diagnostics

Review
The Chairside Periodontal Diagnostic Toolkit: Past, Present,
and Future
Tae-Jun Ko , Kevin M. Byrd and Shin Ae Kim *

ADA Science & Research Institute, American Dental Association, Gaithersburg, MD 20879, USA;
[email protected] (T.-J.K.); [email protected] (K.M.B.)
* Correspondence: [email protected]; Tel.: +1-301-975-6805

Abstract: Periodontal diseases comprise a group of globally prevalent, chronic oral inflammatory
conditions caused by microbial dysbiosis and the host immune response. These diseases specifically
affect the tooth-supporting tissues (i.e., the periodontium) but are also known to contribute to
systemic inflammation. If left untreated, periodontal diseases can ultimately progress to tooth loss,
lead to compromised oral function, and negatively impact the overall quality of life. Therefore, it is
important for the clinician to accurately diagnose these diseases both early and accurately chairside.
Currently, the staging and grading of periodontal diseases are based on recording medical and
dental histories, thorough oral examination, and multiple clinical and radiographic analyses of the
periodontium. There have been numerous attempts to improve, automate, and digitize the collection
of this information with varied success. Recent studies focused on the subgingival microbiome and
the host immune response suggest there is an untapped potential for non-invasive oral sampling to
assist clinicians in the chairside diagnosis and, potentially, prognosis. Here, we review the available
toolkit available for diagnosing periodontal diseases, discuss commercially available options, and



highlight the need for collaborative research initiatives and state-of-the-art technology development

 across disciplines to overcome the challenges of rapid periodontal disease diagnosis.
Citation: Ko, T.-J.; Byrd, K.M.; Kim,
S.A. The Chairside Periodontal Keywords: periodontal diseases; oral diagnosis; dental equipment; periodontal probe; diagnostic
Diagnostic Toolkit: Past, Present, and imaging; biomarkers
Future. Diagnostics 2021, 11, 932.
https://doi.org/10.3390/diagnostics
11060932

1. Introduction
Academic Editor: Timo Sorsa
Periodontal diseases are a diverse group of chronic oral inflammatory conditions
caused by microbial dysbiosis and the host immune response. In a recent study of global
Received: 10 March 2021
Accepted: 19 May 2021
disease burden, periodontal diseases rank 11th of prevalent diseases in the world [1].
Published: 22 May 2021
According to the new criteria presented in the 2017 World Workshop, periodontal diseases
can be classified into dental biofilm-induced gingivitis, non-dental biofilm-induced gingival
Publisher’s Note: MDPI stays neutral
disease, necrotizing periodontal disease, periodontal manifestations of systemic disease,
with regard to jurisdictional claims in
and periodontitis [2–4]. For periodontitis, the disease severity, extent, and progression are
published maps and institutional affil- further classified based on multi-dimensional staging and grading systems [5]. Due to the
iations. heterogeneous clinical presentation of periodontal diseases, clinicians conduct multiple
diagnostic analyses at the chairside—often tooth-by-tooth—to make an accurate diagnosis
of both stage and grade. Several risk factors that may influence the condition, e.g., smoking,
diabetes, obesity, stress, and genetic susceptibility, are also systematically examined for a
Copyright: © 2021 by the authors.
more comprehensive diagnosis.
Licensee MDPI, Basel, Switzerland.
Clinical diagnostic analyses are generally based on the signs and symptoms of gingival
This article is an open access article
inflammation and periodontal tissue destruction. The major diagnostic tools commonly
distributed under the terms and used in the clinics are clinical observation (exam, photography), periodontal probing, and
conditions of the Creative Commons radiography. The tooth-supporting tissues, like the gums (i.e., gingiva), are observed
Attribution (CC BY) license (https:// for color changes, pain, edema, and positional changes, whereas the teeth themselves
creativecommons.org/licenses/by/ are examined manually for loosening and other direct signs of damage [6]. Moreover,
4.0/). the presence of plaque and calculus on teeth are examined. The use of the periodontal

Diagnostics 2021, 11, 932. https://doi.org/10.3390/diagnostics11060932 https://www.mdpi.com/journal/diagnostics

Diagnostics 2021, 11, 932 2 of 23

probe in the periodontal pockets around teeth provides information on pocket depth,
periodontal tissue loss (clinical attachment loss), and presence of bleeding upon probing
(i.e., a stimulating event). When these clinical observations and measurements with the
probe are combined with radiographs, the pattern and extent of alveolar bone loss can be
accurately evaluated. Only after collectively analyzing these data can the clinician ascribe
the disease’s stage and grade, which aids in planning treatment [7].
Although the clinical diagnostic analyses inform both periodontal disease diagnosis
and treatment, they are also inherently limited in that they can only assess disease history
but not disease activity [8]. This is because once periodontal disease initiates, it does not
follow a linear progression and can be characterized by periods of activity and remis-
sion [9,10]. To compensate for this limitation, many oral biomarkers from either oral fluid
(saliva, gingival crevicular fluid (GCF)) or oral rinse have been developed for periodontal
diagnosis, including host proteins, bacteria/bacterial products, ions, volatile compounds,
and additional genotypic/phenotypic markers [11–15]. This remains a nascent field, but
the incorporation of these biomarkers is expected to provide current disease activity and
risk factors associated with the disease, allowing early and accurate diagnosis [16]. In
this review article, (1) we summarize the current chairside periodontal diagnostic toolkit
focusing first on the commercially available probing tools for the advanced clinical exami-
nation of the gingival sulcus, (2) we present advances in dental imaging technology (from
two-dimensional to three-dimensional) for measurement of periodontal bone and tissues,
(3) we briefly introduce the chairside biomarker technology currently on the market, and
(4) we lastly summarize the future of chairside diagnosis and propose future research.

