Application of cone beam volumetric tomography in endodontics.

In a 2008 article on cone beam volumetric tomography (CBVT) and dentoalveolar applications, Tyndall and Rathore wrote: "It is in the area of endodontic applications that the literature has proved most fruitful to date." This statement is even truer today than in 2008. A review of the literature has demonstrated that, in many cases, CBVT is more efficacious than traditional forms of 2-D imaging. Endodontic applications of CBVT include the diagnosis of periapical lesions due to pulpal inflammation, identification, and localization of internal and external resorption, the detection of vertical root fractures, the visualization of accessory canals, and elucidation of the causes of non-healing endodontically treated teeth. Prior to 2008, most published articles on CBVT applications in endodontics were either case reports or in vitro studies. Since that time more well designed clinically related scholarly activity has been published. This article attempts to survey the field of CBVT applications in endodontics and provide the readers with an overview of what has been found. The authors hope that this knowledge will form a foundation for appropriate clinical decision making with specific reference to selection criteria for the endodontic applications of CBVT.

Self-immolative Linkers in Prodrugs and Antibody Drug Conjugates in Cancer Treatment.

BACKGROUND: The design of anti-cancer therapies with high anti-tumour efficacy and reduced toxicity continues to be challenging. Anti-cancer prodrug and antibody-drug-conjugate (ADC) strategies that can specifically and efficiently deliver cytotoxic compounds to cancer cells have been used to overcome some of the challenges. The key to the success of many of these strategies is a self-immolative linker, which after activation can release the drug payload. Various types of triggerable self-immolative linkers are used in prodrugs and ADCs to improve their efficacy and safety. OBJECTIVE: Numerous patents have reported the significance of self-immolative linkers in prodrugs and ADCs in cancer treatment. Based on the recent patent literature, we summarise methods for designing the site-specific activation of non-toxic prodrugs and ADCs in order to improve selectivity for killing cancer cells. METHODS: In this review, an integrated view of the potential use of prodrugs and ADCs in cancer treatment are provided. This review presents recent patents and related publications over the past ten years uptill 2020. RESULTS: The recent patent literature has been summarised for a wide variety of self-immolative PABC linkers, which are cleaved by factors including responding to the difference between the extracellular and intracellular environments (pH, ROS, glutathione) through over-expressed enzymes (cathepsin, plasmin, ß-glucuronidase) or bioorthogonal activation. The mechanism for self-immolation involves the linker undergoing a 1,4- or 1,6-elimination (via electron cascade) or intramolecular cyclisation to release cytotoxic drug at the targeted site. CONCLUSION: This review provides the commonly used strategies from recent patent literature in the development of prodrugs based on targeted cancer therapy and antibody-drug conjugates, which show promise in therapeutic applications.

GAND classification and volumetric assessment of unilateral cleft lip and palate malformations using cone beam computed tomography.

The aim of this study was to propose a classification for unilateral cleft lip and palate (UCLP) malformations based on cone beam computed tomography (CBCT) images, as well as to estimate the amount of bone necessary for grafting, and to evaluate the relationship of this volume with scores obtained using the classification. CBCT images of 33 subjects with UCLP were evaluated according to gap, arch, nasal, and dental parameters (GAND classification). Additionally, these defects were segmented and the amount of graft needed for alveolar bone grafting was estimated. The reproducibility of GAND classification was analyzed by weighted kappa test. The association of volume assessment with the classification (gap and nasal parameters) was verified using analysis of variance, while the intra-observer agreement was analyzed using the intra-class correlation coefficient. The intra-observer reproducibility of the classification ranged from 0.29 to 0.92 and the inter-observer agreement ranged from 0.29 to 0.91. There were no statistically significant values when evaluating the association of the volume with the classification (P>0.05). The GAND classification is a novel system that allows the quick estimation of the extent and complexity of the cleft. It is not possible to estimate the amount of bone needed for alveolar bone grafting based on the classification; individualized surgical planning should be done for each patient specifically.

Fractal dimension analysis of weight-bearing bones of rats during skeletal unloading.

