thinsp;42) and the retreatment group (n\u0026thinsp;=\u0026thinsp;41). Pre-op panoramic X-rays and 24-month follow-up panoramic X-rays were selected from both treatment groups. All panoramic X-rays taken from the patients were captured for 9 s at 70 kVp and 10 mA using Morita Veraviewepocs 2D (Kyoto, Japan). Lesion diameter measurements were made using the ImageJ 1.3 program(ImageJ; US National Institutes of Health, Bethesda, MD). Panoramic X-rays were transferred to the ImageJ 1.3 (ImageJ; US National Institutes of Health, Bethesda, MD) program. In the panoramic X-ray, a reference with a known actual length was measured in ImageJ. These measurements were repeated in the anterior, premolar, and molar regions in the panoramic X-rays, and separate magnification amounts were determined for the three regions. The distance between the two most distant points of the lesion was calculated by providing calibration with the obtained coefficient. Teeth with lesion areas of 5 mm and above were selected and recorded. In multi-rooted teeth, the roots of teeth with larger lesion sizes were included in the study. While determining the lesion sizes; high-resolution panoramic X-rays with the same magnification were usedMandible anterior, premolar, and molar teeth were included in the study.\u003c/p\u003e \u003cp\u003eFractal analysis\u003c/p\u003e \u003cp\u003eFractal analysis was conducted using the method developed by White \u0026amp; Rudolph(White et al., 1999). The process steps are as follows:\u003c/p\u003e \u003cp\u003ePanoramic radiography was transferred to the ImageJ program (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe regions of interest (ROI) desired to be studied were selected with a size of 60 x 60 square pixels (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). The selected ROI was cut, saved, and duplicated in JPEG format. The selected ROI areas did not contain anatomical formations such as tooth roots and mandibular canals. A 'Gaussian Blur' sigma 35-pixel filter was applied to blur the areas of high and medium brightness originating from soft tissue and different bone thicknesses (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). Using the 'Subtract' application, the blurred image was removed from the original image (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec). Using the 'Add' application, 128 gray tones for each pixel were added and an image with an average of 128 was obtained (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed). Using the 'Threshold' option, the image was converted into a two-color black and white image (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ee). Thus, the bone marrow and trabecular structures became distinguishable. The noise areas in the image were diminished using the 'Erode' option (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ef). The fields found were expanded using the 'Dilate' option (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eg). Using the 'Invert' option, the white areas were turned into black and the black areas were turned into white. The outline of the trabecular bone was then revealed (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eh). Using the 'Skeletonization' option, the skeletal lines of the trabecular bone were revealed (Fig.\u0026nbsp;2ı). The negative slope of the linear regression of the curve was calculated by dividing 2, 3, 4, 6, 8, 12, 16, 32, and 64-pixel squares according to the box-counting method of fractal analysis. The slope obtained represents the fractal dimension of the selected area. After calculating the fractal dimensions, the periapical region of the teeth was evaluated according to the PAI classification.\u003c/p\u003e \u003cp\u003ePAI 1: Normal apical periodontium\u003c/p\u003e \u003cp\u003ePAI 2: There are changes in the bone, but there is not enough bone loss to be observed on the radiography.\u003c/p\u003e \u003cp\u003ePAI 3: Structural changes are observed in the bone diagnosed with apical periodontitis.\u003c/p\u003e \u003cp\u003ePAI 4: There is bone loss with well-defined borders.\u003c/p\u003e \u003cp\u003ePAI 5: Advanced bone loss and large radiolucent areas are observed.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eDescriptive analyses were carried out to provide information about the general characteristics of the study groups. The data on quantitative values were given as Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;Standard Deviation, while the data on qualitative values were presented as n(%). The differences between the groups regarding quantitative values were examined with the Independent Samples T-Test or the Mann-Whitney U Test, considering parametric properties. The differences between the groups regarding qualitative values were evaluated with the chi-squared test. When p values were calculated less than 0.05, it was considered statistically significant. A ready-made statistical software was used in the calculations (IBM SPSS Statistics 19, SPSS Inc., and IBM Co., Somers, NY).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe treatment options of the patients included in the study, as well as their dental groups and sex categories, are given in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient demographic data\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSubcategories\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFirst endodontic treatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eretreatment\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eDental groups\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003cp\u003eMale\u003c/p\u003e \u003cp\u003eMandibular anterior\u003c/p\u003e \u003cp\u003eMandibular canine\u003c/p\u003e \u003cp\u003eMandibular premolar\u003c/p\u003e \u003cp\u003eMandibular molar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (60,9)\u003c/p\u003e \u003cp\u003e16 (39,1)\u003c/p\u003e \u003cp\u003e4 (9,5)\u003c/p\u003e \u003cp\u003e3 (7,1)\u003c/p\u003e \u003cp\u003e10 (23,8)\u003c/p\u003e \u003cp\u003e25 (59,5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (57,1)\u003c/p\u003e \u003cp\u003e15(42,9)\u003c/p\u003e \u003cp\u003e4 (9,7)\u003c/p\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003cp\u003e10 (24,3)\u003c/p\u003e \u003cp\u003e27 (65,8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThere is no statistically significant difference in both groups in terms of fractal dimensions before treatment compared to their 24-month follow-up x-rays (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of the mean fractal values of the first endodontic treatment and retreatment group before and after treatment\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP1\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFirst Endodontic treatment\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;42)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eretreatment\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;41)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBefore treatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,48\u0026thinsp;\u0026plusmn;\u0026thinsp;0,11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,45\u0026thinsp;\u0026plusmn;\u0026thinsp;0,16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0,334\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAfter treatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,52\u0026thinsp;\u0026plusmn;\u0026thinsp;0,12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,50\u0026thinsp;\u0026plusmn;\u0026thinsp;0,15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0,595\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0,073\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThere is no statistically significant difference between sexes in inter-group and intragroup comparisons after the first endodontic treatment and retreatment (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of fractal dimension difference values between men and women\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eFirst endodontic treatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eretreatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFractal dimension\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,11\u0026thinsp;\u0026plusmn;\u0026thinsp;0,08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0,15\u0026thinsp;\u0026plusmn;\u0026thinsp;0,15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0,16\u0026thinsp;\u0026plusmn;\u0026thinsp;0,10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,17\u0026thinsp;\u0026plusmn;\u0026thinsp;0,14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,114\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0,730\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ep1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0,310\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0,770\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e(p2:For female; p3:For male), p value is considered significant at the 0.05 level.\u003c/p\u003e \u003cp\u003eThere was no statistically significant difference between time-dependent groups in terms of fractal dimension differences(p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of fractal dimension difference values in the first endodontic treatment and retreatment group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eFirst Endodontic treatment\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;42)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eretreatment\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;41)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFractal dimension differences\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,13\u0026thinsp;\u0026plusmn;\u0026thinsp;0,11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0,16\u0026thinsp;\u0026plusmn;\u0026thinsp;0,12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,188\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePAI evaluations were not statistically significant in terms of time-dependent decreases in both groups(p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Still, in intra-group comparisons, statistically significant reductions were observed in pre- and post-treatment PAI scores in the first endodontic treatment and retreatment groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, \u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of pre- and post-treatment PAI values in the first endodontic treatment and retreatment group.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003ePai Score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFirst Endodontic Treatment\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eretreatment\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;41)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eBefore treatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(41,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10(58,8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0,549\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35(53,0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31(47,0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e\u003cb\u003eAfter treatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30(54,5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25(45,5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"4\" rowspan=\"5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0,559\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(40,0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6(60,0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(28,6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(71,4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(40,0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(60,0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(66,7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(33,3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of pre- and post-treatment PAI values in the first endodontic treatment and retreatment group.