BASIC RESEARCH – TECHNOLOGY

Frank C. Setzer, DMD, PhD,

Artificial Intelligence for the MS,* Katherine J. Shi, DMD,†
Zhiyang Zhang, BS,‡ Hao Yan,
Computer-aided Detection of PhD,‡ Hyunsoo Yoon, PhD,‡
Mel Mupparapu, DMD, MDS,
Periapical Lesions in Cone- DipABOMR,x and Jing Li, PhD‡

beam Computed Tomographic

Images

ABSTRACT
SIGNIFICANCE
Introduction: The aim of this study was to use a Deep Learning (DL) algorithm for the
automated segmentation of cone-beam computed tomographic (CBCT) images and the Artificial intelligence has been
detection of periapical lesions. Methods: Limited field of view CBCT volumes (n 5 20) widely used in biomedical
containing 61 roots with and without lesions were segmented clinician dependent versus using image analysis in other medical
the DL approach based on a U-Net architecture. Segmentation labeled each voxel as 1 of 5 fields. The application of Deep
categories: “lesion” (periapical lesion), “tooth structure,” “bone,” “restorative materials,” and Learning algorithms to identify
“background.” Repeated splits of all images into a training set and a validation set based on 5- periapical lesions in CBCT
fold cross validation were performed using Deep Learning segmentation (DLS), and the results volumes may enhance
were averaged. DLS versus clinical-dependent segmentation was assessed by dichotomized dentists’ diagnostic efforts.
lesion detection accuracy evaluating sensitivity, specificity, positive predictive value, negative
predictive value, and voxel-matching accuracy using the DICE index for each of the 5 labels.
Results: DLS lesion detection accuracy was 0.93 with specificity of 0.88, positive predictive
value of 0.87, and negative predictive value of 0.93. The overall cumulative DICE indexes for the
individual labels were lesion 5 0.52, tooth structure 5 0.74, bone 5 0.78, restorative materials
5 0.58, and background 5 0.95. The cumulative DICE index for all actual true lesions was
0.67. Conclusions: This DL algorithm trained in a limited CBCT environment showed
excellent results in lesion detection accuracy. Overall voxel-matching accuracy may be
benefited by enhanced versions of artificial intelligence. (J Endod 2020;-:1–7.)

KEY WORDS
Artificial intelligence; cone-beam computed tomography; Deep Learning; digital imaging/
radiology; periapical lesion; U-Net

Apical periodontitis is the primary disease in endodontics, comprising about 75% of radiolucent jaw From the Departments of *Endodontics
and xOral Medicine, School of Dental
lesions1. It is highly prevalent, affecting 33%–62% of the population in age groups ranging from 20 to .60 Medicine, University of Pennsylvania,
years2. The principal diagnostic tool for the detection of apical periodontitis is intraoral dental radiography Philadelphia, Pennsylvania; †Private
by means of detecting periapical lesions (PLs). This is associated with several challenges and limitations. Practice, University of Pennsylvania,
Traditional 2-dimensional (2D) radiographs depict a summation of all content in the X-ray pathway and its Philadelphia, Pennsylvania; and ‡School
of Computing, Informatics, and Decision
attenuation within the structures. This content-rich environment of the oral cavity and jaws, including
Systems Engineering, Arizona State
different structures, tissues, and restorative materials, greatly increases the chance that lesions, University, Tempe, Arizona
particularly during early stages, will be masked3. Moreover, detection and a differential diagnosis rely on
Address requests for reprints to Dr Frank
observer interpretation, which is known to be inconsistent4,5. C. Setzer, School of Dental Medicine,
Three-dimensional (3D) imaging technology in the form of cone-beam computed tomographic University of Pennsylvania, 240 S 40th
(CBCT) imaging is now common in clinical practice with approximately 80% utilization among Street, Philadelphia, PA 19104.
endodontists for diagnosis and treatment planning6. Compared with 2D periapical radiography, CBCT E-mail address: fsetzer@upenn.edu
0099-2399/$ - see front matter
imaging has increased the accuracy of detecting periapical lesions. A meta-analysis reported a pooled
sensitivity and specificity of 0.70 and 0.78 for digital radiography compared with 0.95 and 0.88 for CBCT Copyright © 2020 American Association
of Endodontists.
imaging, respectively7. However, in clinically relevant situations, such as smaller lesions on root-filled
https://doi.org/10.1016/
teeth, CBCT accuracy is greatly reduced (sensitivity 5 0.63, specificity 5 0.69)8. Moreover, clinician- j.joen.2020.03.025