2. Diagnosis with the Available Chairside Probing Tools

2.1. Pocket Depth and Clinical Attachment Loss
Since chronic periodontal inflammation can lead to a loss of the supporting periodon-
tium, measuring the loss of this attachment has been a key criterion for classification of
the disease stage and grade and a strong predictor for future tissue destruction and thus
disease progression [17]. Generally, a periodontal probe is used to measure both clinical
attachment loss (CAL) and pocket depth (PD) (Figure 1a). CAL is defined as the distance
from the base of the pocket (coronal end of junctional epithelium) to the cementoenamel
junction (CEJ) of the tooth (hard tissue reference). In contrast, PD is the distance from the
base of the pocket to the gingival margin (soft tissue reference). Both CAL and PD have
been used as the defining periodontal disease analysis because each can be used to record
changes in the periodontal condition over time. However, the PD quantifies the tissue
loss without accounting for gingival margin level changes observed in gingival recession
or overgrowth, and while more time-intensive to measure, CAL is a considered better
diagnostic parameter to quantify the loss of periodontal attachment. Despite this, PD has
been commonly used and is still recorded by general dentists and periodontists [6,18]. The
2017 World Workshop has now standardized that CAL between teeth (the interdental CAL)
determines the periodontal disease classification [5].
There are many types of commercially available periodontal probes; however, manual
probes remain the gold standard in dental clinics for measuring CAL and PD. The manual
probes consist of a handgrip and probe tip. The tip design can range in length (12–16.5 mm
in length), thin (0.4~0.6 mm diameter), and shape of the working end (spherical end,
domed end, and a flat end with rounded corners) that can be inserted into the base of the
pocket. In addition, various types and colors of graduated scales are displayed on the probe
tip surface to help the manual reading of CAL and PD in millimeters (Figure 1b,c). For
standardization of the probe, a general requirement for manual stainless-steel periodontal
probes was specified by the International Organization for Standardization (ISO 21672-1
and -2:2012) [19,20]. However, even with these standardizations and specialized training,
manual periodontal probe measurements can vary significantly due to inter-examiner
differences in the probing force, probing angle, reading variations when reading man-
Diagnostics 2021, 11, 932 3 of 23

Diagnostics 2021, 11, 932 ual scales, clinician proficiency, and the unpredictable anatomy of periodontal pockets,
3 of 24
especially as the disease progresses [21].

Figure1.
Figure 1. (a)
(a) Schematic
Schematic presenting
presentingthe
themeasurement
measurementofofPD
PDbetween
betweenthe tooth
the and
tooth gingiva
and using
gingiva a a
using
periodontal probe with distance markings. (b) Various types of commonly used manual periodon-
periodontal probe with distance markings. (b) Various types of commonly used manual periodontal
tal probes and (c) specifications [19].
probes and (c) specifications [19].
There are many types of commercially available periodontal probes; however, man-
Several attempts have been made to correct these inconsistencies. For example, force-
ual probes remain the gold standard in dental clinics for measuring CAL and PD. The
controlled probes were designed that minimize the variation in probing force between clin-
manual probes consist of a handgrip and probe tip. The tip design can range in length
icians have been developed. The force-controlled probes typically apply a force of 0.20 N to
(12–16.5 mm in length), thin (0.4~0.6 mm diameter), and shape of the working end (spher-
0.25 N, allowing accurate diagnostic readings while minimizing patient discomfort [22,23].
ical end, domed end, and a flat end with rounded corners) that can be inserted into the
These include True Pressure Sensitive probe (TPS probe, Ivoclar Vivadent, Schaan, Liecht-
base of the pocket. In addition, various types and colors of graduated scales are displayed
enstein) and Pro-DenRx® Sensor Probe (Den-Mat Holdings, Lompoc, CA, USA). These
on the probe tip surface to help the manual reading of CAL and PD in millimeters (Figure
force-controlled probes are still operated manually but maintain constant probing force
1b,c). For standardization of the probe, a general requirement for manual stainless-steel
without electronic control. For example, the TPS probe has a sliding scale for visual guid-
periodontal probes was specified by the International Organization for Standardization
ance where two indicator lines meet at a specified force of 0.20 N. The visual-guided
(ISO 21672-1 and -2:2012) [19,20]. However, even with these standardizations and
probing allows the clinicians to apply a constant force through the end of the probe. In
specialized training, manual periodontal probe measurements can vary significantly due
addition to the visual guidance technique, electronic force-controlled probes were also
to inter-examiner differences in the probing force, probing angle, reading variations when
introduced by Polson in 1980 [22]. Polson’s probe allowed an electronically controlled
reading manual scales, clinician proficiency, and the unpredictable anatomy of periodon-
probing force that was constantly controlled at 0.25 N with an audio signal. This probe was
tal pockets, especially as the disease progresses [21].
further developed into the Yeaple probe, which is now used for dentinal hypersensitivity
Several attempts have been made to correct these inconsistencies. For example, force-
testing [24]. Despite the development of probing force control technology, measurement
controlled probes were designed that minimize the variation in probing force between
variation still exists due to the inter-examiner differences, and it is time-consuming to
clinicians have been developed. The force-controlled probes typically apply a force of 0.20
manually record and analyze a large amount of data accumulated in many sites (6 sites per
N to 0.25 N, allowing accurate diagnostic readings while minimizing patient discomfort
tooth).
[22,23]. These include True Pressure Sensitive probe (TPS probe, Ivoclar Vivadent, Schaan,
To reduce measurement variations caused by reading errors by eyes and save diagnos-
Liechtenstein) and Pro-DenRx® Sensor Probe (Den-Mat Holdings, Lompoc, CA, USA).
tic time, automated digital readouts and computer-aided recording and analysis techniques
These force-controlled probes are still operated manually but maintain constant probing
have been applied. The Florida Probe® (Florida Probe Corp., Gainesville, FL, USA) is one
force without electronic control. For example, the TPS probe has a sliding scale for visual
of the well-known computerized periodontal probing systems. The Florida Probe® consists
guidance where two indicator lines meet at a specified force of 0.20 N. The visual-guided
of a probe handpiece and sleeve, a displacement transducer, a footswitch, and a computer
probing allows the clinicians to apply a constant force through the end of the probe. In
interface with automatic charting. Through the coil springs inside the handpiece, the probe
addition to the visual guidance technique, electronic force-controlled probes were also
provides a constant probing force of 0.15 N. Based on the constant probing force, the PD
introduced by Polson in 1980 [22]. Polson’s probe allowed an electronically controlled
values are electronically measured with 0.2 mm precision and automatically transferred
probing force that was constantly controlled at 0.25 N with an audio signal. This probe
to the computer chart through the footswitch control or voice-activated software. Similar
was further developed into the Yeaple probe, which is now used for dentinal hypersensi-
electronic systems that can measure the PD include the InterProbe™ (Dental Probe Inc.,
tivity testing [24]. Despite the development of probing force control technology, measure-
Ashland, VA, USA) and the pa-on Parometer® (Orangedental GmbH & Co., Biberach, Ger-
ment variation still exists due to the inter-examiner differences, and it is time-consuming
many). The InterProbe™ is designed to reduce probing pain with a flexible probe tip, and
to manually record and analyze a large amount of data accumulated in many sites (6 sites
the pa-on Parometer® is designed to be easier to use with graphical and acoustic feedback
per tooth).
and an ergonomic wireless design. These advanced electronic probing systems eliminate
To reduce measurement variations caused by reading errors by eyes and save diag-
readout and recording errors and save diagnostic time for PD measurements. However,
nostic time, automated digital readouts and computer-aided recording and analysis tech-
despite the integration of computer-aided technologies and systemic automation, some
niques have been applied. The Florida Probe® (Florida Probe Corp., Gainesville, FL, USA)
is one of the well-known computerized periodontal probing systems. The Florida Probe®
consists of a probe handpiece and sleeve, a displacement transducer, a footswitch, and a
Diagnostics 2021, 11, 932 4 of 23