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFirst Endodontic Treatment\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;42)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eretreatment\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;41)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePai (Before treatment)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,83\u0026thinsp;\u0026plusmn;\u0026thinsp;0,38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4,76\u0026thinsp;\u0026plusmn;\u0026thinsp;0,43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePai (After treatment)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,71\u0026thinsp;\u0026plusmn;\u0026thinsp;1,33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,80\u0026thinsp;\u0026plusmn;\u0026thinsp;1,21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ep\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0,001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;0,001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe success rates of endodontic treatment for teeth with AP are based on the analysis of clinical signs, findings, and radiographic evaluations [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The teeth and surrounding tissues are healed if there are no clinical and radiographic symptoms and radiolucent areas in the follow-up sessions after endodontic treatment [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Instead of using traditional indices such as PAI, we found it appropriate to evaluate periapical healing using fractal analysis in this study. Fractal analysis is used in endodontic studies to detect periapical healing because it is quantitative, reliable, economical, easy to apply, and not affected by variables such as projection geometry and radiodensity; thus, objective data about trabecular bone patterns are obtained [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. This study evaluates extensive periapical lesion healing after the first endodontic treatment and retreatment using fractal analysis after 24 months of follow-up. The PAI scores supported the fractal analysis results. To the best of our knowledge, comparing the first and second root canal treatments of teeth with 5mm lesions has not yet been conducted in the literature using fractal analysis. The null hypothesis of the study that trabecular bone healing is similar after the first endodontic treatment and retreatment was accepted.\u003c/p\u003e \u003cp\u003eStudies have shown that a high fractal dimension (FD) value indicates a more complex structure and smaller gaps between the bone trabeculae. In contrast, a low FD value means the bone structure is simple and has more space in the bone trabeculae. The ROI position is an important parameter that affects fractal analysis results [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. In a previous study, the FD values of the ROI containing no anatomical structure or dental tissue were compared with the FD values of the ROI containing dental tissue or anatomical structure, and the FD values ​​that contained dental tissue were found to be significantly different from each other. Dental structures should not be included while selecting the ROI [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In light of this information, in this study, a ROI in the exact location and size was generated using pre-op and 24-month follow-up radiographs of the same tooth to eliminate errors related to the location and size of the ROI.\u003c/p\u003e \u003cp\u003eChen et al. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. reported increased FD values measured from the periapical area in intraoral radiographs taken one year after a successful root canal. In contrast, Yu et al [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Observed decreased FD values in reactive bone sites after clinically successful endodontic treatments. According to one study, FD values increased significantly around the root tip after root canal treatment, and a significant decrease was detected in the adjacent region just above the apical lesion in cases that fully healed one year after root canal treatment [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Uğur Aydın et al. reported an increase in FD values after root canal treatment due to a one-year follow-up of the diabetes mellitus(DM) and the control groups compared with the pre-treatment group [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. According to the findings of our study, in intra-group comparisons, the FD values before and after a 24-month follow-up in both treatment groups were numerically higher after root canal treatment. However, the differences were not statistically significant. Intergroup comparisons between the groups found no statistically significant difference in the mean FD values of the first endodontic treatment and retreatment. The differences between the two studies may be due to the type of X-ray used, the size of the lesions, and the duration of follow-up.\u003c/p\u003e \u003cp\u003ePeriapical conditions were also evaluated using the PAI index to determine whether the increase in FD values after root canal treatment was due to a newly formed trabecular pattern or decalcification. There is no correlation between the PAI values and FD in this subject. Thus, although the increase in FD values after root canal treatment was not statistically significant, it could have been caused by the rise in trabeculation due to healing. The PAI measurements, which include many variables, are subjective evaluations, so the measurements may not be accurate. In contrast, measurements in the trabeculation areas are calculated using objective values in fractal analyses. Therefore, there may be inconsistencies between the PAI and fractal analysis results. There is no consensus in the literature that gender is an effective factor in the success of endodontic treatment. Aydın et al. reported that the success of periapical surgery in diabetic patients was not different regardless of sex [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. A systematic review found that sex and age did not significantly affect lesion healing in the periapical region after the first and second root canal treatments. Similarly, in the present study, no statistically significant difference was found between males and females in the fractal analysis depending on the treatment options. Conversely, Marquis et al. reported that the success of endodontic treatment was higher in females than in males. Ling et al. showed that the fractal dimensions significantly differed by age and sex [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. These different results may be due to the population, age, sample size, or inclusion criteria in these studies. Bollen et al. compared FD values measured on both panoramic and periapical radiographs and found lower in panoramic radiographs [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. This study's lower FD on the panoramic radiographs is consistent with previous studies. Trabecular thickness was more expansive due to the lower resolution observed in the panoramic radiographs. This may explain the lack of a significant difference in the fractal analysis in our study. The fractal analysis limits this study, which was performed on panoramic X-rays. This could have prevented some relationships from being statistically significant. Nevertheless, the findings can shed light on future scientific studies. Further studies with larger samples are needed in the future.