JOE  Volume -, Number -, - 2020 Artificial Intelligence for Detecting Periapical Lesions 1
dependent interpretation of CBCT imaging still
suffers from low inter- and intraobserver
agreement. An observer consensus range of
only 0.32–0.49 for PLs was reported9.
Computer-aided detection and
diagnosis (CAD) has been widely applied to
biomedical image analysis outside of dentistry.
CAD systems are computer applications that
assist in the detection and/or diagnosis of
diseases by providing an unbiased “second
opinion” to the image interpreter10, aiming at
improving accuracy and reducing time for
analysis11. Computer-aided detection (CADe)
systems identify the presence and location of
lesions in biomedical images. Computer-aided
diagnosis (CADx) systems characterize lesions
(eg, they distinguish between benign and
malignant tumors). With the rapid growth of
Deep Learning (DL) algorithms in image-based
applications, CAD systems can now be trained
by DL to provide more advanced capability (ie,
the capability of artificial intelligence [AI]) to best
assist clinicians.
Few studies investigated CAD systems
in dentistry. DL/AI-based CAD systems are
rare. Existing applications are still insufficient in
improving the objectivity and accuracy of
lesion detection and diagnosis because of
several limitations. The majority of algorithms
are semiautomated and thus require a user
selection of seed points followed by manual
adjustments. The accuracy of these algorithms
relies heavily on user experience. Automated
algorithms based on thresholding12–14, region
growing15–17, and statistical methods18,19
have been published but have not reached
clinical practice. Most algorithms are based on
2D single slices of CBCT volumes or
panoramic radiographs, which provide only a
singular view12–19. Because of this deficiency,
some lesions may be obscured and missed. In
addition, radiographic characteristics of
lesions may not fully present, causing
difficulties for attempts at differential
diagnosis17.
Our short-term goals for the present
study was to develop and validate a DL
platform that segments “lesion” (PL), “tooth
structure,” “bone,” “restorative materials,” and
“background” (5 labels) on CBCT images and
to compare its lesion detection accuracy to
that of experienced clinicians. Our long-term
goal is to develop an advanced CADe/CADx
platform empowered by AI to automate the
segmentation of whole CBCT volumes, detect
lesions with high accuracy and efficiency, and
ultimately differentiate different types of oral
pathoses with high-precision AIDen (Artificial
Intelligence in Dentistry). The segmentation
algorithm developed for this study
automatically leads to the detection of lesions
but also provides the additional capacity of
2 Setzer et al.
knowing the shape of a lesion, which, moving
forward, will aid in facilitating a subsequent
differential diagnosis.
MATERIALS AND METHODS
CBCT Selection
Institutional approval was obtained
(institutional review board #834136). Existing
deidentified CBCT volumes of 20 patients with
known age and sex were selected based on
criteria allowing for training and cross validation
of the DL algorithm to detect PLs. The
inclusion criteria were as follows: limited field of
view containing several roots with at least 1
periapical lesion per volume, teeth with or
without a history of endodontic treatment,
teeth with or without definitive coronal
restoration, and no to moderate presence of
scatter and/or artifacts. CBCT volumes were
normalized to contain the aforementioned
parameters. All CBCT images were acquired
using a Morita Veraviewpocs 3DF40 (Morita
Mfg, Kyoto, Japan) with a field of view of 40
mm at a voxel size of 125 mm from patients
referred for endodontic treatment. The reasons
for referral and subsequent treatment were not
recorded for this study. All CBCT volumes
were initially reviewed on 24-inch light-emitting
diode monitors (resolution 1920 ! 1200 at 60
Hz) using the proprietary software provided by
the CBCT company (iDixel, Morita Mfg). A PL
was identified when a disruption of the lamina
dura was detected, and the low-density area
associated with the radiographic apex was at
