{'fraction_non_alphanumeric': 0.03273609052943554, 'fraction_numerical': 0.0174233239031838, 'mean_word_length': 5.015667206915181, 'pattern_counts': {'":': 0, '<': 1, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 1, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Accuracy of linear measurements on CBCT images related to presurgical implant treatment planning: A systematic review

OBJECTIVE
The aim of this systematic review was to identify, review, analyze, and summarize available evidence on the accuracy of linear measurements when using maxillofacial cone beam computed tomography (CBCT) specifically in the field of implant dentistry.


MATERIAL AND METHODS
The search was undertaken in April 2017 in the National Library of Medicine database (Medline) through its online site (PubMed), followed by searches in the Cochrane, EMBASE, ScienceDirect, and ProQuest Dissertation and Thesis databases. The main inclusion criterion for studies was that linear CBCT measurements were performed for quantitative assessment (e.g., height, width) of the alveolar bone at edentulous sites or measuring distances from anatomical structures related to implant dentistry. The studies should compare these values to clinical data (humans) or ex vivo and/or experimental (animal) findings from a "gold standard."


RESULTS
The initial search yielded 2,516 titles. In total, 22 studies were included in the final analysis. Of those, two were clinical and 20 ex vivo investigations. The major findings of the review indicate that CBCT provides cross-sectional images that demonstrate high accuracy and reliability for bony linear measurements on cross-sectional images related to implant treatment. A wide range of error has been reported when performing linear measurements on CBCT images, with both over- and underestimation of dimensions in comparison with a gold standard. A voxel size of 0.3 to 0.4 mm is adequate to provide CBCT images of acceptable diagnostic quality for implant treatment planning.


CONCLUSIONS
CBCT can be considered as an appropriate diagnostic tool for 3D preoperative planning. Nevertheless, a 2 mm safety margin to adjacent anatomic structures should be considered when using CBCT. In clinical practice, the measurement accuracy and reliability of linear measurements on CBCT images are most likely reduced through factors such as patient motion, metallic artefacts, device-specific exposure parameters, the software used, and manual vs. automated procedures.


| Inclusion criteria
Eligibility criteria were as follows: • Studies performing linear CBCT measurements for quantitative assessment (e.g., height, width) of the alveolar bone at edentulous sites or measuring distances from anatomical structures related to implant dentistry. The studies should compare these values to clinical data (humans) or ex vivo and/or experimental (animal) findings from a "gold standard," that is, physical measurements using digital calipers and histomorphometry.
• Clinical studies with a sample size greater than 5.
• In vitro studies using human cadavers or dry skulls measuring linear distances in alveolar bone or between fiducial placed markers.
The exclusion criteria were defined as: • Studies with no control method for assessing the accuracy of linear measurements performed using CBCT.
• Studies comparing CBCT with other radiographic tests without an external control as gold standard.
• Case reports and case series with fewer than five patients.
• Linear measurements on teeth or around teeth or implants.

| Study selection process
Selection of studies was carried out in accordance with PRISMA guidelines. The initial search was formulated for maximal inclusion and high turnout. Two independent observers (G.F. and W.C.S.) analyzed the titles and abstracts of all identified reports. For the studies that appeared to meet the inclusion criteria or for which there were insufficient data in the titles and the respective abstracts to make a clear decision, the full texts of the articles were retrieved for further analysis. The final inclusion of the relevant full-text articles for evaluation was decided by consensus by the three observers (G.F., W.C.S., and M.B.).

| Data extraction process
Two reviewers (G.F. and W.C.S.) extracted relevant data according to the PICO framework using standardized data extraction tables.
Extracted data included the following: author, title, year of publication, study model, nature of the "gold standard" measure, nature of other comparator measures, study design, CBCT parameters used, inter-and intra-observer reliability/agreement, and other outcome measures related to accuracy.

| Quality assessment
The quality of clinical studies was assessed using the National
As the methodology of the included studies as well as the extracted data was inhomogeneous, a meta-analysis could not be carried out and thus only a descriptive analysis performed.

| Study characteristics
The key information of the selected studies such as study design, aim of the study, sample size, reference standards (comparator), methodology of assessment, representative outcomes, and major conclusions is presented in Table 3 .
Seven of the ex vivo studies placed the dry jaws/skulls in a container with water to simulate the effects of soft tissue for CBCT imaging Freire-Maia et al., 2017 ;Neves et al., 2014 ;Sheikhi et al., 2015 ;Torres et al., 2012 ;Vasconcelos et al., 2015 ;Veyre-Goulet et al., 2008 ), while Luangchana et al. covered the jaws entirely in acrylic resin for that purpose .

