Dentistry, Faculty of
DSpace
UBCV
Arjunan, Sharmila
Master of Science - MSc
University of British Columbia
Objectives: To evaluate the diagnostic accuracy of near infra-red imaging (NIRI) technology of iTero Element 5D intra-oral scanners (index test) by comparing it to bitewing radiography (clinical reference standard) for detecting proximal surface enamel caries (target condition). Methods: We conducted a diagnostic study on 42 consecutive patients (22 males & 20 females) who presented for orthodontic treatment at the University of British Columbia (UBC). Consenting individuals ≥12 years of age received intra-oral digital scanning using iTero Element 5D scanners and full-mouth bitewing radiographs (BWRs). Two experienced pediatric dentists independently evaluated the non-restored proximal surfaces on BWRs and NIRI images for the presence/absence of initial enamel caries. Results: The prevalence of the target condition in the sample population was 5.8%. Of 1110 proximal surfaces included in the analysis, the diagnosis of the target condition was confirmed in 65 surfaces based on BWRs. The index test showed a sensitivity of 60.0%, specificity of 97.7%, positive predictive value of 61.9%, and negative predictive value of 97.5%. The inter- and intra-examiner reliability for BWRs and NIRI images were 0.78, 0.97, 0.85, and 1.0 respectively. The Area Under the Curve (AUC) value for the index test was 0.78 which can be considered acceptable in terms of the test’s ability to distinguish between positive (caries) and negative cases (no caries). Conclusions: The index test showed high specificity and negative predictive value; therefore, it has potential as a non-ionizing screening tool for the detection of proximal surfaces without enamel caries in permanent teeth, particularly in adolescents with a moderate/high caries risk. Acknowledgements: This project was supported by a 2021 Align Research Award (AWD-020121).
ACCURACY OF DIAGNOSING PROXIMAL CARIES USING INTRA-ORAL BITEWING RADIOGRAPHS AND NEAR INFRA-RED IMAGING (NIRI) TECHNOLOGY IN iTERO ELEMENT 5D SCANNERS - AN IN VIVO STUDY by Sharmila Arjunan B.D.S., Rajiv Gandhi University of Health Sciences, 2008 M.D.S. (Orthodontics), Rajiv Gandhi University of Health Sciences, 2013 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Craniofacial Science) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) April 2023 © Sharmila Arjunan, 2023 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, a thesis entitled: Accuracy of Diagnosing Proximal Caries Using Intra-Oral Bitewing Radiographs and Near Infra-Red Imaging (NIRI) Technology In iTero Element 5D Scanners - An In Vivo Study submitted by Sharmila Arjunan in partial fulfillment of the requirements for the degree of Master of Science In Craniofacial Science Examining Committee: Dr. Edwin H.K Yen, Professor, Faculty of Dentistry, UBC Supervisor Dr. Sandra Khong Tai, Clinical Assistant Professor, Faculty of Dentistry, UBC Supervisory Committee Member Dr. Jolanta Aleksejuniene, Associate Professor, Faculty of Dentistry, UBC Supervisory Committee Member Dr. Kavita Mathu-Muju, Associate Professor, Faculty of Dentistry, UBC Supervisory Committee Member iii Abstract Objectives: To evaluate the diagnostic accuracy of near infra-red imaging (NIRI) technology of iTero Element 5D intra-oral scanners (index test) by comparing it to bitewing radiography (clinical reference standard) for detecting proximal surface enamel caries (target condition). Methods: We conducted a diagnostic study on 42 consecutive patients (22 males & 20 females) who presented for orthodontic treatment at the University of British Columbia (UBC). Consenting individuals ≥12 years of age received intra-oral digital scanning using iTero Element 5D scanners and full-mouth bitewing radiographs (BWRs). Two experienced pediatric dentists independently evaluated the non-restored proximal surfaces on BWRs and NIRI images for the presence/absence of initial enamel caries. Results: The prevalence of the target condition in the sample population was 5.8%. Of 1110 proximal surfaces included in the analysis, the diagnosis of the target condition was confirmed in 65 surfaces based on BWRs. The index test showed a sensitivity of 60.0%, specificity of 97.7%, positive predictive value of 61.9%, and negative predictive value of 97.5%. The inter- and intra-examiner reliability for BWRs and NIRI images were 0.78, 0.97, 0.85, and 1.0 respectively. The Area Under the Curve (AUC) value for the index test was 0.78 which can be considered acceptable in terms of the test’s ability to distinguish between positive (caries) and negative cases (no caries). Conclusions: The index test showed high specificity and negative predictive value; therefore, it has potential as a non-ionizing screening tool for the detection of proximal surfaces without enamel caries in permanent teeth, particularly in adolescents with a moderate/high caries risk. Acknowledgements: This project was supported by a 2021 Align Research Award (AWD-020121). iv Lay Summary Radiographic methods to diagnose caries uses ionizing radiation limiting its ability to be used frequently, especially in growing children and pregnant women. Therefore, there is a constant need to test the diagnostic accuracy of non-ionizing methods to detect early enamel caries in proximal surfaces. This prospective clinical study compares the ability of near infra-red imaging (NIRI) technology of iTero element 5D scanners and intraoral bitewing radiographs (BWRs) in detecting proximal surface enamel caries in patients starting orthodontic treatment at UBC graduate orthodontics clinic. When compared to BWRs, NIRI technology had a higher accuracy of 97% in detecting healthy, caries-free proximal surfaces and a much lower accuracy of 60% in detecting proximal surfaces with early enamel caries. The results suggest that NIRI technology has potential as a non-ionizing screening tool for the detection of proximal surfaces without enamel caries in permanent teeth. v Preface The present study was conceptualized by Dr. Sandra Khong Tai. The study design and methodology were developed and refined with inputs from Drs. Sharmila Arjunan, Edwin Yen, Sandra Tai, Jolanta Aleksejuniene and Kavita Mathu-Muju. The research grant proposal to Align Technology was developed with contributions from all the above-mentioned research supervisors. The application for clinical ethics approval was done by Dr. Sharmila Arjunan and Dr. Jolanta Aleksejuniene. This study was reviewed and approved by the University of British Columbia Clinical Research Ethics Board per approval number H21 – 01011. Dr. Sandra Tai and Dr. Edwin Yen were instrumental in negotiating the terms and conditions of the grant with Align Technology Inc and procuring the 5D element iTero scanners for the data collection. Patient recruitment from UBC Graduate Orthodontics clinic was done by Dr. Sharmila Arjunan with assistance from the Graduate Orthodontics Clinical Coordinator, Ms. Michele Wong. Data collection for analysis was done by Sharmila Arjunan. Collection of the research data was done independently by two examiners, Dr. Kavita Mathu-Muju and Dr. Neeraja Ramadurai. Statistical analysis, tabulation of results and conclusions were done by Dr. Sharmila Arjunan with guidance from Dr. Jolanta Aleksejuniene. The thesis writeup was done by Dr. Sharmila Arjunan with guidance from all the MSc committee members. vi Table of Contents Abstract ......................................................................................................................................... iii Lay Summary ............................................................................................................................... iv Preface .............................................................................................................................................v Table of Contents ......................................................................................................................... vi List of Tables ................................................................................................................................ ix List of Figures .................................................................................................................................x List of Abbreviations .................................................................................................................. xii Acknowledgements .................................................................................................................... xiii Dedication ................................................................................................................................... xiv Chapter 1: Introduction ................................................................................................................1 1.1 Review of existing literature ........................................................................................... 1 1.1.1 Caries risk assessment and management protocol ...................................................... 2 1.1.2 Orthodontic treatment and caries susceptibililty ......................................................... 2 1.1.3 Diagnosis of dental caries ........................................................................................... 