least twice the width of the periodontal
ligament space20–23.
Clinician-dependent CBCT
Segmentation and Labeling
Clinician-dependent CBCT volume
segmentation (referred to as clinician
segmentation [CS]) was performed using ITK-
SNAP (open-source) following protocols
established in previous studies23–25. From the
unprocessed CBCT images (referred to as
RAW), 5 standardized categories of image
content were identified and labeled: lesion (PL),
tooth structure, bone, restorative materials
(including root filling), and background
(everything else). For each label, the process
started with a semiautomatic segmentation
algorithm in the Active Contour segmentation
mode on ITK-SNAP, including the stages of
presegmentation (determination of the region
of interest), initialization (manual insertion of
seeds), and evolution (expansion of seeds
labeling the area of interest) (Fig. 1A–D). After
all labels were initially completed, each sagittal,
coronal, and axial slice was reviewed and
manually revised by 3 reviewers, if necessary.
All reviewers were calibrated and trained in
CBCT analysis and segmentation and included
an oral and maxillofacial radiologist (M.M.), an
endodontist (F.C.S.), and a senior graduate
student completing a radiology honors
program (K.J.S.). Disagreements were
resolved by joint discussion. After complete
segmentation and review, the most
representative sagittal region (traversing the
roots and PL if applicable) was determined,
including a center slice and 2 additional slices
in each buccal and lingual direction. Image
analyses was performed using standardized
monitor settings and lighting conditions.
CBCT Segmentation and Labeling
Using the DL Approach
All 20 pairs of deidentified RAW and clinician-
dependent processed CBCT volumes,
including the information on the representative
region, were forwarded to 3 experts in AI-
based biomedical image analysis (J.L., H.Y.,
and Z.Z.) at Arizona State University. By
remote training and discussion, an initial
version of the DL algorithm had been
developed to test the ability of DL in CBCT
segmentation and PL detection (referred to as
Deep Learning segmentation [DLS]). Briefly, a
multilabel U-Net26 was used as the baseline
architecture, focusing on the 5 labels specified
previously. A detailed description of U-
Net algorithms in general and its application in
biomedical image segmentation is provided
elsewhere27. For the 5 selected slices of each
CBCT image, individual U-Nets with shared
parameters were trained, respectively. In the
last layer of DLS, a 1 ! 1 3D convolution layer
was used to integrate information from the 5 U-
Nets for segmentation of the center slice
(Fig. 2). Because DLS was used to perform
multilabel segmentation, unequal weights for
the different labels were assigned in the loss
function throughout training. The label lesion
was attributed 8! the weight of the other
labels because it is the label with the most
clinical relevance. Furthermore, after DLS had
generated a segmented voxel-wise multilabel
map for each slice, the map was cleaned by
implementing automatic rules based on
domain knowledge of anatomic constraints of
PLs (eg, proximity to roots).
DLS was then taught to segment the 5
labels previously described based on 5-fold
cross validation. In detail, 20 CBCT images
were divided into 5 folds. Four folds (16 CBCT
images) were used for training, and the
remaining fold (4 CBCT images) was used for
validation. This process was iterated with every
fold used as the validation fold (ie, 5 total splits
of the data). The average DICE index of lesion
over the 5 iterations was used as the criterion
to optimize the DL algorithm. DICE is a
JOE  Volume -, Number -, - 2020
FIGURE 1 – CS. (A ) RAW CBCT image in the axial, coronal, and sagittal direction with identification of the region of interest (red box ). (B ) Initialization of segmentation by manual
insertion of seed points after presegmentation with thresholding. (C ) Final segmentation of tooth structure of lower anterior after seed point evolution and manual correction. (D ) Final
segmentation of all labels present in the image. Each color indicates a different label and was separately segmented.

