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.

Advanced fluorescence lifetime imaging algorithms for CMOS single-photon sensor based multi-focal multi-photon microscopy.

We have developed a fast hardware friendly bi-exponential fluorescence lifetime algorithm suitable for 2D CMOS single-photon avalanche diode (SPAD) arrays. The performance of the proposed algorithm against other techniques is demonstrated on the data from a plant specimen (Convallaria) by using 0.13µm CMOS SPAD arrays mounted on a multi-beam multi-photon microscopy system.

Note: multi-confocal fluorescence correlation spectroscopy in living cells using a complementary metal oxide semiconductor-single photon avalanche diode array.

Living cells are heterogeneous and rapidly changing biological samples. It is thus desirable to measure molecular concentration and dynamics in many locations at the same time. In this note, we present a multi-confocal setup capable of performing simultaneous fluorescence correlation spectroscopy measurements, by focusing the spots with a spatial light modulator and acquiring data with a monolithic 32 × 32 single-photon avalanche photodiode array. A post-processing method is proposed to correct cross-talk effects between neighboring spots. We demonstrate the applicability of our system by simultaneously measuring the diffusion of free enhanced Green Fluorescent Protein (eGFP) molecules at nine different points in living cells.

Correlating cone beam CT results with temporomandibular joint pain of osteoarthritic origin.

OBJECTIVES: The purpose of this study was to determine whether bony changes in temporomandibular joint (TMJ) osteoarthritis (OA) is correlated with pain and other clinical signs and symptoms. METHODS: Clinical data and cone beam CT (CBCT) images of 30 patients with TMJ OA were analysed. The criteria of Koyama et al (Koyama J, Nishiyama H, Hayashi T. Follow-up study of condylar bony changes using helical computed tomography in patients with temporomandibular disorder. Dentomaxillofac Radiol 2007; 36: 472-477.) and Ahmad et al [Ahmad M, Hollender L, Anderson Q, Kartha K, Ohrbach R, Truelove EL, et al. Research diagnostic criteria for temporomandibular disorders (RDC/TMD): development of image analysis criteria and examiner reliability for image analysis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 107: 844-860.] were used to classify the condyles observed on the CBCT. Clinical measures included self-reported pain, mandibular range of motion, TMJ sound, pain on palpation of the TMJ and masticatory muscles, and pain on jaw function. Generalized linear modelling was used to correlate the clinical and radiographic findings and Spearman's rho was used to correlate the two classification systems. RESULTS: There was poor correlation between the maximum condyle change and pain rating (Koyama: r² = 0.1443, p = 0.3995; Ahmad: r² = 0.0273, p = 0.9490), maximum mouth opening (Koyama: r² = 0.2910, p = 0.0629; Ahmad: r² = 0.2626, p = 0.0951), protrusion (Koyama: r² = 0.0875, p = 0.7001; Ahmad: r² = 0.1658, p = 0.3612), right lateral motion (Koyama: r² = 0.0394, p = 0.9093; Ahmad: r² = 0.0866, p = 0.6877) and left lateral motion (Koyama: r² = 0.0943, p = 0.6494; Ahmad: r² = 0.1704, p = 0.3236). Strong correlation was observed between Koyama et al's and Ahmad et al's classifications for average (r = 0.9216, p < 0.001) and maximum (r = 0.7694; p < 0.0001) bony change. CONCLUSIONS: There was poor correlation between condylar changes (as observed on CBCT images), pain and other clinical signs and symptoms in TMJ OA.

Ex vivo comparison of Galileos cone beam CT and intraoral radiographs in detecting occlusal caries.