Fractal analysis was used to quantify changes in trabecular bone induced through the use of a rat tail-suspension model to simulate microgravity-induced osteopenia. Fractal dimensions were estimated from digitized radiographs obtained from tail-suspended and ambulatory rats. Fifty 4-month-old male Sprague-Dawley rats were divided into groups of 24 ambulatory (control) and 26 suspended (test) animals. Rats of both groups were killed after periods of 1, 4, and 8 weeks. Femurs and tibiae were removed and radiographed with standard intraoral films and digitized using a flatbed scanner. Square regions of interest were cropped at proximal, middle, and distal areas of each bone. Fractal dimensions were estimated from slopes of regression lines fitted to circularly averaged plots of log power vs. log spatial frequency. The results showed that the computed fractal dimensions were significantly greater for images of trabecular bones from tail-suspended groups than for ambulatory groups (p < 0.01) at 1 week. Periods between 1 and 4 weeks likewise yielded significantly different estimates (p < 0.05), consistent with an increase in bone loss. In the tibiae, the proximal regions of the suspended group produced significantly greater fractal dimensions than other regions (p < 0.05), which suggests they were more susceptible to unloading. The data are consistent with other studies demonstrating osteopenia in microgravity environments and the regional response to skeletal unloading. Thus, fractal analysis could be a useful technique to evaluate the structural changes of bone.

MRI effects on the teratogenicity of x-irradiation in the C57BL/6J mouse.

This investigation was undertaken in order to ascertain the combined effects of magnetic resonance imaging (MRI) fields and x-irradiation on the developing eye of the mouse strain C57B1/6J. Dams in groups of 15 were subjected to absorbed doses of 5, 15, and 30 cGy. Other dams (N = 15) were exposed to T2 spin-echo MRI fields under clinically realistic conditions following exposure to 30 cGy of x-irradiation. The developing eye was the biological end point studied. It was found that the 30-cGy dose resulted in teratogenic significance (p less than or equal to .05) for the C57B1/6J mouse. Groups exposed to both types of radiation fields demonstrated malformation levels similar to the 30-cGy irradiated animals with no additive or synergistic effects detected. The malformation rates and degree of statistical significance varied somewhat with unit of measurement, and analytical method. The results confirmed low level X-ray teratogenicity and suggested that the MRI techniques employed for this investigation did not enhance the teratogenicity of x-irradiation on eye malformations produced in the C57B1/6J mouse.

Digital subtraction radiography for detecting cortical and cancellous bone changes in the periapical region.

Previous studies have found that bony lesions cannot be visualized on conventional radiographs unless there is cortical plate involvement. The aim of this project was to compare the sensitivity of digital subtraction to conventional radiography for detecting periapical changes in cortical and cancellous bone. Using a long source-to-object X-ray technique and E-speed film, serial radiographs of a dry skull mandible were obtained. Two bone lesions per radiograph were simulated using #1 to 8 round burs. Conventional and digitally subtracted images were evaluated for lesion presence by a board of reviewers. The results demonstrated greater sensitivity scores for digitally subtracted images in identifying cortical and cancellous bone changes. The lower limit of detection was less for digitally subtracted images in cortical and cancellous bone as well.

Assessment of external root resorption using digital subtraction radiography.

Digital subtraction radiography was investigated for its capability to detect and quantify experimentally produced external root resorptive defects in teeth. Using a long source to object X-ray technique and E-speed film, serial radiographs of teeth with artificial lesions in a dry human skull (soft tissue simulated) were obtained. Receiver operating characteristic analysis was used to evaluate the diagnostic performance for each imaging system (conventional versus subtraction). To explore the quantitative assessment potential of digital subtraction radiography, images were produced after sequential demineralization by HCl. The acid solution was analyzed for calcium concentration by atomic absorption spectrophotometry. Three-dimensional histogram quantification for each subtracted image was performed. In overall performance for detecting experimentally produced external root resorption, digital subtraction radiography was found to be significantly superior to conventional radiography. In addition, digital subtraction radiography can provide quantification of experimentally produced external root resorptive defects.