clinical studies have not found significant differences in accuracy or measurement vari-
ability between the electronic and manual probes when measuring the PD or CAL [25–28].
Moreover, the additional training and costs limit the clinical use of these electronic probing
systems.
Although several electronic periodontal probes have been successfully commercial-
ized for automatic PD measurements, measuring CAL has been even more challenging to
automate. The Foster-Miller probe (Foster-Miller, Inc., Waltham, MA, USA) was proposed
to control the probing force and electronically detect the position of CEJ for CAL measure-
ment. A ball tip of the probe is used to slide along the tooth’s surface at a controlled speed.
Once the tip reaches CEJ, the speed of the tip rapidly changes then moves to the base of the
periodontal pocket until it reaches the preset force. The CAL value can be electronically
calculated and recorded based on the controlled speed, preset force, slide time, and acceler-
ation time history. However, the prototype still requires further development, and it is not
commercially available yet.
Overall, incorporating new techniques (e.g., force-control, digitalization, and automa-
tion) has allowed the development of various types of periodontal probes, but only a few
have been accepted in clinics due to their complexity in operation, low cost-effectiveness,
and no significant improvements in accuracy nor reproducibility. The stainless-steel man-
ual probes are still the most commonly used diagnostic tools for CAL and PD. To achieve
better diagnostic accuracy and reproducibility, more innovation is still required. One
such example can be developing multifunctional probes using nanotechnology and mi-
crofabrication in probe design and fabrication. Another innovation could be attempted
in developing new probing protocols. Because the current probing protocol is done by
probing six sites per tooth sequentially, it is time-consuming and uncomfortable for patients.
Thus, more innovation and incorporation of new ideas will be the driving force for the
future development of periodontal probes.

2.2. Bleeding on Probing

Gingivitis and periodontitis weaken the gums (i.e., pocket ulceration), so bleeding can
occur during the probing of disease sites. For that reason, bleeding on probing (BOP) has
been considered as a sign of periodontal disease and is evaluated as a numerical indicator
called a BOP score [5,29]. The BOP score is assessed as a proportion of bleeding sites
within six tested sites on all present teeth when stimulated by a standardized probe with
a controlled force (0.2–0.25 N) to the bottom of the pocket. While the presence of BOP
can be a poor predictor of periodontal disease activity, the absence of BOP is an excellent
indicator of periodontal stability [30,31]. In the 2017 World Workshop, the BOP score was
also recognized as a basic parameter that set thresholds for the diagnosis of gingivitis and
assures the state of a healthy (BOP score < 10%) or gingivitis (localized: 10% ≤ BOP score
≤ 30%, generalized: BOP score > 30%) [32]. This was the first time that gingival health
had been defined, serving as an important benchmark for future diagnostic and prognostic
work.
To assess BOP, a binary readout (presence or absence) is performed, and manual
periodontal probes are most commonly used. To test for BOP, clinicians use a manual
periodontal probe to gently stimulate the tissue at the base of the periodontal pocket.
Once bleeding occurs at the probing sites, the number of bleeding sites is quantified as a
proportion of the total evaluated sites. When assessing gingivitis, dental floss or wooden
interdental cleaners can also be utilized to assess BOP as an initial evaluation of a patient’s
periodontal health [33,34]. However, some factors may influence BOP assessments, so
they should be carefully considered [35]. For example, BOP can be less noticeable in
smokers compared to non-smokers since smoking can cause gingival tissue keratinization
and vasoconstriction [7]. Additionally, the manual probing force also affects BOP since
the difference can lead to low reproducibility. In this case, force-controlled probes can be
utilized for BOP assessment to possibly increase reproducibility [34]. So far, no electronic
probe which automatically measures BOP score has yet to be commercialized. It is recently
Diagnostics 2021, 11, 932 5 of 23