OBJECTIVE: The aim of this study was to compare the accuracy of cone beam CT (CBCT) with intraoral radiographs for detection of occlusal caries. METHODS: A set of 60 extracted teeth were imaged using a Sirona Galileos CBCT system (Sirona Dental Systems, Bensheim, Germany) and an intraoral Planmeca® system (Planmeca OY, Helsinki, Finland). Six observers looked at both modalities and used a five-point confidence scale to evaluate presence or absence of occlusal caries. Histology was used as the gold standard. Receiver operating characteristic analysis and weighted kappa statistics were used for statistical analysis. Differences in the area under the curve (AUC) values between observers and modalities were analysed using analysis of variance (ANOVA). Differences in sensitivity and specificity were analysed using the Wilcoxon test. Interobserver and intraobserver reliability was assessed by weighted kappa scores. RESULTS: The mean value and standard deviation of AUC was 0.719 ± 0.038 for CBCT and 0.649 ± 0.062 for the intraoral radiographs. The ANOVA results demonstrated that there was no significant difference between the modalities and the observers. The interobserver kappa for pairs of observers ranged from fair to substantial for bitewings (0.244-0.543) and CBCT (0.152-0.401). Four out of six observers reported higher sensitivity but lower specificity with CBCT. The Wilcoxon exact p-value showed no difference in sensitivity (0.175) or specificity (0.573) between the two modalities. CONCLUSION: Based on the results we conclude that the Sirona CBCT unit cannot be used for the sole purpose of looking at occlusal caries.

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.

Effect of the number of basis images on the detection of longitudinal tooth fractures using local computed tomography.

OBJECTIVES: To determine the effect of the number of basis images on the accuracy of local CT (LCT) in detecting longitudinal fractures and test the accuracy of terminal point assessment. METHODS: Longitudinal fractures were induced in 30 of 60 posterior teeth. LCT volumes were generated from 180, 60, 36 and 20 basis images. Ten observers determined the presence of a fracture and its terminal point. Receiver operating characteristic (ROC) analysis was used to quantify detection accuracy, and kappa statistics were used to quantify the concordance between actual and observed terminal point locations. RESULTS: A(z)-values were 0.91, 0.84, 0.74, 0.57 and 0.70 for LCT180, LCT60, LCT36, LCT20 and conventional radiography, respectively (ANOVA: P<0.0001). LCT180 and LCT60 outperformed the other modalities. The respective kappa values for terminal point assessment were 0.52, 0.40, 0.37, 0.16 and 0.32 (ANOVA: P=0.00). LCT180 and LCT60 provided better agreement. CONCLUSIONS: LCT maintained its efficacy for detecting longitudinal fractures with 60 instead of 180 basis images. Agreement between actual and observed terminal point locations was moderate for LCT60 and LCT180.

Minimum number of basis projections for caries detection with local CT.

OBJECTIVES: To investigate the relationship between the number of basis projections for local computed tomography (CT) and the detection of proximal caries and to find a minimum number of projections needed to maintain diagnostic accuracy. METHODS: We presented observers (n = 12) with stacks of both axial and vertical CT slices of 23 extracted teeth placed in a dry human mandible. The slices were prepared with 14, 20, 33 and 100 basis projections. The observers scored the proximal surfaces for the presence of caries on a 1-5 confidence scale. The performance of the varying number of projections was compared with conventional digital radiographs. RESULTS: The performance of all four CT modalities was significantly better than conventional radiographs (P = 0.005 to P = 0.021) and showed a consistent increase with the number of projections. Diagnostic performance depended significantly on lesion depth (P = 0.00), but not on observer. CONCLUSIONS: We conclude that the number of CT projections used can be reduced at least to 20 with the diagnostic performance still markedly better than that of conventional film, provided that the observer can make use of both axial and vertical stacks of CT slices.

Detection of caries with local CT.

OBJECTIVES: An in vitro observer study of the detection of interproximal caries by local CT. METHODS: Detection of caries by means of conventional two-dimensional (2D) digital radiography and by two CT modalities was compared. Ground truth was obtained from histological examination of the sectioned teeth. Twenty-three extracted teeth (46 surfaces) were placed in groups of six in two dry mandibles. The observers (n=10) scored the proximal surfaces for the presence of caries on a 1-5 confidence scale. Data analysis used analysis of variance (a General Linear Model). Observer and method were entered into the model as within-subject variables and lesion depth was entered as a between-subjects variable. RESULTS: The analysis showed observer, method and lesion depth effects as well as several interaction effects to be significant. Observers performed significantly better with the vertically reformatted CT slices than with conventional radiographs (P=0.025). Furthermore, there were significant differences between observers, and several interactions were found to be significant. This means that although the reformatted slices performed best overall, this performance differed significantly depending on observer and on lesion depth. CONCLUSIONS: Vertically reformatted CT slices obtained with local CT performed significantly better than conventional 2D digital radiographs in visually detecting caries. Axial slices did not perform better than conventional radiographs. When vertically reformatted slices are used, local CT is a promising tool for the detection of interproximal caries.