Selection criteria for dental implant site imaging: a position paper of the American Academy of Oral and Maxillofacial radiology.

The American Academy of Oral and Maxillofacial Radiology (AAOMR) has reviewed the implant imaging literature and issues this position paper for preoperative assessment of the dental implant site. The history of dental implant radiology and basic imaging principles are reviewed. An overview is presented of anatomically salient features in the maxilla and mandible germane to implant imaging, specifically to cross-sectional or transverse imaging for endosseous implants. All current modalities, including intraoral, panoramic, cephalometric, tomographic, and computed tomography, are discussed in light of the imaging data needed to select optimum implant solutions. After reviewing the current literature, the AAOMR recommends that some form of cross-sectional imaging be used for implant cases and that conventional cross-sectional tomography be the method of choice for gaining this information for most patients receiving implants.

Detection of caries with conventional digital imaging and tuned aperture computed tomography using CRT monitor and laptop displays.

OBJECTIVE: The purpose of this study was to compare the diagnostic performance of conventional digital images and tuned aperture computed tomography (TACT) slices in caries detection through use of cathode-ray tube monitor and laptop displays. STUDY DESIGN: Forty-two extracted posterior teeth were mounted and imaged with a direct digital radiography system. Conventional digital bitewing projections and TACT slices were acquired. Images were viewed on a high-resolution cathode-ray tube monitor and on an active-matrix laptop display. Eight observers assessed caries status of occlusal and proximal surfaces of the teeth using all combinations of image and display modality. Observers' assessments were compared with the results of histologic examination of tooth sections. Possible differences in receiver operating characteristic curve areas among displays, image modalities, observers, and surfaces were analyzed by means of analysis of variance. RESULTS: There was no statistically significant difference between the diagnostic performances provided by the cathode-ray tube monitor and laptop displays in caries detection (P = .588). In addition, the performances of digital images and TACT slices were not significantly different (P = .843). CONCLUSIONS: Modern active-matrix laptop displays provide diagnostic quality for caries detection comparable to that obtainable with cathode-ray tube monitors.

Generation of TACT image slices using different reconstruction algorithms: effects on natural caries detection.

OBJECTIVE: The purpose of this study was to determine whether the method of reconstruction of tuned-aperture computed tomography (TACT) slices has an influence on observer performance in caries detection. STUDY DESIGN: Eight images of each of 40 extracted posterior teeth were acquired by using a solid state intraoral detector. Stacks of tuned-aperture computed tomography slices were generated by using the minimum and average reconstruction methods. Slices of the 2 experimental conditions were presented to 8 observers in a balanced order. Images were viewed on a high-resolution 21-in color monitor. Observers scored the presence/absence of caries by using a 5-point confidence scale. Observers' assessments were compared with histologic examinations of tooth sections. Receiver operating characteristic curves measured observers' diagnostic performance. Analysis of variance was used to test for possible significant differences between observers and between experimental conditions. Sensitivity, specificity, accuracy, and interobserver reliability were also calculated. RESULTS: No statistically significant differences between the 2 methods of reconstruction were found for the detection of either occlusal (P =.07) or proximal (P =.52) caries. Interobserver reliability was similar for both experimental conditions. CONCLUSIONS: The minimum and average methods of TACT reconstruction provide comparable performances for caries detection tasks.

Effect of angular disparity of basis images and projection geometry on caries detection using tuned-aperture computed tomography.