3 1.1.4 Near infrared imaging (NIRI) technology in caries diagnosis .................................... 4 1.2 Limitations in the existing literature ............................................................................... 6 Chapter 2: Study rationale, aims and hypotheses ......................................................................8 2.1 Rationale for the study .................................................................................................... 8 2.2 Research question .......................................................................................................... 9 2.3 Study hypotheses ............................................................................................................ 9 2.4 Study aims ....................................................................................................................... 9 vii Chapter 3: Materials and Methods ............................................................................................10 3.1 Study design .................................................................................................................. 10 3.2 Study participants.......................................................................................................... 10 3.2.1 Eligibility criteria ...................................................................................................... 11 3.2.2 Participant recruitment .............................................................................................. 11 3.2.3 Study risks/ harms ..................................................................................................... 13 3.2.4 Potential patient benefits ........................................................................................... 14 3.3 The study tests............................................................................................................... 14 3.3.1 Index test - (iTero Element 5D scanner with NIRI technology) ............................... 14 3.3.2 Clinical reference standard (bitewing radiography) ................................................. 19 3.3.3 Testing criteria for index test and reference standard ............................................... 20 3.3.4 Image evaluation by independent examiners ............................................................ 22 3.4 Analysis......................................................................................................................... 22 3.4.1 Sample size calculation ............................................................................................. 22 3.4.2 Measures of diagnostic accuracy .............................................................................. 23 Chapter 4: Results .......................................................................................................................24 4.1 STARD guidelines for reporting diagnostic studies ..................................................... 24 4.2 Sample size calculation ................................................................................................. 24 4.3 Sample population ........................................................................................................ 25 4.4 Inter- / intra-examiner agreement (reliability) .............................................................. 26 4.5 Diagnostic accuracy measures ...................................................................................... 26 4.6 Receiver Operating Characteristic (ROC) curve and Area Under the Curve (AUC) ... 28 viii Chapter 5: Discussion .................................................................................................................29 5.1 Comparison of study findings to other studies ............................................................. 29 5.1.1 Comparing different diagnostic indicators ................................................................ 29 5.1.2 ROC and AUC curves ............................................................................................... 30 5.1.3 Inter- and intra-examiner reliability .......................................................................... 31 5.2 Comparison of study methodology ............................................................................... 33 5.2.1 In-vitro vs in-vivo study designs ............................................................................... 33 5.2.2 Diagnostic threshold for proximal enamel caries (target disease) cut-off ................ 34 5.3 Study strengths and limitations ..................................................................................... 34 5.4 Suggestions for future research ..................................................................................... 40 5.5 Clinical implications of our study ................................................................................. 42 Chapter 6: Conclusions ...............................................................................................................44 References .....................................................................................................................................45 Appendix A ..................................................................................................................................51 A.1 - Adult consent form ................................................................................................... 51 A.2 - Adolescent information and assent form (14-17 years) ............................................ 59 ix List of Tables Table 3.1 The scoring criteria for the NIRI images and BWRs ................................................... 21 Table 3.2 Diagnostic accuracy testing measures used in the study .............................................. 23 Table 4.1 Key terminologies according to STARD guidelines .................................................... 24 Table 4.2 Participant demographic data ....................................................................................... 25 Table 4.3 Inter- / Intra-examiner reliability (Weighted Cohen’s Kappa Test) ............................. 26 Table 4.4 Interpretation of Cohen’s Kappa Test .......................................................................... 26 Table 4.5 Comparison between two diagnostic tests - the 2x2 contingency table ....................... 27 Table 4.6 The diagnostic accuracy indicators with formulas ....................................................... 27 Table 4.7 Area Under the Curve (AUC) interpretation ............................................................... 28 x List of Figures Figure 3.1 The iTero Element 5D scanner with near infra-red imaging (NIRI) technology ....... 15 Figure 3.2 Scanning technique with the digital image formed on the screen .............................. 16 Figure 3.3 A screen shot of the intra-oral scan of a lower arch with the NIRI image (top right) and colour image (bottom right) of the mesial surface of the lower left second molar ................ 17 Figure 3.4 Illustration of healthy and carious tooth surface on near infra-red images (NIRI) .... 18 Figure 3.5 Screen shot of mesial and distal surface of #15. The left side depicts the colour image and the right side depicts the NIRI image ..................................................................................... 19 Figure 3.6 BWR included in the study with acceptable diagnostic quality ................................. 20 Figure 3.7 NIRI and BWR images of distal surface of #35 which scored positive for proximal enamel caries by both examiners .................................................................................................. 21 Figure 4.1 Flow chart of study participants ................................................................................. 25 Figure 4.2 Receiver Operating Characteristic (ROC) Curve (blue line) ...................................... 28 Figure 4.3 Area Under the Curve (AUC) (orange shaded area) .................................................. 28 Figure 5.1 – Illustration of NIRI and corresponding BWR image of composite restoration on mesial surface of #26 .................................................................................................................... 37 Figure 5.2 – Illustration of NIRI and corresponding BWR image of amalgam restoration on occlusal and mesial surface of #16 ............................................................................................... 37 Figure 5.3 Illustration of NIRI and corresponding BWR image of excessive saliva on the occlusal surface of #47.................................................................................................................. 38 Figure 5.4 Illustration of NIRI and corresponding BWR image of partially erupted #35 ........... 38 Figure 5.5 Illustration of NIRI and corresponding BWR image of #25 ...................................... 39 Figure 5.6 Illustration of NIRI and BWR of overlapped proximal surfaces of #45 .................... 39 xi Figure 5.7 Missing information on BWRs due to A) Cone-cut B) inappropriate film sensor positioning..................................................................................................................................... 