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study found no difference in success between the first root canal treatment and retreatment. Moreover, no correlation was observed between the fractal analysis and the PAI assessment. Nevertheless, changes in FD measurements may be helpful as a clinical technique to determine the success of root canal treatment. It is recommended that further studies be conducted with larger populations using three-dimensional imaging techniques such as cone beam computed tomography (CBCT). Changes in FD values ​​can be used as a supplement in the evaluation of clinical success.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eAP\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eApical periodontitis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eCBCT\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCone beam computed tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eDM\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eFD\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFractal dimension\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003ePAI\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eThe periapical index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eROI\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRegion of interest\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors. No funding declaration in the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthors and Affiliations\u003c/p\u003e\n\u003cp\u003eDepartment of Endodontics, Faculty of Dentistry, Tokat Gaziosmanpasa University, Tokat, Turkey\u003c/p\u003e\n\u003cp\u003eHilal Ekmen, Huda Melike Bayram\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis article is derived from Hilal Ekmen\u0026apos;s specialty thesis.\u0026nbsp;Conceptualization and proofreading of the manuscript; Hilal Ekmen, H. Melike Bayram. Literature search, study selection, data extraction, outcome assessment, writing, and managing; H. Melike Bayram, Hilal Ekmen.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCorresponding author\u003c/p\u003e\n\u003cp\u003eCorrespondence to Huda Melike Bayram\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in studies involving human biological material were by the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. \u0026nbsp;Informed consent was obtained from all participants. This study was approved by the ethics committee of Tokat Gaziosmanpaşa University\u0026rsquo;s Faculty of Medicine, project number 20- KAEK-248. The informed consent form was obtained.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data used and /or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePeeran SW, Thiruneervannan M, Abdalla KA, Mugrabi MH. Endo-period lesions. IJSTR. 2013;5(2):268\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRodr\u0026iacute;guez G, Patel S, Dur\u0026aacute;n-Sindreu F, Roig M, Abella F. Infuence of cone-beam computed tomography on endodontic retreatment strategies among general dental practitioners and endodontists. J Endod. 2017;43(9):1433\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBergenholtz G, H\u0026ouml;rsted-Bindslev P, Reit C. Textbook of endodontology. JohnWiley \u0026amp;Sons.United Kingdom: Academic; 2013.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAzuma MM, Samuel RO, Gomes-Filho JE, Dezan-Junior E, Cintra L. T.A. The role of IL 6 on apical periodontitis: a systematic review. Int Endod J. 2014;47(7):615\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKakehashi S, Stanley H, Fitzgerald R. The effects of surgical exposures of dental pulps in germ-free and conventional laboratory rats. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1965; 20(3): 340\u0026ndash;49.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eM\u0026ouml;ller \u0026Aring;J, Fabricius L, Dahlen G, Ohman AE, Heyden GUY. Influence on periapical tissues of indigenous oral bacteria and necrotic pulp tissue in monkeys. Eur J Oral Sci. 1981;89(6):475\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMurphy WK, Kaugars GE, Collett WK, Dodds RN. Healing of periapical radiolucencies after nonsurgical endodontic therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1991;71(5):620\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSj\u0026ouml;gren U, Figdor D, Persson S, Sundqvist G. Influence of infection at the time of root filling on the outcome of endodontic treatment of teeth with apical periodontitis. Int Endod J. 1997;30(5):297\u0026ndash;306.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNair P. On the causes of persistent apical periodontitis: a review. Int Endod J. 2006;39(4):249\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrahnen H. The prognosis of pulp and root canal therapy A clinical and radiographic follow-up examination. Odontol Revy. 1961;12(1):146\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKerekes K, Tronstad LL. Long-term results of endodontic treatment performed with a standardized technique. J Endod. 1979;5(3):83\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChugal N, Mallya SM, Kahler B, Lin LM. Endodontic treatment outcomes. Dent Clin North Am. 2017;61:59\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNedderman TA, Hartwell GR, Protell FR. A comparison of root surfaces following apical root resection with various burs: scanning electron microscopic evaluation. J Endod. 