OBJECTIVE: The purpose of this study was to determine whether projection geometry and angular disparity of basis images used for tuned-aperture computed tomography (TACT) slice generation influence observer performance in caries detection. STUDY DESIGN: Four sets of 8 projections of each of 40 teeth were acquired by using a digital sensor. Each set was radially distributed and subtended angular disparities of 10 degrees, 20 degrees, 30 degrees, and 40 degrees, representing strict projection geometries. A fifth set of images was acquired by using unconstrained geometry. TACT slices were generated from all experimental conditions and presented to 8 observers who viewed the images on a high-resolution monitor. Observers scored the presence/absence of caries with a 5-point confidence scale. Ground truth was achieved by histologic examination of tooth sections. Receiver operating characteristic curves measured observers' diagnostic performance. Analysis of variance was used to test for significant differences among observers and between experimental conditions. RESULTS: No statistically significant difference between angular disparities was found for the detection of either occlusal (P =.105) or proximal (P =.052) caries. No statistically significant difference between unconstrained and stringent projection geometries was found for the detection of either occlusal (P =.879) or proximal (P =.130) caries. CONCLUSIONS: Angular disparities ranging from 10 degrees to 40 degrees provide comparable performance in caries detection with TACT. Both unconstrained and stringent projection geometries may be used when reconstructing TACT slices for caries detection tasks.

Temporomandibular joint imaging: a comparative study of diagnostic accuracy for the detection of bone change with biplanar multidirectional tomography and panoramic images.

This in vitro investigation compares biplanar (sagittal and coronal) temporomandibular joint images produced by multidirectional tomographic and panoramic techniques for diagnostic accuracy in the detection of simulated degenerative lesions. A series of dentin chips placed at four locations on the head of a temporomandibular joint condyle in a dried human skull were imaged with tomographic and panoramic modalities. Equal numbers of images with and without chips were scored by four examiners with the use of confidence levels for presence or absence of the lesion. To assess intra-examiner reliability, each examiner viewed one of the modalities twice. Responses were assessed by generating receiver operating characteristic curves and analyzing the area (A(z)) under the curves with analysis of variation methods. Biplanar tomography provided significantly more accurate assessment of condylar lesions than biplanar panoramic images (p = 0.007). No statistical difference by location (p = 0.592) was found. The effects of observer and repeated observation were marginally significant at p = 0.046 and p = 0.030, respectively.

A comparison of Kodak Ektaspeed Plus film and the Siemens Sidexis digital imaging system for caries detection using receiver operating characteristic analysis.

OBJECTIVE: To evaluate the accuracy of proximal caries detection comparing enhanced and unenhanced Siemens Sidexis CCD-based digital images with Ektaspeed Plus films utilizing receiver operating characteristic analysis. STUDY DESIGN: Sixty extracted teeth (24 posterior and 36 anterior) were imaged under identical standardized geometric and exposure conditions. Six observers, using a 5-point confidence scale, rated 120 proximal surfaces for the presence or absence of carious lesions by means of three image modalities: (1) observer enhanced and (2) unenhanced Sidexis displays, and (3) Ektaspeed Plus films. The ground truth was determined by microscopic analysis of ground sections. Receiver operating characteristic curves were generated with calculated areas (AZ) analyzed with analysis of variance for effect of reader, reading, and modality. RESULTS: Analysis of variance demonstrated significant differences among readers, readings and modalities (mean square values of 0.012, 0.005, 0.004, F ratios of 13.604, 5.329, 5.100; p = values of 0.001, 0.043, and 0.030, respectively). Post-hoc paired comparisons of modalities using Tukey's statistic demonstrated that only film and enhanced Sidexis images were different from each other (p = 0.024). AZ scores were 0.7650, 0.7499, and 0.8008 respectively, for unenhanced Sidexis, enhanced Sidexis, and Ektaspeed Plus film. CONCLUSION: Unenhanced digital Sidexis images were equivalent to film for the detection of proximal caries in this in vitro study. Observer enhanced Sidexis images exhibited a statistically significant lower diagnostic accuracy than the unenhanced digital and film images.

Comparison of film, direct digital, and tuned-aperture computed tomography images to identify the location of crestal defects around endosseous titanium implants.