reported that hemoglobin (Hb) presence in GCF suggests slight tissue damage, even in
healthy sites defined as an absence of BOP [36]. Therefore, the emergence of new probes
capable of detecting the bleeding (or Hb) within the periodontal pocket in a quantitative
way may help improve the utility of the analysis and increase the diagnostic sensitivity of
periodontal diseases.

2.3. Tooth Mobility

Tooth mobility is an important physical feature of periodontal diseases. When peri-
odontal diseases occur, it can cause bone resorption and damage to the supporting soft
tissues. As a result, the structure that holds the teeth firmly in place is lost, and the teeth
become mobile [37]. Tooth mobility is determined clinically by putting directional pressure
on the tooth and observing its movement. The Miller index is the most commonly used
manual method in which the tooth is held firmly between two instruments and moved
back and forth [38]. For a more accurate and reproducible evaluation of the degree of
tooth mobility, numerous techniques have been studied and tested. These include devices
of electronic registration [39], microperiodontometer [40,41], dental holographic interfer-
ometry [42,43], laser vibrometer [44], piezoelectric transducer [45], resonance frequency
analysis (RFA) [46], and non-contact vibration device [47,48].
Among various devices, the Periotest® M (Medizintechnik Gulden, Modautal, Ger-
many) is an electronic wireless device for assessing periodontal disease parameters (includ-
ing mobility) of teeth and osseointegration of dental implant [49,50]. The basic principle
of the device is based on measuring the response reaction from a reproducible impact,
which is applied to the center of the tooth surface. It measures contact duration per impact
between the rod and the tooth while an electrically controlled rod percusses the tooth and
then recoils. If there is any periodontal structural deviation in bone and/or soft tissue that
is caused by any periodontal disease, it will be reflected in the contact duration. Another
similar device, Implomates (Bio Tech One Inc., Taipei, Taiwan), percusses the tooth with a
metal rod driven by an electromagnetic field and records the induced vibrations using a
microphone with 50 Hz resolution. However, the output of these percussion tests lacks
reproducibility since they undergo significant changes as recording position and angulation
of the test device vary [51]. As a non-contact method, the Osstell IDx (Osstell AB, Gothen-
burg, Sweden) measures the implant stability (osseointegration) with non-invasive and
non-destructive techniques. This product utilizes RFA with resonance frequency ranging
from 3000 to 8500 Hz for an implant stability quotient of 0–100. The device consists of a
transducer, a computerized analysis module, and an excitation source [52,53]. Although
the Osstell IDx is optimized for osseointegration instead of natural tooth mobility test,
the device enhances patient comfort and increases reproducibility [51]. Therefore, it is
expected that the tools of tooth mobility test are also developed based on a non-contact vi-
bration technique to minimize the variations depending on the test position and operating
condition of the device.

2.4. Plaque and Calculus

Over 700 species of oral microbiome inhabit the human oral cavity, and about 400
species are found in the subgingival plaque [54]. Periodontal disease is driven by dysbiotic,
subgingival biofilms in susceptible hosts. These subgingival species secrete various com-
pounds that can cause tooth decay and periodontal tissue inflammation [55,56]. Moreover,
this irritation causes an inflammatory reaction that can lead to biofilm-induced gingivitis
and periodontal disease [4,32]. When the plaque is not removed effectively, calcium phos-
phate mineral salts in the saliva combine with the plaque between and within remnants of
formerly viable micro-organisms to develop calculus [57]. Calculus (colloquially referred
to as “tartar”) is also well known as a biofilm-retentive factor. Thus, teeth with calculus
show a significantly higher risk of attachment loss than teeth without calculus [58].
To examine the presence of plaque and calculus, sharp explorers or manual periodontal
probes have been typically used. Like with BOP, clinicians binarily assess the presence
Diagnostics 2021, 11, 932 6 of 23