commonly used metric to evaluate
segmentation accuracy. Please see the next
section for detailed definition.
Data Analysis and Statistical
Evaluation
Repeated splits of all images based on the 5-
fold cross validation were performed using
DLS, and the results were averaged. The
accuracy of CS versus DLS was evaluated by
the following 2 methods:
1. Lesion detection accuracy using a
dichotomized outcome of “presence of lesion”
and “absence of lesion” per lesion per root of
CS compared with DLS: CS was determined
by the 3 independent observers and based on
the probability index by Reit and Gro €ndahl28.
From a segmented image by DLS, the
presence of lesion or absence of lesion at each
root were naturally known and were put into a
confusion matrix in comparison with a CS
image. Based on the confusion matrix,
sensitivity, specificity, positive predictive value,
and negative predictive value were calculated
and graded according to the ranking for
diagnostic tests by Leonardi Dutra et al7 with
scores .80% considered excellent outcomes,
between 70% and 80% good, between 60%
and 69% fair, and ,60% as poor. Roots
without lesions served as controls.
2. Voxel-matching accuracy using the
DICE index calculated for each label: for
example for lesion, after our algorithm
generated a segmented image, we compared
the set of pixels labeled as lesion by the DLS
algorithm and the set of pixels labeled as lesion
by CS. Then, the DICE index of the lesion was
computed as twice the number of overlapping
pixels between DLS and CS divided by the
sum of the numbers of pixels in DLS and CS.
The more overlapping between the algorithm’s
segmentation and the manual segmentation,
the higher the DICE.
RESULTS
The data set contained CBCT images from 6
male and 14 female patients ranging from 19–
71 years old with a mean age of 44.4 years. All
reported results were based on cross
validation. DLS was able to distinguish
between the 5 labels described previously
(Fig. 3A–D).
Lesion Detection Accuracy
CS identified a total of 61 roots within all 20
CBCT volumes. On 29 of 61 roots (47.5%), the
presence of a PL was identified based on the
criteria outlined previously, and 32 of 61 roots
(52.5) had no lesions (Table 1). The initial
agreement between the reviewers was 27 of
29 lesions (93.1%). The 2 discrepancies were
resolved by joint review and discussion. DLS
identified 27 true-positive and 28 true-negative
situations. There were 4 false-positive and 2
false-negative accounts. For the dichotomized
lesion detection accuracy, sensitivity was 0.93
(excellent), specificity was 0.88 (excellent),
positive predictive value was 0.87 (excellent),
and negative predictive value was 0.93
(excellent), respectively.
Voxel-matching Accuracy (DICE)
The mean DICE index of lesion was used to
optimize our DL algorithm, which is 0.52 over
the 5-fold cross validation (standard deviation
5 0.15, range 5 0.36–0.70). The 2 false
negatives were the main source of variability for
the range of DICE because their respective
DICEs are 0. The mean values of the DICE
indexes for the other labels were tooth
structure 5 0.74, bone 5 0.78, restorative
materials 5 0.58, and background 5 0.95,
respectively. The cumulative DICE index for all
actual true lesions was 0.67. Table 1 details all