This study compared diagnostic performance obtained from two-dimensional and three-dimensional x-ray images. The latter were produced with a new tomosynthetic method based on aperture theory called tuned-aperture computed tomography. Seven human cadaver mandibular segments containing a total of 20 endosseous implants with a small randomly positioned alveolar crestal defect at each implant site were imaged in two dimensions with periapical film and with a charge-coupled digital detector, and digitally with the same detector in three dimensions with tuned-aperture computed tomography and subtracted tuned-aperture computed tomography techniques. Seven trained dentists viewed randomized displays of all modalities. Outcomes of the diagnostic task of identifying the locations of crestal defects were quantified with accuracy, confidence, and time performance measures. Analyses of variance demonstrated that differences between either three-dimensional technique and either two-dimensional modality were significant for all measures (p < 0.001). These findings suggest that clinically applied TACT methods hold promise as an improvement over the status quo.

Periodontitis detection efficacy of film and digital images.

OBJECTIVE: The objective of this study was to evaluate the accuracy of alveolar crestal bone detection in a comparison of unenhanced and enhanced Sidexis (Siemens Medical Systems, Inc., Bensheim, Germany) digital images with Ektaspeed Plus (Eastman Kodak, Rochester, N.Y.) films by means of receiver operating characteristic analysis. STUDY DESIGN: More than 100 proximal and furcal areas in the anterior and posterior areas of the mandible and maxilla of each of three tissue-equivalent human skull phantoms were imaged with film, direct digital images, and contrast- and brightness-enhanced digital images. Alveolar crest status was assessed by a consensus panel of three experts who used the Delphi method and evaluated information from all of the imaging modalities concurrently. Five observers assessed all images for the presence or absence of crestal bone loss using a five-point confidence scale. Receiver operating characteristic curves were generated, and calculated areas (Az) were analyzed by means of analysis of variance. RESULTS: The expert panel determined that of 106 crestal areas, 48 were disease free and 58 exhibited bone loss greater than 2 mm apical to the cemento-enamel junction. Analysis of variance of observer Az scores showed significant differences among readers (p < 0.001) and among readings (p = 0.027), but not among modalities (p = 0.435). Mean Az values for the different modalities were as follows: Sidexis, 0.70; enhanced Sidexis, 0.71; Ektaspeed Plus films, 0.735. CONCLUSION: The Sidexis digital imaging system was not significantly different from Ektaspeed Plus film for crestal bone evaluation in this in vitro study.

TACT imaging of primary caries.

OBJECTIVE: Tuned-aperture computed tomography, a new method for creating 3-D radiographic information based on optical aperture theory, was evaluated for diagnostic efficacy in primary caries detection. STUDY DESIGN: Sixty-four extracted teeth with 89 carious lesions were imaged with D-speed film, direct digital, and TACT modalities. A commercially available, 8-bit, charge-coupled device was used in the later two modalities. Six trained observers were asked to identify the presence or absence and depth of interproximal and occlusal lesions for all three modalities. The teeth were sectioned and examined microscopically to determine ground truth. Logistic regression analysis was performed for all three imaging systems for the detection task. Analysis of variance was used for depth determination. Detection of lesion, depth of lesion accuracy, and time for diagnosis were also examined. RESULTS: For caries detection TACT and film were not different (p = 0.2216) with the Wald statistic. Film and TACT were significantly more accurate than the digital system (p = 0.0001). Scheffe's post hoc test revealed that TACT and film were more accurate than the direct digital system for determining lesion depth (p = 0.05) but not statistically different when compared with each other. The detection data were substantiated further by receiver operating characteristic analysis that demonstrated similar statistical relationships. Time required per diagnosis was not shown to be statistically different among the three imaging modalities. CONCLUSIONS: We conclude for caries detection and depth determination that TACT could not be distinguished from film despite the significant relative loss of information capacity in the charge-coupled device receptor. The relatively poorer performance yielded by the digital control images suggests that increased information capacity associated with more modern charge-coupled device detectors may improve diagnostic performance for both direct digital and TACT displays over that demonstrated in this investigation.

Accuracy of mandibular cross-sectional imaging with tuned- aperture computed tomography (TACT), iteratively reconstructed TACT, and multidirectional, linear, and transverse panoramic tomography.