40 xii List of Abbreviations ADA – American Dental Association AUC – Area Under the Curve BWR – Bitewing radiography BWRs – Bitewing radiographs FOTI – Fiber optic transillumination FP – False positive FN – False negative NIRI – Near Infra-Red Imaging NPV – Negative predictive value PPV – Positive predictive value ROC Curve – Receiver Operating characteristic curve Sn – Sensitivity Sp – Specificity STARD – Standard for Reporting of Diagnostic Accuracy Studies TN – True negative TP – True positive UBC – University of British Columbia WHO – World Health Organization WSL – White spot lesions xiii Acknowledgements “The hardest arithmetic to master is that which enables us to count our blessings.” Eric Hoffer This thesis is a result of the guidance and advice that I was privileged to receive from many people, whose contribution in assorted ways deserve special mention. I start with my deep sense of gratitude to Dr. Edwin H.K Yen, my research supervisor and program director. His exceptional knowledge, clinical acumen and calm demeanor have enriched my growth as an Orthodontist. Sir, I am indebted to you more than you know. My sincere gratitude to Dr. Sandra Khong Tai for her unwavering support and inspiration. Her wholehearted involvement and guidance shaped this project to its present form. My earnest thanks to Dr. Jolanta Alesksejuniene for her optimistic guidance & invaluable suggestions. This thesis was not possible without her critical contribution, especially in statistics and multiple manuscript preparations. My deep sense of gratitude to Dr. Kavita Mathu-Muju for all the assistance and kind words of encouragement. Thank you for painstakingly dedicating many hours to evaluate the data. I am thankful to Dr. Amanda Sigouin, Dr. Jessica Kehler and Ms. Michele Wong for their support with patient recruitment and to Dr. Neeraja Ramadurai for dedicating time from her busy schedule to evaluate the data. Where would I be without my family? I thank my husband Chinmay and son Hriday, for being my anchors through this arduous undertaking called residency. I am grateful to my family including my parents, in-laws and sister for their unwavering support. xiv Dedication No matter how testing the times have been No matter how turbulent the journey ahead The twinkle in your eyes and sparkle in your smile Is all the reassurance I will ever need This thesis is dedicated to my son, Hriday! The last three years were defined by his efforts and sacrifices as much as mine. 1 Chapter 1: Introduction The 'Global oral health status report - Towards universal coverage for oral health by 2030' published by the World Health Organization (2022) highlights the importance of oral health as an integral part of an individual's general well-being. Untreated dental caries is one of the major oral diseases impacting around 3.5 billion individuals worldwide. A closer look at the trends indicates that there is a steep increase in caries prevalence rate in the early teenage years of an individual. It is also noted that there is a shift in occurrence of caries from the occlusal to proximal surfaces over the years (1). Government and private organizations spend approximately US$390 billion annually to meet oral health care needs of the population, a considerable portion of which is spent on treating dental caries in more advanced stages (2). Visual-tactile and radiographic examination methods are extensively discussed as screening tools to detect dental caries. Since they both do not have a perfect sensitivity and specificity rate, they cannot be considered a gold standard for detection of non-cavitated initial enamel caries. Moreover, the frequent use of ionizing radiation can be of concern in vulnerable populations like pregnant women and growing children (3-5). Caries management protocols heavily rely on accurate diagnosis; hence it is important to scientifically assess the diagnostic abilities of both contemporary and conventional methods of caries diagnosis with minimal possible harm to the patient. 1.1 Review of existing literature In clinical practice, caries risk assessment of an individual is crucial in determining the most appropriate treatment protocol. Comprehensive evaluation should include detailed history and clinical examination followed by supplemental radiographs, as indicated. The following 2 section briefly reviews pertinent literature regarding the effect of caries risk assessment on caries management protocols. 1.1.1 Caries risk assessment and management protocol Various organizations have published detailed tools for caries risk assessment including the American Dental Association (ADA), Caries Management by Risk Assessment (CAMBRA) group, and the American Academy of Pediatric Dentistry (6-9). Fontana et al., indicated that some clinical factors like visual/ radiographic carious lesions in the last 24 months, missing teeth due to caries, visible plaque, inadequate salivary flow and orthodontic appliances could potentially present with moderate/ high risk for future caries development (6). Based on the best-practice review published by the American Academy of Pediatric Dentistry (2022), moderate and high caries risk patients need to be recalled every 3-6 months for dental check-up and radiographic assessment every 6-12 months. The proposed treatments include fluorides (0.5% in toothpaste, drinking fluoridated water and professional topical application of fluoride every 3 months), dietary counseling and sealants for non-cavitated carious lesions. Larger cavitated lesions are to be treated with minimally invasive modalities which include step-wise excavation of soft dentin (9,10). Thus, it is important to diagnose dental caries at more incipient stages in order to prevent more extensive, time consuming and complex treatment at the more advanced stages. 1.1.2 Orthodontic treatment and caries susceptibility Orthodontic appliances combined with inadequate oral hygiene measures have been suggested as a risk factor for developing new carious lesions (11-14). Sundararaj et al., 3 conducted a meta-analysis evaluating the occurrence of white spot lesions (WSL) in patients undergoing fixed orthodontic treatment and concluded that there was a 68.4% prevalence rate of WSLs (11). A prospective clinical study conducted by Al Mulla et al., and a review by Walsh LJ et al., suggest that high caries risk patients before the commencement of orthodontic treatment had higher caries susceptibility. The enamel demineralization was mainly attributed to the higher quantity of microbes such as - Streptococci Mutans and Lactobacilli (12,13). Fixed orthodontic treatment has known to be a hinderance for flossing of interdental surfaces. Kim SJ et al., reported that patients who did not floss their teeth regularly had a 1.46 times higher chance of developing proximal surface caries (14). Since orthodontic treatment generally takes between 12-30 months in duration, it is important to evaluate patients with high caries tendency and inadequate oral hygiene measures including regular flossing of interdental surfaces. This supports the need for testing of devices that detect early proximal caries and periodic monitoring of lesions with minimum risk to the patient. 1.1.3 Diagnosis of dental caries It is crucial to compare the diagnostic accuracy of caries detection methods to a ‘gold standard’ which is considered to be accurate and precise in identifying the patho-anatomical aspect of dental caries. Wenzel et al., recommended microscopic examination of ground sections of teeth as the ‘gold standard’ in caries diagnosis (3). It is noteworthy that a ‘gold standard’ is not applicable in all clinical scenarios, especially where the dental caries is in incipient stages and the teeth are not indicated for extractions. Walsh et al., described some approaches to design a study 4 in the absence/ inability to apply the ‘gold standard’ including using multiple reference standards with lesser sensitivity and specificity values for validation of caries detection (15). Bader et al. published a systematic review describing different diagnostic tests including visual, visual-tactile, radiographic, electrical conductance, fiber optic transillumination (FOTI) and laser fluorescence. Probing, visual examination and radiography were the most common methods of caries detection in routine clinical practice (16). Baelum et al., reported that visual-tactile examination of contacting inter-proximal surfaces with a true-positive rate of 34.2% and false-positive rate of 1.5% was by far the superior diagnostic method over a combination of visual-tactile and radiographic methods resulting in correct clinical management decisions validated by separating the teeth and assessing for cavitation (5). Tooth separation for visual-tactile examination of caries might not be feasible in all circumstances and often times is not part of standard patient care in a clinical set up due to patient discomfort and added patient appointments (17). Bitewing radiography traditionally has higher specificity and lower sensitivity in detecting approximal dental caries. It could be attributed to the fact that caries restricted to enamel was not radiographically discernable until approximately 30-40% of enamel demineralization occurred (18,19). There is also an added risk of frequent radiation exposure which is a concern in vulnerable populations like pregnant women and growing children (20). 