F I G U R E 1 Flowchart showing the screening process
A wide spectrum of CBCT units and acquisition parameters were used to acquire volumes (Table 4 ). Some authors investigated the effect of various exposure, acquisition, or display factors while others compared accuracy of CBCT to MSCT.

| Reference standards (comparators for linear CBCT measurements)
For the ex vivo studies, 17 of the 20 utilized histologic sectioning of the jaws followed by physical measurements with a digital caliper as a reference standard. Santana et al. ( 2012 ) used a combination of an analogue and a digital caliper on cadaver dissections to establish to extension of the anterior loop of the mental branch relative to the mental foramen. The accuracy of these measuring instruments was specified in only seven studies: Three studies described a 0.01 mm accuracy of the caliper used Sheikhi et al., 2015 ;Waltrick et al., 2013 ) and four described an accuracy of 0.02 mm (Al-Ekrish, 2012 ;Al-Ekrish & Ekram, 2011 ;Al-Ekrish et al., 2013 ;Luangchana et al., 2015 ). The two studies by Gerlach et al. ( 2013Gerlach et al. ( , 2014 on fresh frozen cadavers used histomorphometry as the gold standard. TA B L E 2 Reason for exclusion of full-text articles Publication (author, year) Reason for exclusion Li et al. ( 2016 ) Measurements performed on models printed using a CBCT data Shokri & Khajeh (2015) Does not specify or identify, which of the measured areas were edentulous Egbert et al. ( 2015 ) Uses a single dentate cadaveric mandible Tarleton ( 2014 ) Does not discriminate between samples (dentate and partially dentate hemisected dry mandibles) Uses dentate dry human mandibles Kamburoglu et al. ( 2011 ) Measures distances between anatomical landmarks. Does not specify implant dentistry-related distances (e.g., mental foramen-mental foramen) Ganguly et al.
Uses dentulous and edentulous cadaver heads; does not specify if edentulous areas are measured Fatemitabar & Nikgoo (2010) Measurements performed on dentate and edentulous segments; does not specify if edentulous areas are measured Suomalainen et al. ( 2008 ) Only one partially edentulous human dry mandible used; does not specify which edentulous areas are measured Loubele et al. ( 2007 ) Uses partially and fully edentulous dry mandibles; does not specify which edentulous areas are measured Lascala et al. ( 2004 ) Does not specify implant dentistry-related distances (e.g., mental foramen-mental foramen) TA B L E 3 General characteristics of the included studies with focus on comparison of linear measurements using CBCT vs gold standard ( n = 22) [In PDF format, this The difference of the buccolingual measurement was significant (CBCT < DC + L) Mean difference of the distance between the cortical bone and the MC for three software packages S1, OnDemand S2, KDIS 3D S3, XoranCat S1: −0.11 mm S2: −0.14 mm S3: 0.25 mm No significant differences between the measurements with the three software packages and the gold standard or among them

| Assessment of accuracy
Overall, there was no consistency in the use of an accuracy index between the gold standard and the linear measurements using CBCT in the identified studies (Table 3 ).
The mean difference was used in 12 studies ( Gerlach et al., 2013 ), and one study also presented the mean relative difference as a percentage .
The correlation between CBCT and the reference standard used was presented in six of the included studies Eachempati et al., 2016 ;Kamburoglu et al., 2009 ;Luangchana et al., 2015 ;Neves et al., 2014 ;Waltrick et al., 2013 ), and two assessed agreement Sheikhi et al., 2015 ). The mean measurement error in millimeters between the two values was calculated in two studies Sheikhi et al., 2015 ), one study presented the absolute error of the measurements in millimeters , four studies evaluated the mean

| Outcomes of assessment of accuracy
The majority of the studies reported submillimeter differences between CBCT and "gold standard" measurements without a statistically significant difference. Nevertheless, the range of differ- 0.03 to 0.6 mm, indicating that these differences were "not clinically significant," but without further analysis. However, in studies where a similar difference range was reported, these differences were determined to be statistically significant Luk et al., 2011 ).
In studies that assessed absolute error (millimeters) between the two measurements, most authors reported low values ranging from
The results of several authors show a high correlation between CBCT and the gold standard using different correlation parameters Luangchana et al., 2015 ;Neves et al., 2014 ;Waltrick et al., 2013 ). However, one author showed only moderate correlation . Kamburoglu et al. ( 2009 )

| Outcomes of assessment of reiliability (repeatability/reproducibility)
Inter-and intra-observer reliabilities were reported in most of the 22 studies included (Table 5 ). One study described performing interobserver analysis, but the results were not reported , and in three studies, data were only provided for one TA B L E 5 Descriptive analysis of the outcomes regarding assessment of reiliability (repeatability/reproducibility) in the studies included