OBJECTIVE: This study was designed to compare 5 modalities with respect to accuracy in mandibular cross-sectional imaging. The modalities tested were tuned-aperture computed tomography (TACT), iteratively reconstructed TACT, multidirectional tomography, linear tomography, and transverse panoramic tomography. STUDY DESIGN: Twenty sites were selected from 3 dry human mandibles, and cross-sectional views were imaged through use of each of the 5 modalities. A quantitative analysis included measurements of 2 linear distances; a qualitative study included image evaluation by 6 observers. A nested mixed analysis of variance model was used to control for mandibles and locations within mandibles for the quantitative analysis; the Cochran-Mantel-Haenszel test was used for the qualitative analysis. RESULTS: There was a significant difference in measurement error for maximum height but not for width. There was also a significant difference in qualitative image evaluation results. CONCLUSIONS: Of the 5 modalities tested, the narrow-layer multidirectional tomographic technique produced the greatest diagnostic accuracy and quality in cross-sectional imaging. The transverse panoramic tomographic technique produced the least diagnostic accuracy and quality. Linear tomography, TACT, and iteratively reconstructed TACT were intermediate in accuracy and quality.

Video-based teleradiology for intraosseous lesions. A receiver operating characteristic analysis.

Immediate access to off-site expert diagnostic consultants regarding unusual radiographic findings or radiographic quality assurance issues could be a current problem for private dental practitioners. Teleradiology, a system for transmitting radiographic images, offers a potential solution to this problem. Although much research has been done to evaluate feasibility and utilization of teleradiology systems in medical imaging, little research on dental applications has been performed. In this investigation 47 panoramic films with an equal distribution of images with intraosseous jaw lesions and no disease were viewed by a panel of observers with teleradiology and conventional viewing methods. The teleradiology system consisted of an analog video-based system simulating remote radiographic consultation between a general dentist and a dental imaging specialist. Conventional viewing consisted of traditional viewbox methods. Observers were asked to identify the presence or absence of 24 intraosseous lesions and to determine their locations. No statistically significant differences in modalities or observers were identified between methods at the 0.05 level. The results indicate that viewing intraosseous lesions of video-based panoramic images is equal to conventional light box viewing.

Dental anomalies associated with amelogenesis imperfecta: a radiographic assessment.

Amelogenesis imperfecta, a group of hereditary conditions primarily affecting the enamel, has been associated with dental anomalies, including taurodontism, congenitally missing teeth, delayed eruption, crown resorption, and abnormal enamel density. The purpose of this study was to assess the prevalence of these anomalies in an amelogenesis imperfecta population. The study group consisted of members of 9 unrelated families--22 family members with amelogenesis imperfecta and 13 unaffected family members. Panoramic radiographs were evaluated for taurodontism, congenitally missing teeth, delayed tooth eruption, pathologic dental resorption, pulp calcification, and radiographic enamel density. The prevalence of taurodontism was similar in people with amelogenesis imperfecta and normal people; all of the remaining parameters were more commonly observed in people with amelogenesis imperfecta. The radiographic enamel density was quantitatively reduced in teeth affected by amelogenesis imperfecta in comparison with teeth with normal enamel. These findings suggest that some of the features associated with amelogenesis imperfecta result from abnormal enamel formation (eg, decreased enamel density, crown resorption) whereas others may occur as a result of expression of the genetic mutation in cells other than ameloblasts (eg, abnormal eruption, pulp calcification).

The effect of rare earth filtration on patient exposure, dose reduction, and image quality in oral panoramic radiology.

Rare earth intensifying screen material (Gd2O2S:Tb) was added to the standard Al filtration of an oral panoramic x-ray unit, resulting in a beam capable of achieving reductions in patient dose without a loss of image quality. The added rare earth filtration technique resulted in patient dose reductions of 21-56%, depending on anatomic sites, when compared to the conventional Al filtration technique. Films generated from both techniques were measured densitometrically and evaluated by a panel of practicing clinicians. Diagnostically significant differences were minimal. The results indicate that use of rare earth filters in oral panoramic radiography is an effective means of reducing exposures of dental patients to ionizing radiation.