or absence of this accumulated material. There are indices used in research to grade
plaque on more nuanced scales; however, these are not widely implemented in the clinic.
However, the traditional tactile assessment of the subgingival root surface without visual
accessibility lacks accuracy, specificity, and reproducibility. Since the average percentage of
accurate detections of clinically identifiable calculus depends on the clinical expertise, the
subgingival debridement may lead to varying degrees of residual calculus, removal of root
cementum, or both [59,60].
To overcome these shortcomings in identifying the calculus, several different technolo-
gies have been incorporated into the probe platform. The DetecTar (NEKS Technologies
Inc., Quebec, Canada) identifies subgingival calculus by evaluating the characteristic op-
tical signals on root surfaces and detecting spectro-optical differences between calculus
and the tooth surface. When the subgingival calculus is irradiated with a specific wave-
length light, it results in the production of a characteristic spectral signature caused by
absorption, reflection, and diffraction. These spectral signals are sensed by an optical fiber
and converted into an electrical signal for computer analysis. The shape and dimension of
the DetecTar probe tip are similar (0.45 mm diameter) to those of conventional periodon-
tal probes. The system is also available as a portable cordless handpiece with a curved
periodontal probe with millimeter scales to measure CAL and PD. As another tool, the
Perioscopy (Zest Dental Solutions, Carlsbad, CA, USA), which is a miniature periodontal
endoscope, is inserted into the periodontal pocket for subgingival visualization of the root
surface with tens of magnifications (maximum 48× magnification). This endoscope-based
system optically helps to identify the residual calculus spots during the examination. The
Diagnodent (KaVo Kerr, Brea, CA, USA) is a pen-like probe that sends a safe, painless
laser beam into the tooth to detect the autofluorescent signal from calculus lesions. The
Diagnodent can measure a wide range of fluorescence intensities that are displayed on a
digital display as a series of relative calculus detection values.
Furthermore, some products have combined the diagnosis and treatment functions for
clinical convenience. The PerioScan (Dentsply Sirona, York, PA, USA) provides a diagnosis
mode to detect calculus deposits and a treatment mode for the conventional ultrasonic
debridement with different power levels. When the ultrasonic tip detects calculus on
the tooth surface, blue light and an acoustic signal simultaneously are displayed on both
the handpiece and the display to facilitate diagnosis. The Key Laser 3+ (KaVo Kerr,
Brea, CA, USA) is another product that can conduct calculus detection and removal in a
feedback-controlled manner. The automated device contains a 655-nm InGaAs diode laser
for calculus detection and a 2940-nm solid-state erbium-doped yttrium aluminum garnet
(Er:YAG) laser for calculus removal. The Er:YAG laser is activated or inactivated depending
on the detected calculus level based on the feedback-controlled system. According to some
literature, there are no statistically significant differences between the feedback-controlled
laser debridement and the ultrasonic treatment [61,62]. The advantage of both systems
is that the diagnostic and treatment modes can be used continuously on the same tooth
surface without changing tools, but the specificity of the calculus detection still needs to
be improved. Especially, false detection, in which irregularities on the root surface are
erroneously recognized as calculus, remains a challenge to be solved.

2.5. Other Parameters with Diagnostic Potential

In addition to traditional clinical examinations, sensor-integrated probes also have
been used to measure additional disease-related parameters. Here, we introduce two
examples of chairside sensor-integrated probes based on auxiliary parameters: temperature
and sulfide concentration.
In general, the gingival temperature is increased by elevated blood flow and cel-
lular/metabolic reaction as a host-response to inflammation. The vascular changes are
accompanied during the inflammatory process (i.e., vasodilatation, increased vascular per-
meability, and increased blood flow), and the increased fluid transport in the inflamed site
raises the temperature. Therefore, temperature evaluation in the specific gingival area can
Diagnostics 2021, 11, 932 7 of 23

be clinically supported as an inflammation indicator [63–67]. Compared to a healthy site, a

temperature rise of 0.7–3.0 ◦ C was reported in the gingival sulcus (or gingival surface) with
periodontal disease [63–69]. The PerioTemp® probe (Abiodent Inc., Danvers, MA, USA)
has been used in many clinical studies for subgingival temperature measurement [67,68,70].
Key benefits of using this probe include a rapid response time (<1sec), high accuracy (±0.1
◦ C), and high reproducibility. Its physical shape and dimensions, similar to conventional

periodontal probes, allow the measurement of CAL, PD, and BOP as well as temperature.
It also has a computerized thermometer that displays actual subgingival temperature
(optional) and a risk level with two-color light indicators [21,67]. It has been reported
that this probe can help in the early diagnosis of periodontal disease and detect disease
activity by detecting subgingival temperature related to inflammatory changes [66,67]. In
addition, the performance of the PerioTemp® was reported to be comparable to that of an
infrared thermometer (Thermoscan® IRT 3520, Braun, Kronberg, Germany) with only about
0.18 ◦ C in the mean difference for the measured gingival temperature [71]. Although many
clinical trials evaluate periodontal disease progress or activity, the subgingival temperature
change assessment has not been perceived as a periodontal disease evaluation method [68].
Determining the normal temperature distribution can be very complicated as there is a
large variation between the patient, the location of the examination site, and the environ-
mental conditions (e.g., respiratory airflow and ambient temperature). For the subgingival
temperature to be recognized as a diagnostic parameter, further investigation is needed,
including the development of a new material showing better reliability and reproducibility,
the design of a new temperature probe that comprehensively considers various factors,
the standardization of a reliable measurement procedure, and the accumulation of data
showing clinical relevance.
It is well known that gram-negative bacteria are plaque-induced bacteria that generate
sulfur-related substances as by-products from their metabolism. These substances are
known to be volatile sulfur compounds (VSC), including hydrogen sulfide (H2 S), methyl
mercaptan (CH3 SH), and dimethyl sulfide (CH3 SCH3 ) [72]. When gram-negative bacteria
invade the underlying connective tissue of the periodontium, an inflammatory reaction
can begin and result in a tissue disruption [72]. Several clinical studies have reported
that sulfide by-products are associated with periodontal diseases, especially including
plaque-induced gingivitis [72–77]. Many sulfide detection tools have also been introduced,
e.g., Halimeter® (Interscan Corp., Simi Valley, CA, USA), Oral Chroma™ (Nissha FIS,
Osaka, Japan), and Breathtron® (Yoshida, Tokyo, Japan), but they are designed for halitosis
sensing and unavailable for diagnosing of PDs in the gingiva sulcus and periodontal
pockets. The Diamond Probe® /Perio 2000® System (Diamond General Development
Corp, Ann Arbor, MI, USA) is designed to detect sulfide levels in the gingival sulcus and
periodontal pockets in real-time for gram-negative bacteria monitoring. In this system, a
microscale sulfide sensor was incorporated into a modified Michigan O-type periodontal
probe to measure CAL, PD, BOP, and sulfide levels. When the sensor-integrated probe tip
encounters sulfides in the GCF, the system provides information in three ways: a four-color
light bar, an audible tone, and a sulfide level [75]. According to multiple clinical studies,
this sulfide probe demonstrated that the intra-pocket sulfide level is positively correlated
with the progression and severity of periodontal disease and was higher in untreated
subjects than maintenance subjects [72,74,78,79]. However, the sulfide probing system is
not commonly implemented in the clinic. The key reason is that the newly introduced
probe is still in the conceptual stage, and their cost-effectiveness does not offer a significant
advantage for periodontal disease diagnosis.
Since periodontal diseases are associated with systemic diseases, fast and accurate
diagnosis is becoming more important. Periodontal probe systems have made various
efforts to determine the PD and CAL with high accuracy and reproducibility. Additionally,
to provide additional evidence in periodontal disease diagnosis, various sensors (e.g.,
mobility sensor, calculus sensor, temperature sensor, sulfide sensor) have been integrated
into the probing tools. However, the probing tools commercialized so far are still at a very
Diagnostics 2021, 11, 932 8 of 23