Method of assessment Intra-examiner Interexaminer
Freire observer Torres et al., 2012 ;Vasconcelos et al., 2015 ). A variety of methods were used for to describe reliability including intraclass correlation coefficient alone or together with Cronbach ' s alpha, range in millimeters or Bland and Altman, Bland and Altman alone, the Pearson correlation coefficient alone or together with Cronbach ' s alpha or standard deviation, Cronbach ' s alpha alone or together with percentage of measurements with an absolute difference greater than 0.5 mm and respective p -value. Values for all studies reporting inter-and intra-observer were high (Table 5 ).

| CBCT imaging parameters
There was no consistency in the reporting of exposure, acquisition or display protocols used among the included studies (Table 4 ). In addition, no author reported on the standardization of these parameters with respect to the gold standard. Some authors deliberately modified selected parameters and found no effects on measurement accuracy.
This included voxel size Luangchana et al., 2015 ;Torres et al., 2012 ;Waltrick et al., 2013 ), scan times (Al-Ekrish, 2012 ; Waltrick et al., 2013 ), software used for analysis , and display monitor . Only one author investigated the use of two different CBCT units and found no difference in measurement accuracy .  Luangchana et al. ( 2015 ) reported no difference between CBCT and panoramic radiography in the mean measurement difference of vertical alveolar bone, but absolute and percentage differences were significantly less for CBCT than panoramic radiography, particularly in the mandible. These findings are supported by Eachempati and coworkers , who found a high correlation between height measurement in CBCT and panoramic radiography utilizing metallic ball markers as fiducial markers.

| Quality assessment of included studies
The majority of the included studies were ex vivo (20 of 22), and thus, a quality assessment for these studies was not performed. For the two remaining clinical studies, the NIH "Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies" was applied (Table 6 ). Domains on exposure and follow-up of this assessment tool do not apply for the current studies. Only one of the two studies reported a power description of the sample size.

| D I S C U S S I O N
Successful dental implant treatment should incorporate a thorough planning phase using an appropriate radiographic examination providing images of diagnostic quality Neves et al., 2014 ). Three-dimensional presurgical assessment is often necessary to identify vital anatomical structures (e.g., mandibular canal, maxillary sinus floor, mental foramen) and assessing the bone quantity and quality, which will maximize the potential for success of the inserted implants (Molly, 2006 ;Turkyilmaz & McGlumphy, 2008 ), and facilitate bone grafting procedures (Verdugo, Simonian, Smith McDonald & Nowzari, 2009 ). CBCT imaging is now commonplace and has become popular for diagnostic procedures, especially in implant dentistry. Compared to MSCT, CBCT provides cross-sectional and 3D imaging at reduced radiation exposure Patel, 2009 ) at an overall lower price (Scarfe et al., 2006 ).
The majority of clinicians consider CBCT images to be reliable and distortion free and are unaware of potential inaccuracies or inconsistencies that may exist when performing linear measurements or evaluating bone and anatomic structures prior to implant placement.