1.1.4 Near infra-red imaging (NIRI) technology in caries diagnosis Given the drawbacks of traditional diagnostic methods in incipient caries detection, there is the need for validation studies testing other non-invasive methods of caries diagnosis like near infra-red imaging technology (21,22). Initially patented by Daniel Fried and Robert Jones in 5 2006, near infrared transillumination uses light in the wavelength between 780-1600 nm. The optical properties of demineralized areas differ from normal tissues which causes the light to scatter leading to darker areas on images. Some commercially available devices that use this technique for detection of incipient caries include Diagnocam, Vista-Cam and Carivu (23,24). Multiple studies have compared the diagnostic accuracy of near infrared imaging of these devices with more traditional caries diagnosis methods. Some of the studies compared the diagnostic accuracy of NIRI with BWRs in isolation (25), while multiple others compared NIRI with a composite reference standard (26-31). The general consensus is that the diagnostic accuracy of NIRI was comparable to BWRs in detection of early enamel caries in the proximal contact areas. Baltaciouglu et al., conducted a retrospective study to diagnose initial enamel lesions in the proximal surfaces of 52 posterior teeth using NIRI and Phosphor plates BWRs. No significant differences were found between the two testing methods concluding that NIRI has sufficient diagnostic accuracy for detecting initial enamel lesions (25). Another in-vitro study by Lederer et al., included 100 extracted human teeth comparing near infra-red reflection of VistaCam with BWRs and validated the results with μCT as a gold standard. For both BWRs and near infra-red reflection, the sensitivity values for enamel lesions were lower at 13% and 31% respectively. The specificity value was higher than 94% for both methods (28). Stratigaki et al., assessed 116 non-cavitated proximal surfaces, and reported that the sensitivity of initial dentin lesions was 92% for NIRI, which increased to a 100% in detecting deeper dentin lesions. When compared to BWRs the initial dentin lesions showed a sensitivity of 81% with 74-100 % range when detecting deeper dentin lesions. On the other hand, the specificity seemed to be lower for 6 NIRI when diagnosing early dentin lesions (38%) as compared to BWRs with specificity of 65% (30). 1.2 Limitations in the existing literature The iTero Element intra oral scanners are primarily marketed by Align Technology Inc. The device uses class I lasers to record both 3D intraoral and 2D colour images of different dental structures for the purpose of digital impression taking in orthodontic offices. The latest edition of these scanners, the iTero Element 5D intraoral scanners, launched in 2019, has an added feature of near infrared imaging (NIRI) technology for the diagnosis of proximal surface dental caries. This imaging system uses electromagnetic spectrum of wavelength 850nm which depends on the scattering co-efficient of light on different parts of the tooth structure (32,33). Align technology Inc. claims that this feature, like other commercially available near infrared imaging devices, is non- invasive and non-ionizing in nature. Hence, NIRI can be used to diagnose and monitor early enamel lesions in the proximal surfaces in orthodontic patients in addition to enabling patient chair side education. To the best of our knowledge, at the time of starting the current research study in 2020, there were no published articles on the diagnostic efficacy of NIRI technology of iTero Element 5D intraoral scanners in detecting incipient proximal surface dental caries. However, two subsequent studies were published by Litzenburger et al., and Metzger et al., in 2022 comparing the diagnostic efficacy of NIRI technology of iTero 5D Element scanners in detecting proximal surface dental caries (34,35). Both the studies had different clinical settings and methodologies from our current study. The Litzenburger et al., used an in-vitro study design with an advantage of validating the results with µCT imaging but does not replicate the accurate clinical conditions. 7 The Metzger et al., is a multi-center study with an in-vivo study design with greater involvement from Align Technology Inc. in data assessment. It is important to test NIRI technology of iTero Element 5D intra oral scanners in different clinical settings and patient populations in order to add to the scientific literature. This is imperative in helping potential dentists and orthodontists to make an evidence-based decision on using this particular feature of the iTero 5D Element scanners to make clinical decisions on caries management. 8 Chapter 2: Study rationale, aims and hypotheses 2.1 Rationale for the study With the advent of non-invasive technologies, there has been an increased emphasis on detecting dental caries in the early stages of progression in order to avoid expensive and time-consuming treatment later on. The need for early diagnosis is also relevant in orthodontic patients who have moderate/ high caries risk. Intra-oral BWRs have been the traditional method for detecting inaccessible proximal surface carious lesions. Though considered the clinical reference standard, BWRs do not have a perfect sensitivity and specificity, hence BWR cannot be considered a gold standard. Also, BWRs use ionizing radiation which have adverse effects on children and pregnant women. Near infra-red imaging technology has been available to dentists to aid in detecting dental caries on occlusal and proximal surfaces. Some of the devices available to dentists include Diagnocam, CariVu and Vistacam. Previous studies have documented the diagnostic accuracy of detecting occlusal and proximal caries with these devices. iTero scanners have been used widely in orthodontic practices for digital impression taking. The latest iTero Element 5D scanner with in-built NIRI technology for proximal surface caries detection were tested by few authors thus far using different methodologies. The current study assessed the diagnostic testing ability of NIRI technology in detecting early interproximal caries lesions with an in-vivo study design replicating the clinical set-up as much as possible. 9 2.2 Research question How does the diagnostic accuracy of the near infra-red imaging of iTero Element 5D intra oral scanners (index test) compare with bitewing radiographs (clinical reference standard) in the detection of proximal surface enamel caries (target condition) in individuals ≥12 years of age? 2.3 Study hypotheses • The diagnostic accuracy measures of the index test are higher than or equal to the clinical reference standard in detecting the target condition in individuals ≥12 years of age. • The index test can be used as a triage test before taking bitewing radiographs in the caries detection clinical pathway. 2.4 Study aims • To compare the diagnostic ability of the index test to the clinical reference standard in detecting early caries on proximal tooth surfaces in the subjects ≥12 years of age. • To evaluate the inter- and intra-examiner reliability of both tests. • To determine if the index test can be used as a non-ionizing triage test in the clinical pathway for diagnosing the target condition. 10 Chapter 3: Materials and Methods This study follows the protocols elaborated in the Standards for Reporting of Diagnostic Accuracy Studies (STARD) and Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) guidelines (36-39). 3.1 Study design For the current clinical diagnostic study, the participants were recruited prospectively where the study design and data collection were planned before patient recruitment. The Ethics approval for the study was obtained from the University of British Columbia (UBC) Clinical Research Ethics Board (# H21-01011). The same eligibility criteria applied to all participants. Eligibility criteria were assessed by the co-investigator, Dr. Sharmila Arjunan. The consenting subjects received both the index test and the clinical reference standard test. 3.2 Study participants The study was conducted at the University of British Columbia (UBC) Faculty of Dentistry’s Graduate Orthodontics Clinic located at the Nobel Biocare Oral Health Centre in Vancouver, BC, Canada. All individuals ≥ 12 years of age with mixed/permanent dentition presenting at the UBC Faculty of Dentistry for orthodontic treatment in the period between September 2021 to January 2022 were invited to participate. 11 3.2.1 Eligibility criteria Inclusion criteria • Healthy patients with the ASA status 1 (American Anesthesiologists Association) who need orthodontic treatment • Patient’s age 12+ years with mixed/ permanent dentition with permanent first molars present and having 1+ non-cavitated and non-restored interproximal surface(s) on clinical examination • No fixed orthodontic appliances at the time of data collection • Patients able to provide informed consent. Consent was taken from parents or primary caretakers in case of children who lacked capacity to provide consent on their own. Exclusion criteria • Patients and children whose guardians (in case of minors) did not consent to participate in the study. • Patients who did not require diagnostic records (including bitewing radiographs and intra-oral scans) taken at the start of their orthodontic treatment. • Patients who could not have bitewing radiographs or intra-oral scans taken due to a physical/ cognitive inability to co-operate. • Participants whose bitewing radiographs were of poor diagnostic quality by the data examiners. 