Effect of data compression on proximal caries detection: observer performance with DenOptix photostimulable phosphor images.

OBJECTIVES: To study the effect of lossy image compression on caries detection. Null hypothesis states no difference in caries detection efficacy among observers using original digital images versus images compressed at various rates of compression. METHODS: Digital images of 41 extracted posterior teeth were obtained with a storage phosphor DenOptix (Gendex DenOptix Imaging system) system. Images were exported in Tagged Image File Format (TIFF) and compressed with Joint Photographic Experts Group File Interchange Format (JFIF), as provided by the software of the imaging system. The compressions options JFIF100%, JFIF75% and JFIF50% resulted in reducing the image size to 1:2, 1:11 and 1:16, respectively. Eight observers evaluated the presence or absence of caries on a 5-point confidence scale. The actual caries status of each proximal surface was determined by ground section histology. Responses were evaluated by receiver operating characteristic (ROC) analysis. Areas under the curves (Az) were assessed using analysis of variance (ANOVA). RESULTS: The mean Az scores were 0.85 for original/uncompressed images, and 0.89 for JFIF100%, 0.88 for JFIF75% and 0.88 for JFIF50% images. These differences were not statistically significant (P = 0.26). Differences between observers were also not statistically significant (P = 0.12). CONCLUSIONS: JFIF compression at the level of 1:16 can be used without significant deterioration in diagnostic accuracy for proximal caries detection.

Influence of the number of basis images and projection array on caries detection using tuned aperture computed tomography (TACT).

OBJECTIVES: to determine if the number of basis images and spatial distribution of the projection array used for TACT slice generation influence observer performance in caries detection. METHODS: In the first experiment, 2, 4, 8 and 12 basis projections of each of 40 teeth were acquired using a CMOS digital radiography sensor. Projections were distributed radially in space using a 20 degree angular disparity. TACT slices were generated from the four subgroups of images, presented to eight observers, and viewed on a high-resolution monitor. Observers scored the presence/absence of caries using a 5-point confidence scale. Gold standard was histological examination of tooth sections. ROC curves measured observer diagnostic performance. ANOVA tested for significant differences between observers and experimental conditions. In the second experiment, the number of basis projections judged to be satisfactory for TACT slice generation was used. Horizontal and vertical linear arrays of projections were compared to the circular projection array. RESULTS: There was a statistically significant difference between the numbers of basis projections in the detection of both occlusal (P=0.006) and proximal caries (P=0.005). No significant difference was found between projection arrays in the detection of either occlusal (P=0.065) or proximal (P=0.515) caries. CONCLUSIONS: The number of TACT basis projections significantly influences caries detection. Eight or more images should be used. Either linear-vertical, linear-horizontal or circular arrays of basis projections may be used for TACT slice generation in caries detection tasks.

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.

Evaluation of tuned aperture computed tomography (TACT) in the localization of simulated periodontal defects.

OBJECTIVES: To compare the diagnostic efficacy of tuned aperture computed tomography (TACT) with the application of the 'buccal object rule' (BOR) in the localization of simulated periodontal defects. METHODS: Thirty interproximal sites were selected in fifteen cadaver segments of maxillae and mandible. Artificial periodontal defects were created using round burs and 40% formic acid in the buccal, lingual or mid-buccolingual areas. Eight basis projections were obtained and TACT slices were reconstructed for each region of interest. Two of the basis images were used in application of BOR for localization of the defect. Eight observers scored the location of defects using TACT slices and the paired radiographs separately. Data were analysed using the kappa statistic and ANOVA. RESULTS: A mean weighted kappa of 0.14 for localization was obtained with both BOR and TACT. Using ANOVA, there was no significant difference between modality and observer. There was however, a significant difference (P=0.019) between different defect sizes. Both modalities performed better with larger defect sizes. TACT performed slightly better than BOR when the smaller lesions were included; however, with larger lesions, this trend was reversed. CONCLUSIONS: The results confirm the relationship between correlation distance (the resultant slice width) and object size in the application of TACT for localization. BOR remains a simple yet effective tool for localization. The clinical significance is not clear considering the low kappa scores obtained with both the modalities.