early stage of development. Therefore, ongoing developments of probing tools, innovative

approaches, and collecting verifiable evidence will help in the early and accurate detection
of the risk of periodontal diseases, disease onset, and monitoring of oral health conditions
and systemic diseases (e.g., cardiovascular disease, diabetes, and inflammatory bowel
diseases) [80].

3. Diagnosis with the Imaging Tools

3.1. 2-Dimensional Imaging with Radiography
Conventional two-dimensional oral radiography is the most widely used imaging
method for diagnosing periodontal disease. The radiography minimizes patient discomfort
and pain in a non-invasive manner [81,82]. Conventional radiography provides a two-
dimensional (2D) image from a three-dimensional (3D) structure in the oral cavity and
reflects the anatomy of the hard tissues, including bone, cementum, dentin, enamel, and
calculus. The primary purpose of radiograph for periodontal disease assessment is to
measure the level of alveolar bone together with the observation of the factors including
bone level, bone destruction pattern, marginal contour, and extent of bone loss.
The common types of dental 2D radiography are panoramic and intraoral X-ray. The
panoramic X-ray captures the entire mouth with an overall view (a half-circle from ear
to ear) in a single image (Figure 2a). Since it visualizes the entire area in a single film,
including maxilla, mandible, and temporomandibular joints, it is useful for treatment
planning of extractions, implants, and dentures. Also, it is a reliable tool in observation
Diagnostics 2021, 11, 932
of alveolar bone loss caused by periodontal disease; however, this method is not suitable9 of 24
to diagnose the activity of periodontal disease since it hardly provides information about
periodontal soft tissues [83].

Figure 2. (a–c)
Figure Conventional
2. (a–c) 2D radiography.
Conventional 2D radiography.(a) Panoramic
(a) PanoramicX-rayX-ray
for capturing
for capturingthe entire mouth
the entire withwith
mouth an overall view.view.
an overall
Reprinted with permission from [84]. (b) Periapical X-ray and (c) bitewing X-ray for evaluation of
Reprinted with permission from [84]. (b) Periapical X-ray and (c) bitewing X-ray for evaluation of periodontal disease. periodontal disease.
Reprinted with with
Reprinted permission from from
permission [85]. (d)
[85].Digital subtraction
(d) Digital radiography
subtraction radiographyfor bone-regeneration assessment;
for bone-regeneration (I) baseline
assessment; (I) baseline
radiograph,
radiograph, (II) after
(II) after 12-month
12-month radiograph,
radiograph, andsubtraction
and (III) (III) subtraction
of (II)offrom
(II) from (I). Reprinted
(I). Reprinted with with permission
permission from from [86]. (e)
[86]. (e)
Deep learning-based periodontal bone-loss diagnosis; (I) panoramic radiograph, (II) bone-loss lesion annotated by clinicians,clini-
Deep learning-based periodontal bone-loss diagnosis; (I) panoramic radiograph, (II) bone-loss lesion annotated by
cians,
and (III) and (III)
bone-loss bone-loss
class class
activation mapactivation mapby
highlighted highlighted by the deep-learning-based
the deep-learning-based system. Reprinted system.
withReprinted
permission with
frompermission
[87].
(f) CBCT software interface including pan-map (top-right), horizontal section (top-left), vertical sections (bottom-right) and (bot-
from [87]. (f) CBCT software interface including pan-map (top-right), horizontal section (top-left), vertical sections
tom-right) and 3D reconstructed model (bottom-left). Reprinted with permission from [88]. (g) The depth and volumetric
3D reconstructed model (bottom-left). Reprinted with permission from [88]. (g) The depth and volumetric measurement of
measurement of the periodontal pockets using CBCT. Reprinted with permission from [89]. (h) 3D volumetric reconstruc-
the periodontal pockets using CBCT. Reprinted with permission from [89]. (h) 3D volumetric reconstructive CBCT image
tive CBCT image obtained from a patient with aggressive periodontitis. Reprinted with permission from [90].
obtained from a patient with aggressive periodontitis. Reprinted with permission from [90].
Intraoral X-rays take an image with a radiographic film or a detector placed inside
Intraoral X-rays take an image with a radiographic film or a detector placed inside
the mouth and are used in periapical views to provide precise and detailed information
the mouth and are used in periapical views to provide precise and detailed information
about each tooth and partial bone with various views. (Figure 2b). On the other hand,
about each tooth and partial bone with various views. (Figure 2b). On the other hand,
bitewing radiographs differ from periapical radiographs in that they are usually limited
to capturing the image of the 3–4 upper and lower teeth in one area of the mouth. A hori-
zontal bitewing radiograph is primarily used to detect bone height measurements along
the tooth root, while vertical bitewings are used to evaluate bone loss (Figure 2c) [91]. The
change of intraoral radiograph is used as important evidence of periodontitis progression.
Diagnostics 2021, 11, 932 9 of 23