FIGURE 2 – DLS. Architecture of the DL algorithm for CBCT segmentation and lesion detection. Five slices from each CBCT volume were included in training, with individual U-Nets
built on each slice with shared parameters. These individual U-Nets were integrated by a 3D convolution layer in the end to segment the central slice. The DICE index of “lesion” on the
central slice averaged over 5-fold cross validation was used to optimize the parameters of this DLS design.

JOE  Volume -, Number -, - 2020 Artificial Intelligence for Detecting Periapical Lesions 3
FIGURE 3 – A case example of CS versus DLS demonstrated using a center slice. (A ) RAW: original CBCT slice. (B ) CS: rendering of the clinician-based segmentation. (C ) DLS:
intermediate step of multilabel segmentation applying different weights to individual labels. (D ) DLS: final multilabel segmentation after applying weights, anatomic constraints, and
additional data from adjacent CBCT slices. The red label represents “lesion.” Note the comparison with the RAW image and CS. DICE index for this lesion 5 0.88.

DICE indexes for actual true lesions and
individual labels for all samples.
DISCUSSION
This study investigated the use of artificial
intelligence, in particular DL, for the automated
detection of PLs in a localized CBCT
environment. Most PLs are indicative of apical
periodontitis and thus do not represent a life-
threatening disease unless they develop into a
severe acute apical abscess. However, apical
periodontitis is very prevalent, and the
implications on a patient’s general health are
still uncertain. The application of an automated
detection algorithm for CBCT images is
significant for a number of reasons.
Early detection of a PL may allow for
timely testing and a clinical differential
diagnosis with a potential of initiating
appropriate treatment. The majority of PLs
represent apical periodontitis, and early
detection may increase treatment success.
Apical periodontitis not only is a predictor of
success and failure20, but also it was shown
that teeth associated with larger apical
periodontitis show higher amounts of bacterial
endotoxins29. Thus, earlier treatment may
favor microbial disinfection before it
progresses to advanced stages. Many CBCT
scans are taken to evaluate a single tooth.
However, adjacent teeth contained in the
CBCT volume may demonstrate PLs that
might go unnoticed, particularly in situations in
which clinical evaluations such as thermal or
electric pulp testing deliver questionable
results (eg, the presence of porcelain-fused
restorations).
Artificial intelligence can reduce
interpretation bias. DL strategies
demonstrated superior performance over
conventional algorithms in biomedical image

TABLE 1 - An Overview of the Roots and Lesions Contained in the 20 Training and Validation Samples as well as DICE Indexes Overall per Individual True Lesion and Overall for Each
Label as Detected by Cone-beam Computed Tomographic Segmentation and Labeling Using the Deep Learning Approach

DICE index per actual true

lesions DICE index overall per label
Roots Roots Roots
per with without Lesion Lesion Lesion Tooth Restorative
Sample sample lesion lesion 1 2 3 Lesion structure Bone materials Background
#1 3 1 2 0.93 0.57 0.83 0.8 0.39 0.96
#2 4 1 3 0.93 0.57 0.79 0.85 0.68 0.94
#3 2 1 1 0.74 0.7 0.66 0.73 0.31 0.95
#4 2 2 0 0.76 0.78 0.69 0.72 0.86 0.55 0.95
#5 3 1 2 0.91 0.76 0.78 0.88 0.77 0.95
#6 3 2 1 0.87 0.78 0.67 0.42 0.48 0.56 0.94
#7 3 1 2 0.71 0.15 0.73 0.84 0.61 0.94
#8 4 2 2 0.94 0.25 0.76 0.7 0.87 0.66 0.93
#9 4 2 2 0.92 0.84 0.68 0.76 0.84 0.18 0.95
#10 4 3 1 0.84 0.86 0 0.51 0.78 0.82 0.76 0.95
#11 3 1 2 0.85 0.52 0.61 0.79 0.61 0.93
#12 2 1 1 0.74 0.15 0.42 0.75 0.6 0.96
#13 4 1 3 0.91 0.49 0.83 0.68 0.68 0.94
#14 2 1 1 0 0 0.91 0.63 0.72 0.94
#15 4 2 2 0.45 0.65 0.43 0.87 0.82 0.61 0.95
#16 3 2 1 0.3 0.42 0.31 0.76 0.8 0.62 0.95
#17 3 2 1 0.72* 0.64 0.76 0.64 0.72 0.97
#18 2 1 1 0.11 0.07 0.6 0.77 0.34 0.93
#19 2 1 1 0.19 0.14 0.79 0.79 0 0.97
#20 4 1 3 0.6 0.54 0.73 0.61 0.09 0.92
Total roots 61 29 32
Cumulative 0.67 0.52 0.74 0.78 0.58 0.95
DICE
index

*One large lesion surrounding 2 roots.