3.2.2 Participant recruitment Study participants were recruited consecutively from a patients’ pool who presented for treatment at the UBC Graduate Orthodontics clinic between September 2021 to January 2022. 12 Procedures followed before the screening appointment – COVID-19 safe research and clinical protocols followed the British Columbia Dental Association guidelines and safety protocols. Patients scheduled for routine screening appointments were contacted by phone/email for COVID screening about 2 days prior to their visit as part of our normal clinical protocol. During the screening appointment – Patients underwent a complete orthodontic and general dental evaluation by certified orthodontic instructors and/or graduate students following the procedural protocol prior to commencing orthodontic treatment. Ms. Michele Wong, the clinical coordinator/CDA for the Graduate Orthodontics clinic, explained the study to patients and verbally obtained their consent to be approached by a study team member. Once consent was obtained, the co-investigator Dr. Sharmila Arjunan explained the risks and benefits of participating in the study and asked to sign the necessary consent forms. Patients were informed that the research involves minimal risk and the study’s procedures are part of normal standard of care prior to starting orthodontic treatment. Consent forms were signed by prospective participants themselves if they were of legal age, and by parents or primary caretakers in case children lacked capacity to provide consents on their own. The adult and adolescent consent forms are presented in Appendices A1 & A2 respectively. Once consent was obtained, the participants were informed that they still had the right to withdraw from the study at any point in time via written communication to the co-investigator. $20 gift cards were provided to patients as a token of appreciation for participating in the study. 13 Appointment for taking records - The study required the following information from data/records to be collected within a period of 4 months – • Demographic data – name, age (in years), and sex. • Clinical assessment by visual-tactile method for evaluation of cavitation of proximal surfaces. Only non-cavitated surfaces were included in the study. • Digital intra-oral bitewing radiographs including the distal surfaces of canines to the distal surfaces of the last erupted molars in all four quadrants. • Digital intra-oral scans taken with the iTero 5D Element scanners which are specially equipped with Near Infra-Red Imaging (NIRI) technology. The above information was obtained either during the screening appointment or in subsequent visits before starting orthodontic treatment, and no extra costs were incurred by the participants. If bitewing radiographs were taken by the participants’ general dentist within the last 4 months, the radiographs were requested from the private practices with the participant’s consent. 3.2.3 Study risks/ harms This is a minimal risk study with a direct benefit to the patients as intraoral scans are standard care at the pre-orthodontic diagnostic phase. The participants were informed that all patients will have scans done irrespective of their participation in the research study. The scans are non-invasive and the NIRI technology in the scanners use non-ionizing radiation which might be a minimal discomfort to patients but this usually is well tolerated even by younger individuals. 14 Bitewing radiographs are the current standard of care for detecting clinically caries on inaccessible proximal contact areas. The patients might experience mild discomfort while placing the sensor holder in the mouth, but this is usually well tolerated by most patients. 3.2.4 Potential patient benefits The intraoral scans are primarily used as digital impressions for diagnostic and patient education purposes. The NIRI imaging technology in the latest iTero 5D Element scanners also provides a non-ionizing method of detecting early proximal surface caries. The NIRI for detecting dental caries in other commercially available devices was validated in several studies. Before starting orthodontic treatments, patients receive full mouth series of radiographs to detect proximal/occlusal surface caries. Early detection of such lesions is highly recommended prior to the start of orthodontic treatment. 3.3 The study tests 3.3.1 Index test – (iTero Element 5D scanner with NIRI technology) The iTero scanners are manufactured by Align Technology Inc, Tempe, AZ, USA, and their primary application is to record full-mouth digital impressions (Figure 3.1) 15 Figure 3.1 The iTero Element 5D scanner with near infra-red imaging (NIRI) technology. The latest iTero Element 5D scanner is an intra-oral digital imaging system with improved features which allow scanning at the rate of 6000 frames per second, which is about 20 times faster than in the earlier models. The intra-oral scanning technique is explained by the manufacturer through demonstrative videos posted on their website www.itero.com. The scanner is easy to use and requires minimal training. The scanning technique is shown in Figure 3.2 16 Figure 3.2 Scanning technique with the digital image formed on the screen. The iTero Element 5D scanner has the facility to capture both, the 3D colour images and near infra-red images of the dentition (Figure 3.3). 17 Figure 3.3 A screen shot of the intra-oral scan of a lower arch with the NIRI image (top right) and colour image (bottom right) of the mesial surface of the lower left second molar The in-built near infra-red imaging (NIRI) technology uses wavelength of 850 nm in the electromagnetic spectrum of 0.7 to 2.0 μm. The translucency of the tooth material to NIRI light is related to the brightness level of the image that is captured. The higher the translucency, the darker the image. Healthy enamel is translucent to NIRI light on the image appearing dark, whereas dentin and carious enamel are reflective, which tends to scatter the NIRI light and their images appear brighter than of the healthy enamel (Figure 3.4). 18 Figure 3.4 Illustration of healthy and carious tooth surface on near infra-red images (NIRI) Preparation for the NIRI images assessment The full-mouth digital scans taken using the iTero Element 5D scanner are stored in the iTero.com website which can be accessed using a password protected account. In preparation for data analysis, individual screen shots are taken of each proximal surface from the distal surface of the canine to the distal surface of the last erupted molar in each quadrant. Each surface has a number coded for identification as shown in Figure 3.5 19 Figure 3.5 Screen shot of mesial and distal surface of #15. The left side depicts the colour image and the right side depicts the NIRI image 3.3.2 Clinical reference standard (bitewing radiography) In-vitro histologic microscopic examination is considered the gold standard for detecting caries (3). However this method is not feasible in an in-vivo study. Furthermore, other methods described for detection of proximal surface caries like visual and visual – tactile examination have reported lower sensitivity and specificity values. These methods appear to be more effective for cavitated proximal caries. For initial enamel caries in proximal surfaces, bitewing radiographs so far, have the highest sensitivity and specificity values of 41% and 78% respectively (16). Therefore, for the current study BWR was chosen as the clinical reference standard. Once eligibility criteria were fulfilled, consenting individuals had digital BWRs taken 20 according to American Dental Association (ADA) recommendations. The BWRs were adjusted for horizontal/vertical angulation so that there was minimal overlap of the proximal surfaces. This way, the distal surface of the canines to the distal surface of the last erupted tooth were captured. A sample BWR is shown in the figure below: Figure 3.6 BWR included in the study with acceptable diagnostic quality The BWRs were taken at the UBC Graduate Orthodontics clinic or retrieved from the participants’ dental charts if taken within the last 4 months. The examiners assessed the quality of the BWRs for the quality. 