bitewing radiographs differ from periapical radiographs in that they are usually limited to
capturing the image of the 3–4 upper and lower teeth in one area of the mouth. A horizontal
bitewing radiograph is primarily used to detect bone height measurements along the tooth
root, while vertical bitewings are used to evaluate bone loss (Figure 2c) [91]. The change
of intraoral radiograph is used as important evidence of periodontitis progression. In
addition, observation of furcation involvement based on intraoral radiographs can be
utilized to evaluate the amount of bone loss and tissue destruction [82].
Since digital radiography was first introduced to dentistry in 1987, it has rapidly
expanded to clinics by overcoming the shortcomings of traditional film-based radiography,
such as time and space constraints for printing [92,93]. Moreover, radiography obtained
with a digital detector can reduce the amount of radiation dose to the patient up to 90%
compared with film-based radiography due to the high sensitivity of the digital imaging
detectors [94]. Digital radiographs can be instantly displayed, stored, printed, and sent to
other electronics by use of a digital image capture device and a computer. Based on the
digital radiographs, the changes in bone density or volume can be easily recognized by the
contrast difference, i.e., lighter area refers to large bone density, and darker area refers to
bone loss. Furthermore, computer-aided image processing software enables high precision
analysis allowing easy assessment of disease severity and progression. Digital subtraction
radiography (DSR) is one of the representative technologies that use digitized radiographs.
DSR can record and superimpose two images of the same object obtained at different time
points, allowing for a visualized direct comparison (Figure 2d). An algorithm can then
subtract the image intensities from the identical pixel and automatically highlight the area
that has any differential. This technique allows the clinicians to easily diagnose tissue or
bone loss in a specific area by fading out of unchanged areas. One form of subtraction
radiography widely utilized in the research and clinic is computer-assisted densitometric
image analysis (CADIA). It uses a computerized video camera and an image analyzing
processor to measure the light that is transmitted through the radiographs. The light signals
that are converted to greyscale images can be mathematically processed. The quantitative
information results in two radiographs of the same anatomical location compared via
superimposition [95]. This then allows comparison and highlights any area with changes in
density possibly caused by bone density change or the existence of furcation involvement.
The CADIA system also evaluates bone regeneration in the extraction socket or the bone
density changes in a furcation [96,97]. Furthermore, in a recent study, deep learning
technology using artificial intelligence has been applied to automatically detect periodontal
bone loss in a 2D dental radiography (Figure 2e) [98,99].
Even though 2D imaging has been widely accepted as a standard imaging technique
for an oral health assessment, it contains some inevitable limitations while the 3D structural
information is presented in a 2D plane image by superimposition. Generally, image
distortion and blurring occur by the superimposition, hindering the accurate assessment of
delicate bone structures. For instance, the 2D imaging-based diagnosis of bone destruction
caused by periodontal disease tends to underestimate the actual severity [100]. To overcome
these limitations, various 3D-based imaging techniques that can reveal complex bone
structures have been introduced. These efforts help to determine a more accurate diagnosis
and plan for periodontal disease treatment.

3.2. 3-Dimensional Imaging with Computed Tomography

Computed tomography (CT), invented in 1972, has been used in oral health assess-
ment as an extraoral radiography method [82]. CT can build 3D image models without
superimposition of structures by assembling 2D cross-sectional images obtained from all
planes of interest. A study demonstrated that the alveolar bone height and intrabony
pockets could be precisely evaluated using CT assessment [101]. Although CT offers high-
quality 3D images with improved accuracy, increased radiation exposure and high cost are
concerns in adopting this periodontal disease diagnosis technique in dental clinics [102].
Diagnostics 2021, 11, 932 10 of 23

As an alternative option to conventional CT technology, a cone-beam computed

tomography (CBCT) has been introduced. The dental CBCT system allows a conical X-
ray beam to capture data from rotating around the patient with a ten-fold reduction in
radiation than conventional CT [103]. These data are then used to reconstruct 3D images of
the patient’s dental and maxillofacial areas (transverse section, sagittal section, and buccal
section) using software (Figure 2f). These reconstructed 3D models help the clinician clearly
understand the relationship between the lesion’s size and the surrounding anatomical
structures. It is also used to evaluate the progress of the disease and establish a treatment
plan. The 3D dental CBCT technology is more advantageous in bone and periodontal
pocket assessment than the conventional 2D radiography (Figure 2g,h) [89,90,104]. The
advantages and specifications of CBCT compared to the conventional 2D radiography are
summarized in Table 1. Up to date, various CBCT equipment have been commercially
available, including CS 9300 (Carestream Health, Rochester, NY, USA), Orthophos SL
3D (Dentsply Sirona, York, PA, USA), i-CAT FLX (KaVo Kerr, Brea, CA, USA), ProMax®
3D (Planmeca, Helsinki, Finland), PaX-i3D (Vatech, Hwaseong, South Korea), Prexion3D
(Prexion, San Jose, CA, USA).