1988;14(9):423\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarotta PS, Fontes TV, Armada L, Lima KC, Rocas IN, Siqueira JF. Type 2 diabetes mellitus and the prevalence of apical periodontitis and endodontic treatment in an adult Brazilian population. J Endod. 2012;38:297\u0026ndash;300.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026Oslash;rstavik D, Kerekes K, Eriksen HM. The periapical index: a scoring system for radiographic assessment of apical periodontitis. Dent Trauma. 1986;2(1):20\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWhite SC, Rudolph DJ. Alterations of the trabecular pattern of the jaws in patients with osteoporosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1994;88:628\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen S-K, Oviir T, Lin CH, Leu LJ, Cho BH, Hollender L. Digital imaging analysis with mathematical morphology and fractal dimension for evaluation of periapical lesions following endodontic treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100(4):467\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTosun S, Karataslioglu E, Tulgar MM, Derindag G. Retrospective fractal analysis of one- year follow-up data obtained after single-visit nonsurgical endodontic retreatment on periapical radiographs. Clin Oral Investig. 2021;25(11):6465\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOlcay K, Ey\u0026uuml;boglu TF, \u0026Ouml;zcan MM. Clinical outcomes of non-surgical multiple visit root canal retreatment: a retrospective cohort study. Odontol. 2019;10(4):536\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUğur Aydın Z, Ocak MG, Bayrak S, G\u0026ouml;ller Bulut D, Orhan K. The effect of type 2 diabetes mellitus on changes in the fractal dimension of periapical lesion in teeth after root canal treatment: a fractal analysis study. Int Endod J. 2021;54(2):181\u0026ndash;89.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJolley L, Majumdar S, Kapila S. Technical factors in fractal analysis of periapical radiographs. Dent Radiolog. 2006;35(6):393\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMurphy TH, Worley PF, Baraban JM. L-type voltage-sensitive calcium channel mediate synaptic activation of immediate early genes. Neuron. 1991;7(4):625\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFriedman S. Considerations and concepts of case selection in the management of post- treatment endodontic disease (treatment failure). Endod Top. 2002;1(1):54\u0026ndash;78.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAydın ZU, Toptaş O, Bulut DG, Akay N, Kara T, Akbulut N. Effects of root-end filling on the fractal dimension of the periapical bone after periapical surgery: retrospective study. Clin Oral Investig. 2019;23(9):3645\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShrout MK, Potter BJ, Hildebolt CF. The effect of image variations on fractal dimension calculations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997;84(1):96\u0026ndash;100.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYu YY, Chen H, Lin CH, Chen CM, Oviir T, Chen SK, Hollender L. Fractal dimension analysis of periapical reactive bone in response to root canal treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;107(2):283\u0026ndash;88.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang CC, Chen JC, Chang YC, Jeng JH, Chen CM.. A fractal dimensional approach to successful evaluation of apical healing. Int Endod J. 2013;46(6):523\u0026ndash;29.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLing H, Yang X, Li P, Megalooikonomou V, Xu Y, Yang J. Cross gender\u0026ndash;age trabecular texture analysis in cone beam CT. Dent Radiol. 2014;43(4):20130324.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBollen AM, Taguchi A, Hujoel PP, Hollender. L.G. Fractal dimension on dental.\u003c/span\u003e \u003cspan\u003eradiographs. Dent Radiolog. 2001; 30(5): 270\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Fractal analysis, Region of interest (ROI), Retreatment, PAI, Root canal treatment, Panoramic film","lastPublishedDoi":"10.21203/rs.3.rs-6556414/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6556414/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study compares the healing after 24 months between initial endodontic treatment and retreatment using fractal analysis and the periapical index (PAI) scores.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEighty-three mandibular teeth with 5 mm lesions from 76 patients were selected, and then the teeth were divided into two groups: the primary endodontic treatment group and the retreatment group. Panoramic X-rays evaluated before and after 2 years of treatment were determined in both treatment groups. Differences between groups were evaluated by fractal analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePost-treatment fractal dimensions were not statistically significant in both groups compared to pre-treatment(p \u0026gt; 0,05). There was no statistically significant difference between the groups regarding the fractal dimension. Statistically significant decreases were observed in the PAI values within the group(p \u0026lt; 0,001), and no significant difference was observed in terms of time-dependent decreases between the groups(p \u0026gt; 0,05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere was no difference in success rate between the first root canal treatment and retreatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eClinical trial number: Not applicable\u003c/p\u003e","manuscriptTitle":"Fractal analysis and PAI evaluation of healing after endodontic treatment and retreatment: A 24-month follow-up","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-01 08:09:01","doi":"10.21203/rs.3.rs-6556414/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d7af54fc-2a38-40a4-9e42-98e8fae7deb5","owner":[],"postedDate":"July 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-18T06:08:48+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-01 08:09:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6556414","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6556414","identity":"rs-6556414","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}