4 Setzer et al. JOE  Volume -, Number -, - 2020

analysis30,31. DL can automatically learn
rich features from an image. These range
from those perceivable by people, such as
intensity, shape, and texture, to those deeply
embedded in the image and beyond human
perception30,31. Thus, DL holds great promise
to overcome the CBCT image complexities
that complicate interpretation. In this limited
CBCT environment, our DL algorithm achieved
excellent lesion detection accuracy with a
sensitivity of 0.93 and a specificity of 0.88,
which was higher than achieved by a
convolutional neural network approach
evaluating panoramic radiographs for PLs
(sensitivity 5 0.65, specificity 5 0.87)14. Our
results were comparable with the cumulative
lesion detection accuracy by clinicians using
CBCT imaging (sensitivity 5 0.95, specificity 5
0.88) reported by a systematic review7.
However, the latter report included several
in vitro studies under idealized conditions.
DLS produced 2 false-negative reports.
One lesion missed was only minimally larger
than twice the width of the periodontal
ligament; the other was indeed detected by
DLS at first but eliminated in the final
postprocessing steps. This showed that DLS
achieved high consistency compared with CS
and superiority versus single slice-based
segmentation, even if a full-fledged 3D
algorithm, including all volume slices, was not
yet used. Although conventional DL strategies
require several thousand annotated training
samples, a U-Net architecture uses a network
and training strategy that applies data
augmentation to use available annotated
samples at high efficiency27. Thus, even a
small sample size of 20 image sets containing
61 roots could produce excellent lesion
detection accuracy, even if the samples were
not selected for pristine image quality. Only
CBCT volumes with severe beam hardening
artifacts (eg, from dental implants) were
excluded. Figure 3A exhibits an example of the
DLS capability to analyze images of moderate
quality.
Besides the detection of PLs, this DL
platform may have the potential to detect other
oral lesions (eg, for automated screening of
CBCT images for early detection of
nonodontogenic lesions, which, if overlooked
by human observers, may result in significant
treatment consequences at later stages of the
disease or medicolegal implications for the
practitioner). The long-term goal is the
development of the advanced platform AIDen
seamlessly integrated with clinical workflow
and providing decision support for clinicians.
U-Net architectures are fast27 and would thus
allow for time-efficient clinical integration.
Limitations of this study are the
comparison to CS, allowing for human error9.
Histology or high-resolution micro–computed
tomographic images could be used for
additional validation. Also, a direct comparison
to studies reporting the area under the receiver
operating characteristic curve (AUC) may be
limited. AUC calculation relies on the prediction
probability of individual labels derived from
probability vectors originating from the raw
output of DL algorithms. The advanced
algorithm used in this study applies cleaning
processes based on anatomic constraints,
making an AUC calculation unsuitable because
no raw output probability vectors remain after
label voxel fixation. Hence, the DICE index was
used in this study. Although DLS achieved
excellent sensitivity and specificity for lesion
detection accuracy, the DICE index ratios for
voxel-matching accuracy, particularly for
segmentation of the labels lesion and
restorative materials need improvement. The
reasons for a relatively lower DICE for these 2
labels were that the sizes of lesions were much
smaller than the other labels and that a variety
of different materials were combined into a
single label that inherently differed in shape,
location, brightness, and texture. These
limitations will be addressed by increasing the
training size, incorporating anatomic domain
knowledge into the DL design, and so on. The
multilabel approach does aid in this goal by
facilitating the baseline architecture of a true 3D
U-Net algorithm26. In addition, overall topology
estimation, location probability analysis, and a
domain knowledge approach extended to a
3D setting in combination with transfer learning
from pretrained DL on ImageNet32 and data
augmentation by image rotation and intensity
transformation can be incorporated. These
modifications, in combination with a larger
sample size derived from incremental samples
added into the training data, can be used to
further improve both lesion detection and
voxel-matching accuracy.
In the long-term, the addition of
automated image analysis based on 3D
imaging may aid clinicians with lesion detection
and, along with previous investigations,
differential diagnosis of periapical
pathology17,33–35 and/or nonodontogenic
lesions.
ACKNOWLEDGMENTS
The authors deny any conflicts of interest
related to this study.

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