3.3.3 Testing criteria for index test and reference standard The diagnosis of enamel caries was done using the modified scoring system suggested by Ismail et al., (40) shown in the table below: 21 Table 3.1 The scoring criteria for the NIRI images and BWRs The following figure shows a NIRI image and colour clinical image and BWR of a proximal surface, all scored positive for caries. Figure 3.7 NIRI and BWR images of the distal surface of #35 which scored positive for proximal enamel caries by both examiners 22 3.3.4 Image evaluation by independent examiners Two pediatric dentists were briefed about the study and were informed by the principal investigator, Dr. Sharmila Arjunan, on the scoring criteria for BWRs and NIRI images. For standardization, the examiners individually scored 5 randomly selected proximal surfaces for both BWRs and NIRI images, subsequently their scoring findings were discussed for uniformity. The image assessments were done independently by the two examiners for detection of proximal caries on BWRs and NIRI images. The examiners were blinded to the results of the two different images being evaluated. A binominal scale was used for diagnostic threshold – score 0 for no caries and a score 1 for incipient enamel caries. Images deemed to be of poor diagnostic quality by the examiners were removed from the assessment. Any disagreements in results were solved by a mutual consensus. Indeterminate findings were also excluded from the final analysis. To determine the inter- and intra- rater agreement, randomly selected 25 interproximal surfaces were re-examined independently by the two examiners two weeks after the first scoring. 3.4 Analysis 3.4.1 Sample size calculation The calculation of minimal sample size was based on the primary data of approximately 40 patients. The sample size calculation required an estimate of the prevalence rate of proximal surface caries in the sample population. The sample size pre-determined tables by Bujang et al. to calculate the minimum sample size by using the Power Analysis and Sample Size (PASS) software with specified type I errors, power of the study and the effect size were used (41). 23 3.4.2 Measures of diagnostic accuracy The accuracy of the diagnostic tests is commonly indicated by the following measures: sensitivity (SE), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) (42). The description of these indicators is presented in the table below: Table 3.2 Diagnostic accuracy testing measures used in the study Diagnostic accuracy measures were tabulated in a 2x2 contingency table. A weighted Cohen’s Kappa test was applied to assess the inter- and intra-examiner reliability. The Receiver Operating Characteristic (ROC) and the Area Under the Curve (AUC) were calculated to measure the test’s discriminatory ability based on various diagnostic thresholds. Statistical analysis was conducted using the SPSS 27.0 software (SPSS Inc, Chicago, IL, USA). 24 Chapter 4: Results 4.1 STARD guidelines for reporting diagnostic studies The terminologies according to STARD guidelines and the corresponding explanations are illustrated in the following table: Table 4.1 Key terminologies according to STARD guidelines 4.2 Sample size calculation The sample size calculation was done after primary data collection. According to the tables formulated using Power Analysis and Sample Size (PASS) software by Bujang et al., the following parameters were used (41): • Disease (inter-proximal enamel caries) prevalence – 5.8% • Sensitivity and specificity for the null hypotheses – 50% • Sensitivity and specificity proposed in the alternate hypotheses - >50% • Value of power of screening test – 80% and p -value of 0.044 The estimated minimum sample size was – • N = 980 a minimum number of total inter-proximal surfaces scored • N1 = 49 a minimum number of surfaces with disease (initial enamel caries) 25 4.3 Sample population The flow chart of the study participants is depicted in Figure 4.1. The demographic data of the participants who met the eligibility criteria and were included in the study is shown in Table 4.2 - Figure 4.1 Flow chart of the study participants Table 4.2 Participant demographic data 26 4.4 Inter-/ intra-examiner agreement (reliability) The inter- and intra- examiner reliability for BWRs and NIRI images were assessed using the Weighted Cohen’s Kappa test (Table 4.3 and 4.4). The degree of examiner agreement was ‘good’ for the BWR and ‘very good’ for NIRI imaging. Table 4.3 Inter- / intra-examiner reliability (Weighted Cohen’s Kappa Test) Table 4.4 Interpretation of Cohen’s Kappa Test 4.5 Diagnostic accuracy measures Tables 4.5, 4.6 and 4.7 explains the standard diagnostic accuracy measures used for testing the efficiency of detecting inter-proximal enamel caries as compared to the clinical reference standard. 27 Table 4.5 Comparison between two diagnostic tests - the 2x2 contingency table Table 4.6 The diagnostic accuracy indicators with formulas 4.6 Receiver Operating Characteristic (ROC) Curve and Area Under the Curve (AUC) ROC is a probability curve and AUC represents the degree/ measure of separability. The ROC- AUC Curves explain the extent to which the test is capable of distinguishing between inter-proximal surfaces with and without initial enamel caries. 28 Figure 4.2 Receiver Operating Characteristic (ROC) Curve (blue line) Figure 4.3 Area Under the Curve (AUC) (orange shaded area) In the current study, the value for the Area Under the Curve (AUC) was 0.789 which can be considered acceptable in terms of the test’s ability to diagnose surfaces with and without caries. Table 4.7 Area Under the Curve (AUC) interpretation 29 Chapter 5: Discussion 5.1 Comparison of study findings to other studies 5.1.1 Comparing different diagnostic indicators Sensitivity, specificity, positive predictive value, and negative predictive value are commonly recommended diagnostic accuracy indicators (42). In our study, we assessed a total of 1110 inter-proximal surfaces of posterior teeth, of which 65 surfaces were diagnosed as caries positive for initial enamel caries in BWRs by both the examiners. NIRI technology when compared to the clinical reference standard of BWRs showed a relatively low sensitivity of 60%, but a higher specificity of 97.7% with positive and negative predictive values being 61.9% and 97.5% respectively. Our results indicate that NIRI technology better identified proximal surfaces without enamel caries (true negatives) than the surfaces with enamel caries (true positives). There are two previous studies that tested NIRI technology of iTero 5D Element scanners in assessing incipient proximal enamel caries. The in-vivo study of 3499 proximal surfaces showed a sensitivity of 51.6% and specificity of 90.4% in detecting early enamel caries. In contrast, the sensitivity and specificity of caries involving the dentino-enamel junction was much higher at 84.8% and 97.1% respectively (35). The second iTero in-vitro study assessed the diagnostic accuracy of NIRI technology compared to BWRs and validated it with micro-computed tomography in lingual, buccal and occlusal surfaces of 250 permanent teeth. This study reported specificity of NIRI technology at 83-89% and lower sensitivity values of 26-42% for diagnosing caries in molars and premolars. The results of both studies are similar to our findings in terms of lower sensitivity and higher specificity in detecting proximal contact area enamel caries. 30 Other researchers conducted studies to assess the diagnostic accuracy of near infra-red imaging technology incorporated in other commercially available devices. For detecting proximal surface enamel caries, Takorova et al. study reported that the diagnostic accuracy of NIRI technology in DiagnoCam was more similar to BWRs than visual-tactile examination (29). Lederer et al. (2019) in-vitro study assessed diagnostic ability of NIRI technology in VistaCam iX HD in detecting interproximal enamel caries, and reported that NIRI for detecting early enamel lesions had lower sensitivity at 13% but higher specificity at 94% (28). NIRI technology of iTero 5D Element scanners has better efficiency in detecting proximal surfaces without initial enamel caries than detecting proximal surfaces with initial enamel caries. It has the potential of being used as a clinical screening tool in patients to detect caries free enamel proximal surfaces. Based on this initial assessment, the clinician can then prescribe BWRs to further assess proximal surfaces that have suspected initial enamel caries lesions. It is especially beneficial in orthodontic patients with higher caries risk, and vulnerable populations like growing children and pregnant women where frequent exposure to radiation is a matter of concern. 5.1.2 ROC and AUC curves The Receiver Operating Characteristic (ROC) curve is the performance measurement of how well a diagnostic test can distinguish between the presence and absence of the target condition. The ROC is the probability curve while the Area under the Curve (AUC) predicts the degree of separability between the two diagnoses (surfaces with enamel lesions and surfaces without enamel lesions). In our study, we obtained an ROC-AUC curve value of 0.789. Values between 31 0.7 to 0.8 are considered acceptable. This finding indicates that NIRI technology of iTero Element 5D scanners are able to detect proximal enamel caries with acceptable accuracy. The in-vitro Litzenburger et al. (2021) study compared the diagnostic ability of NIRI technology of iTero Element 5D scanners with BWRs and micro-computed tomography showed an AUC value of 0.63 for detecting caries on the occlusal, buccal and lingual surfaces of posterior teeth (34). Furthermore, Baltacioglu et al. (2017) assessed the diagnostic ability of the custom-made NIRI camera and compared it with digital phosphor plated BWRs (25). The authors reported an AUC value between 0.78 to 0.83 which was marginally higher than the values reported in our study. The results of our study in comparison to other studies all reported an AUC value between 0.7 to 0.8. This indicates that NIRI technology as a caries detection method is able to distinguish between proximal contact areas with and without enamel caries with acceptable certainty. 