Many authors have reported bone measurements made on
CBCT images can be considered accurate, when errors less than 1 mm can be tolerated Torres et al., 2012 ;Wyatt & Pharoah, 1998 (Bartling, Freeman & Kraut, 1999 ;Buser & von Arx, 2000 ;Greenstein & Tarnow, 2006 ). Considering the inhomogeneity of data from our current review and the lack of conclusive evidence from clinical studies, we also recommend a safety margin of 2 mm from vital anatomical structures, when using 3D data from CBCT imaging .
It is possible that specific makes and models of CBCT equipment may have different levels of accuracy in linear measurements of the residual alveolar ridge. This could be potentially because of the many machine-specific, operator-independent variables such as filtration, target-object/object-sensor distances, reconstruction algorithms used, or different designs of head restraining devices that could potentially influence measurement accuracy. However, due to the inhomogeneity of the dependent variables identified (linear measurement indices) in this review, further attempts at identifying these machine-specific conditions for the purposes of comparison would not add to the outcomes of the present analysis as even the metric data from seemingly the same machine by two different investigators are not comparable.
In one study, the maxillary measurements were found to be less accurate than those of the mandible . This may be explained a potential reduction in overall density of the maxilla than the mandible due to the thinner cortical layer and greater cancellous component. On the other hand, Gerlach et al. ( 2013 ) found overestimation of mandibular dimensions on CBCT cross-sectional images, especially when assessing the cortical thickness .
This finding may result from errors introduced when measuring short distances on CBCT images with limited spatial resolution acquired at relatively large voxel dimensions (Molen, 2010 ) or to partial volume averaging, which appears when different bone densities appear in the same voxel (Barrett & Keat, 2004 ;Molen, 2010 ).
As expected, the majority of studies were in vitro-either on dry skulls or on cadaver samples-with only two clinical studies identified. Clinical studies are inherently difficult to perform as they require accurate, physical measurements of the bone intraoperatively.
Due to the nature of the ex vivo studies, a quality assessment of these investigations was not performed. Ex vivo studies are ranked low within the spectrum of strength of evidence within the hierarchical pyramid in a clinical setting (Hujoel, 2009  studies that had only one examiner Santana et al., 2012 ). Although calibration of the examiners is necessary for optimal diagnostic performance and reliability (de Oliveira et al. 2009) , only two authors reported that a measurement calibration procedure was performed, but without details Vasconcelos et al., 2015 ). The reported inter-and intra-examiner agreement was very high for all the studies.
There was a large heterogeneity of devices, parameters and software used in the included studies, which made a direct comparison impossible. Several studies reported that smaller voxel sizes did not lead to greater accuracy for the linear measurements at edentulous sites Luangchana et al., 2015 ;Torres et al., 2012 ;Waltrick et al., 2013 ) There appear to be no differences between software packages in measuring CBCT images . Nevertheless, clinicians should be cautious when using new software as there is little scientific, evidence-based validation of the performance of these algorithms.
Clinical extrapolation of the findings from ex vivo CBCT studies is inherently problematic as CBCT reconstruction algorithms are optimized for in vivo scanning of maxillofacial areas, which are composed of both skeletal and soft tissue elements. In addition, high-density materials such as root canal fillings, composite resins, metallic restorations, and dental implants create beam hardening artifacts (Schulze, Berndt & d ' Hoedt, 2010 ). Therefore, as most experimental conditions using dry skulls or formalin-fixed cadavers are not equivocal to clinical situations, the accuracy of linear measurements obtained ex vivo may not be directly comparable to in vivo situations and may result in over-or underestimation.
Soft tissues attenuate the X-ray beam, reducing tissue contrast increasing scatter and contributing to image noise, thus potentially affecting the accuracy of the relative measurements Gerlach et al., 2013 ;Patcas et al., 2012 ). Recent studies though have shown that accuracy outcomes were similar with and without soft tissues (Ganguly et al., 2011 ;Wood et al., 2013 ). Wood et al. ( 2013 ) showed that the presence of soft tissues had no effect when a 0.4 mm voxel size was used, and 0.2-mm scans demonstrated a clearly inferior accuracy associated with absence of soft tissues. Even though not directly comparable, all studies in the current review reported high accuracy outcomes for the linear measurements, irrespective of the presence or absence of soft tissues or soft tissue simulation, supporting the assertion that the presence of soft tissues in ex vivo CBCT studies is not a crucial factor for accuracy measurements. with great accuracy as confirmed by the small standard deviations . These authors attributed this finding to the use of methyl methacrylate as an embedding medium for the sections, which prevents shrinking artifacts (Wittenburg, Volkel, Mai & Lauer, 2009 ;Yang, Davies, Archer & Richards, 2003 ).
The two clinical studies included used ridge mapping for assessing the width of the edentulous alveolar ridge. Although it was not explicitly mentioned in these studies that this method is used as a control for the linear CBCT measurements, it was decided to include them in the present review as they fitted the presented inclusion and exclusion criteria. Despite the high agreement of the reported measurements in these studies, one should acknowledge certain limitations of this method such as the ability to accurately stop the measuring instruments at the first bone contact after penetrating the soft tissues, especially when the mucosa is mobile or the bone density is low, as well as to reproduce the point of entry precisely with the templates used for this purpose.
Finally, it must be mentioned that the current systematic review focused only on the accuracy of linear bone measurements on crosssectional and therefore multiplanar reformatted, two-dimensional CBCT images. However, CBCT imaging provides three-dimensional depiction of bony structures, making it a crucial diagnostic tool that, in addition to linear measurements, enables evaluation of the morphology, bone quality, and volume of the residual alveolar ridge, which are also important and basic considerations in overall implant site assessment.

| CONCLUSIONS
Based on the results of this systematic review, it can be concluded that: • CBCT provides cross-sectional images that demonstrate high accuracy and reliability for bony linear measurements on cross-sectional images related to implant treatment. Therefore, CBCT is an appropriate diagnostic tool for 3D preoperative planning.
• A wide range of error has been reported when performing linear measurements on CBCT images, with both over-and underestimation of dimensions in comparison with a gold standard.
Therefore, a 2 mm safety margin to adjacent anatomic structures should be considered when using CBCT.
• A voxel size of 0.3 to 0.4 mm is adequate to provide CBCT images of acceptable diagnostic quality for implant treatment planning.
• As most studies were ex vivo (i.e., dry skulls or cadavers), the reported results should be considered optimal. In clinical practice, measurement accuracy and reliability are most likely reduced as several factors (e.g., patient motion, device and software used, manual or automated procedures) might influence linear measurements on CBCT images.
• Due to the inhomogeneity of the extracted data from the included studies, it was not possible to conduct a meta-analysis to account for multivariate effect estimates. Thus, further studies that focus on determining which factors specifically influence the accuracy of the measurements in 3D imaging are recommended.