The effect of the number of iterative restorations on tuned aperture computed tomography for approximal caries detection.

OBJECTIVES: To determine whether the number of iterative restorations performed on TACT images affects observers' ability to detect dental caries. METHODS: Eight TACT basis images of 40 extracted human posterior teeth were acquired using a CCD sensor. TACT slices of each tooth were generated and subsequently submitted to 1, 2 or 3 iterative restorations. Stacks of images from the three experimental conditions were presented to six observers in a balanced order, on a high-resolution 21' color monitor. Observers scored the presence or absence of approximal caries using a 5-point confidence scale. Observers' assessments were compared with the results of histological examination. Receiver operating characteristic (ROC) curves were generated and possible significant differences between observers and between modalities tested by ANOVA. The level of significance was set at alpha=0.05. Interobserver reliability was calculated as intraclass correlation. RESULTS: Mean areas under the ROC curves (A(z)) for the three experimental conditions were 0.791 (one iterative restoration), 0.81 (two iterative restorations), and 0.778 (three iterative restorations). ANOVA did not demonstrate any significant difference between modalities (P=0.25) but did so between observers (P=0.031). Interobserver reliability was similar for all experimental conditions tested. CONCLUSIONS: Varying the number of iterative restorations from one to three does not affect observers' ability to detect approximal caries with TACT slices.

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.

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.

Comparison between PAI and quantitative digital radiographic assessment of apical healing after endodontic treatment.

OBJECTIVE: The purpose of this study was to compare both subjective (Periapical Index, PAI) and objective (densitometric) radiographic evaluation of healing after endodontic treatment for apical periodontitis. STUDY DESIGN: Standardized radiographs of 103 teeth taken at baseline (immediately after endodontic treatment) and at 1, 4, 12, 26, and 52 weeks were evaluated. Consensus PAI scores obtained from 7 calibrated observers served as "true scores." Densitometric estimates of periapical status were obtained from digitized radiographs as the ratio of mean gray value of an area of radiolucency (AR) to an adjacent and similar-sized normal (N) area (AR/N). The selected regions of interest on baseline images were automatically superimposed on postoperative images. All estimates of change were measured with respect to baseline. The subtraction estimate was expressed as AR(S)-N(S). Linear regression was used to analyze longitudinal changes against baseline and to assess the relationship of PAI and AR/N and of change in PAI with respect to baseline and AR(S)-N(S). RESULTS: Five hundred fifty-six PAI scores were generated, with 547 AR/N values and 444 subtraction estimates. PAI, AR/N, and AR(S)-N(S) demonstrated statistical significance for change (P < or = .05) starting at 12 weeks. PAI was significantly correlated with AR/N (P < .0001), as was CHPAI with AR(S)-N(S) (P < .024). CONCLUSION: The PAI and 2 densitometric estimates (AR/N and AR(S)-N(S)) detected healing of apical periodontitis at 12 weeks after treatment. No difference could be observed among the methods.

Analysis of fractal dimensions of rat bones from film and digital images.

OBJECTIVES: (1) To compare the effect of two different intra-oral image receptors on estimates of fractal dimension; and (2) to determine the variations in fractal dimensions between the femur, tibia and humerus of the rat and between their proximal, middle and distal regions. METHODS: The left femur, tibia and humerus from 24 4-6-month-old Sprague-Dawley rats were radiographed using intra-oral film and a charge-coupled device (CCD). Films were digitized at a pixel density comparable to the CCD using a flat-bed scanner. Square regions of interest were selected from proximal, middle, and distal regions of each bone. Fractal dimensions were estimated from the slope of regression lines fitted to plots of log power against log spatial frequency. RESULTS: The fractal dimensions estimates from digitized films were significantly greater than those produced from the CCD (P=0.0008). Estimated fractal dimensions of three types of bone were not significantly different (P=0.0544); however, the three regions of bones were significantly different (P=0.0239). The fractal dimensions estimated from radiographs of the proximal and distal regions of the bones were lower than comparable estimates obtained from the middle region. CONCLUSIONS: Different types of image receptors significantly affect estimates of fractal dimension. There was no difference in the fractal dimensions of the different bones but the three regions differed significantly.

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.