5.1.3 Inter- and intra-examiner reliability In our study, the inter- and intra-examiner reliability was calculated using the Cohen’s Kappa test. The intra-examiner reliability for BWRs was 0.852 and for NIRI images was 1.00. Both the values showed a very good degree of agreement based on the inference scale for the Cohen’s Kappa test. The inter-examiner reliability for BWRs was lower at 0.789 and for NIRI images was much higher at 0.975. Assessment of the BWRs showed good degree of agreement, whereas evaluations of the NIRI images showed very good degree of agreement. In conclusion, it appears that NIRI images are more likely to be interpreted with better agreement and BWRs interpretation showed more overall variability. 32 In this regard, the results of other studies are in agreement with our findings. Litzenburger et al. (2021) reported the inter-rater reliability of NIRI technology of iTero Element 5D scanners as 0.96 and for BWRs as 0.85. In addition, he evaluation of NIRI images was more reproducible by different examiners (34). The Metzger et al. (2021) multi-center prospective clinical study reported a much lower kappa coefficient of 0.24 for detecting early enamel lesions using NIRI technology of iTero Element 5D scanners when assessed by five individual dentists (35). The inter-examiner kappa coefficient increased to 0.51 for the same data when examined by an expert team trained in assessing NIRI images. The results support the claim that the interpretation of NIRI images tends to be more reproducible with examiner experience. The Lederer et al. (2019) study showed a very good inter-examiner agreement in interpreting BWRs (Cohen’s Kappa value of 0.93) and NIRI images (Cohen’s Kappa value of 0.89) with BWR assessment having a slightly higher value than NIRI (28). The intra-examiner values were similar for both methods (0.84-0.89). Baltacioglu et al. (2017) reported good intra-rater agreement between NIRI images than for phosphor plated BWRs with kappa coefficients ranging from 0.55-0.64 for BWRs and much higher values of 0.79-0.88 for NIRI images (25). Stratigaki et al. (2020) conducted an in-vivo testing of the NIRI technology of DiagnoCam. The study results were different from ours. Their inter- and intra-examiner reliability for BWRs was 0.63 and 0.76-0.87 respectively. The inter- and intra-examiner reliability for NIRI images was much lower at 0.51 and 0.62-0.68 respectively. But the authors also reported that inter- and intra-examiner reliability for NIRI images considerably increased to 0.54 and 0.76 to 0.89 respectively. The increase in agreement might be attributed to learning curve related to more training in the use of this tool (30). 33 A better examiner agreement in inferring NIRI images than BWRs suggests that NIRI technology of iTero 5D Element scanners is a simple to use tool. There are multiple articles and iTero product catalogues available for training practitioners in the use of this technology in assessing proximal surfaces for either the presence of absence of enamel caries. Unlike BWRs, there was lesser inter and intra-examiner variation of interpretation. 5.2 Comparison of study methodology 5.2.1 In-vitro vs in-vivo study designs Literature shows that in-vitro and in-vivo human and animal studies have been used to assess the accuracy of caries detection methods. Our study was conducted using an in-vivo study design to diagnose enamel proximal contact area caries. The effects of saliva, dietary habits, oral hygiene and type of dentition may potentially influence the study results. Since the NIRI technology of the iTero Element 5D scanners has potential for clinical use in making critical decisions on caries management, it is important to evaluate the diagnostic accuracy of this device in similar conditions. Most of previous studies used an in-vivo study design to test diagnostic accuracy of various commercially available near infra-red imaging devices (25-27,29-31). In-vitro study designs attempt to replicate the clinical environment in controlled laboratory conditions. Findings from such studies might be less reliable and not completely translatable to human beings. The advantage of this study design in caries detection is the ability to apply the gold standard of histopathological assessment of extracted human teeth (28,34). 34 5.2.2 Diagnostic thresholds for proximal enamel caries (target disease) cut-off Untreated dental caries in permanent dentition is one of the major global public health concerns. Governments and private organizations around the world spend billions of dollars annually in treating dental caries in more advanced stages (1). Various caries management protocols recommend a conservative approach including frequent recall visits every 3-6 months, active surveillance of non-cavitated carious lesions and sealant application for moderate to high caries risk individuals (6,9). There is a growing interest in evaluating the efficiency of non-invasive techniques in detecting caries at the early stages of its development. Traditional caries detection methods showed low diagnostic accuracy. For example, the sensitivity and specificity of visual-tactile examination for analyzing cavitated proximal lesions were 52% and 98% respectively. Meanwhile, for non-cavitated enamel lesions on the proximal surfaces, radiographic examination is considered as most reliable method despite sensitivity and specificity values being 41% and 78% respectively (16). In our study, we assessed the diagnostic accuracy indicators of NIRI technology and compared it to BWRs considering it to be a gold standard. But based on the results of other studies, we acknowledge that BWRs do not have a perfect sensitivity and specificity in detecting enamel lesions due to which there is a probability for a reference standard bias in our study. 5.3 Study strengths and limitations Strengths This study included standard clinical practices in terms of patient recruitment and clinical procedures performed prior to starting orthodontic treatments i.e., taking digital scans and 35 BWRs, subsequently interpreting them. The study employed a prospective design where the participants were consecutively recruited and subsequently enrolled. The index test and the clinical reference standard were interpreted independently by examiners without the knowledge of the results of the other. The time interval between the index test and the clinical reference standard was limited to 4 months, based on the fact that carious lesions take much longer to progress. Testing cut-offs in terms of extent of caries progression were clearly specified at the start of the study. Limitations – Reference standard bias – The study used an imperfect clinical reference standard (BWRs). Our in-vivo clinical study evaluated the presence of initial enamel caries in human subjects, consequently choosing the gold standard (histopathological assessment of extracted teeth) was not feasible, as gold standard requires teeth being extracted (3). Clinical guidelines published by the American Academy of Pediatric Dentistry recommend active surveillance for non-cavitated initial enamel lesions. In addition, excavation of the carious defect to clinically validate the results of the reference standard was not possible in our study. The use of a composite reference standard was also not feasible in our study unlike suggested by some researchers (27,29). Other diagnostic accuracy measures like visual and visual-tactile assessment to identify initial enamel caries in the proximal region is drastically reduced as compared to occlusal surface lesions due to limited accessibility. Separation method to visualize proximal caries is not standard clinical practice. Radiographic methods, despite the concerns of radiation exposure, are still heavily relied on for clinical assessment of carious lesions in the proximal surface (4,5). 36 Non-standardization of bitewing radiographs - The BWRs we used as the clinical reference standard were obtained from different sources. All the BWRs included in this study were taken with digital PSP sensors. Most of the patients had their BWRs taken at the UBC graduate orthodontic clinic by the same operator under the same film/sensor settings. However, the BWRs requested from private dental offices were assessed for parameters elaborated in the methodology section. Patients who fulfilled all eligibility criteria, including having BWRs of acceptable diagnostic quality, were included in the study. Similar methodology was adapted in some multicenter studies (34). Indeterminate results – In some instances, the NIRI/ BWR images had to be excluded from the study sample as they were of poor diagnostic quality in terms of enabling examination of initial enamel carious lesions in the proximal surfaces of posterior teeth. A few examples of such occurrences presented below: A. NIRI technology was not effective in visualizing tooth structure adjacent to restorations. The following figures 5.1 & 5.2 illustrate the NIRI and BWR image with proximal surface composite and amalgam restorations respectively. In comparison, the BWR images were more diagnostic of adjacent tooth structure for detecting secondary carious lesions. 37 Figure 5.1 Illustration of NIRI and corresponding BWR image of composite restoration on mesial surface of #26 Figure 5.2 Illustration of NIRI and corresponding BWR image of amalgam restoration on occlusal and mesial surface of #16 B. Excessive saliva present on the tooth surface obscured the NIRI images, which at times rendered image to be of non-diagnostic quality. This was not an issue of concern with BWRs. 38 Figure 5.3 Illustration of NIRI and corresponding BWR image of excessive saliva on the occlusal surface of #47 C. Partially erupted and subgingival lesions could not be assessed in the NIRI images, whereas the ionizing radiation property of BWRs allowed for penetration through cortical bone making the examination of tooth structure possible. Figure 5.4 Illustration of NIRI and corresponding BWR image of partially erupted #35 39 D. Despite the advanced features of the iTero Element 5D system with Indium Tin Oxide (ITO) defogging capabilities, any external marks on the wand sensor head might impact the clarity of the NIRI image. Figure 5.5 Illustration of NIRI and corresponding BWR image of #25 E. In certain instances, BWRs were deemed to be non-diagnostic either due to incorrect angulation while exposure or severe overlap of proximal surfaces due to excessive crowding of teeth as is often seen in orthodontic patients. NIRI images were advantageous in that these overlapped tooth surfaces could be clearly visualized. Figure 5.6 Illustration of NIRI and BWR of overlapped proximal surfaces of #45 40 F. Other procedural errors while taking BWRs like cone cuts and incorrect patient positioning also contributed to excluding such cases for interpretation. Figure 5.7 Missing information on BWRs due to A) Cone-cut B) inappropriate film sensor positioning 5.4 Suggestions for future research Taking into consideration the study limitations of comparing the efficiency of NIRI technology to BWRs an imperfect clinical reference standard, it is imperative to validate the diagnostic accuracy measures to the accepted gold standard which includes histopathological analysis of ground tooth structure or with μCT analysis of tooth surfaces (3). Two recent 2021 studies attempted to validate the results of NIRI technology by different methodologies from the one used in our study. The in-vitro study model (34) compared the NIRI images and BWRs of healthy and carious extracted teeth and validated their results with μCT radiographic analysis. The drawbacks of this model, like other in-vitro studies is the inability to simulate intraoral conditions. One should also consider differences in properties of viable and extracted tooth structures while scanning the teeth. The second study on NIRI technology of iTero 5D Element scanners (35) used a more elaborate multi-center prospective clinical study design. This in-vivo model included comparison of NIRI and BWRs of healthy and suspected carious teeth and 41 validated caries extending to dentin by means of clinical excavation. But this technique could not be adapted for diagnosing initial enamel lesions, as the management protocols recommend only active surveillance and preventive measures in such cases. The proposed future study design could include in-vivo comparison of near infrared imaging (NIRI) technology of iTero Element 5D scanners with clinical visual-tactile examination and BWRS intraorally on teeth indicated for extraction, followed by validation with the gold standard of microscopic examination once the teeth have been extracted. An extended search of the literature revealed a lack of studies comparimg NIRI technology to other commercially available near infra-red refractive devices like DiagnoCam, CariVu and VistaCam to assess the diagnostic accuracy in detecting proximal enamel lesions. It would be interesting to know if there is a difference in performance given that the wavelength range and basic mode of action differs in these devices. It is also important to note that the iTero Element 5D scanner is considerably more expensive than the other commercially available devices. Development of white spot lesions (WSLs) has been a major concern for orthodontists over the years. Since NIRI technology has the potential to detect initial demineralization of enamel on proximal surfaces, it would be beneficial to study if WSLs on buccal and labial surfaces around brackets can also be detected at their incipient stages. Furthermore, high caries risk orthodontic patients have an increased tendency to develop new carious lesions if proper oral hygiene measures are not adopted. Thus, it is important not only to detect incipient carious lesions but also to effectively monitor their progression. To the best of our knowledge, there are no studies 42 which utilized the non- ionizing NIRI technology of iTero Element 5D scanners to actively track the development of incipient caries. The results of our study and the other two studies (34,35) testing the efficacy of NIRI technology in iTero Element 5D scanners on permanent teeth cannot be extrapolated to primary dentition as the tooth morphology of primary teeth in terms of enamel thickness is different. It is also suggested that children below the age of 5 years usually are prone to caries. Therefore, future studies should also test the NIRI technology in primary dentition. 5.5 Clinical implications of our study NIRI technology is able to detect the absence of initial enamel caries on proximal surfaces with similar accuracy as BWRs. On the other hand, NIRI technology tends to under diagnose the presence of initial enamel caries on proximal surfaces. BWRs, which are the reference standard along with clinical examination, use ionizing radiation which has limitations in high-risk populations like growing children and pregnant women. There are instances in clinical practice where patients have refused radiographic assessment due to the same concern. It is reported in the literature that individuals with high caries risk are highly susceptible to develop new carious lesions during orthodontic treatment. The NIRI technology, which is non ionizing in nature and uses light of wavelength 850nm can be used to screen for proximal surfaces without enamel caries. In cases where there is considerable concern regarding the presence of a carious lesion on the proximal surface, further assessment with BWRs is recommended to aid in clinical decision making about management. In 43 this way, high risk patients can be screened more frequently without the detrimental use of ionizing radiation. The iTero element 5D scanners are commonly used in orthodontic practices for the purpose of taking digital impressions. This added feature of NIRI technology in the latest model of iTero scanners has the potential to be utilized for the purpose of screening high caries risk patients for healthy proximal surface enamel at more frequent intervals through the duration of orthodontic treatment. This device may also find use in general dental and pediatric practices where children are treated though the high cost of the scanner might be a drawback, especially if this device is intended to be used specifically for the NIRI technology. 44 Chapter 6: Conclusions • With high specificity and negative predictive value, NIRI technology of iTero Element 5D intra oral scanners has the potential to be used as a screening tool for the detection of proximal surface enamel caries. However, BWRs are still required to positively confirm the diagnosis of proximal enamel caries. • Near Infra-Red Imaging (NIRI) technology had a higher inter- and intra-examiner agreement for assessing proximal enamel caries as compared to Bite-Wing Radiographs (BWRs), which had slightly more variation. • Study findings support that the NIRI technology of iTero Element 5D scanners have the potential to be used for the triage of individuals with moderate/high caries risk. 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Ismail AI, Pitts NB, Tellez M, Banerjee A, Deery C, Douglas G, Eggertsson H, Ekstrand K, Ellwood R, Gomez J, Jablonski-Momeni A, Kolker J, Longbottom C, Manton D, Martignon S, McGrady M, Rechmann P, Ricketts D, Sohn W, Thompson V, Twetman S, Weyant R, Wolff M, Zandona A. The International Caries Classification and Management System (ICCMS™) An Example of a Caries Management Pathway. BMC Oral Health. 2015 Sep; 15 Suppl 1:1-13. 50 41. Bujang MA, Adnan TH. Requirements for Minimum Sample Size for Sensitivity and Specificity Analysis. J Clin Diagn Res. 2016 Oct;10(10):YE01-YE06. 42. Simundic AM. Measures of Diagnostic Accuracy: Basic Definitions. J Int Fed Clin Chem Lab Med. 2009 Jan 20;19(4):203-11. 51 Appendix A - Consent Forms A.1 Adult consent form 52 53 54 55 56 57 58 59 A.2 Adolescent information and assent form (14-17 years of age) 60 61 62
Thesis/Dissertation
eng
Craniofacial Science
Vancouver : University of British Columbia Library
Attribution-NonCommercial-NoDerivatives 4.0 International
Graduate
Yen, Edwin
Accuracy of diagnosing proximal caries using intra-oral bitewing radiographs and near infra-red imaging (NIRI) technology in iTero element 5D scanners : an in vivo study
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