Table 1. Comparison between 2D dental radiography and CBCT.

2D Dental Radiography
Techniques 3D CBCT
2D Intraoral X-ray 2D Panoramic X-ray
~20 lp/mm (Film) [105]
Resolution
6–15 lp/mm 1–4 lp/mm [106] 0.6–2.8 lp/mm [107]
(lp/mm)
(Digital) [105]
0.011–0.674 mSv (Dentoalveolar
0.005 mSv
CBCT with small and medium field
(Bitewing) [108]
0.003–0.024 mSv [108] Effective radiation dose view) [108]
0.035–0.171 mSv (Full-mouth
0.030–1.073 mSv (Maxillofacial
series) [108]
CBCT with large field of view) [108]
Provides axial, coronal, and sagittal
multiplanar images with
Periapical view- reconstructed
Provides overall view
Visualize the root apex, assess form without magnification.
(bird’s-eye view) of the
severe bone loss Pre-surgical bone quality
periodontium with the Features
Bitewing-Evaluate bone assessment for
minimized radiation
height, assess moderate to osteotomy and implant insertion
exposure.
severe bone loss [109]
Assessing crater defects and
furcation involvements [110]
3D imaging
2D imaging Cross-sectional and volumetric
Imaging method
Superpositions, distortion, and magnification models
No image deformation
High accuracy for detecting
Lower cost, lower radiation dose, relatively small device Advantages periodontal
bone defects [111,112]

For a series of axial cross-sectional images, tuned aperture computed tomography

(TACT) has also been utilized. It is designed to produce holographic images with 3D views
of teeth and pathology [113]. This equipment effectively detects the location of periodontal
bone gain or loss, alveolar contour, and even recurrent caries [113,114]. Cone-beam volu-
metric tomography (CBVT) is another CT-based technique that offers high resolution and
accuracy for assessment after regenerative therapy (e.g., bone fill or defect resolution) [115].
Quantitative computed tomography (QCT) offers more detailed bone mineral density infor-
mation with precise 3D anatomic localization of bone density assessment [116]. Moreover,
micro-focus CT can provide adequate information about the alveolar bone structure and
Diagnostics 2021, 11, 932 11 of 23

tooth morphology based on its fine spatial resolution (<10 µm). This technique enables
faster 3D image reconstruction and allows minimal side effects. In addition, 3D imaging of
interface in bone-implant has been reported using micro-focus CT [117].
Although radiation doses from advanced CT are generally lower than conventional
CT, 3D imaging with CT typically delivers more radiation than 2D radiography. Therefore,
the American Dental Association (ADA) and the US Food and Drug Administration
(FDA) recommend that clinicians perform dental radiography, including dental CBCT,
only when necessary to diagnose or treat the disease [104]. Efforts to reduce radiation
exposure and increase image resolution will continue in the future. Table 1 summarizes
the characteristics of 2D radiography and 3D CBCT, including effective radiation doses for
radiographic examination.

3.3. Ultrasonography
Diagnostic imaging with non-ionizing radiation can non-invasively evaluate the
structure and function of the human body without the risks associated with ionizing
radiation. Ultrasonography is a diagnostic imaging technique that exhibits the internal
tissue structure using reflections or echoes of ultrasound signals and is thus, non-ionizing.
The ultrasonic image uses a small probe to send ultrasound pulses (1~20 MHz in medical
diagnosis) to the tissue and displays the acoustic impedance of a 2D cross-section of tissue
based on the reflective properties of each tissue.
In dentistry, ultrasound was first used for diagnosis in 1963 [118]. Baum et al. tried
to observe the tooth’s internal structure using a 15 MHz transducer, but the image clarity
and quality were too poor to confirm a detailed structure. Afterward, based on advanced
imaging technology and software development, ultrasound devices for intraoral diagno-
sis were developed, including Krupp SDM® (Krupp Medizintechnik, Essen, Germany),
SonoTouch (Ultrasonix Medical Corporation, Richmond, Canada), IO3-12 (Alpinion, Seoul,
South Korea), and UltraSonographic Probe (US Probe, Visual Programs Inc., Ashland, VA,
USA). These instruments have been clinically applied to measure gingival lesions, tooth
fractures, soft tissue lesions, maxillofacial fractures, alveolar bone defects, and gingival
thickness [82,88,119–122]. In particular, the US Probe adopts the periodontal probe platform
with the tapered tip, which produces a narrow ultrasonic beam profile (~0.5 mm) using
a 1–20 MHz transducer. These ultrasonic waves are carried through an area created by a
small water stream into the periodontal pocket. The US probe can provide PD information
without probing pain as well as gingival tissue images with sufficient signal strength and
penetration depth along the gingival line [123].
So far, the use of ultrasound has not been widely adopted for disease diagnosis in
dentistry as an alternative method of radiography. However, recent studies demonstrated
that high-resolution ultrasonography clearly shows the cross-sectional morphological
images of the periodontal tissues, suggesting the possibility of applying ultrasound for
periodontal imaging. For example, Nguyen et al. reported that the alveolar crest level, the
CEJ location, and the alveolar crest’s thickness measured from ultrasonography presented
less than 10% of difference compared with those obtained from CBCT, proving ultrasound
can provide clinically reliable data [124]. Although ultrasound application in dentistry is
still in its infancy, it is believed to have massive potential as a diagnostic tool due to its
various benefits, e.g., portability, cost-effectiveness, free-of-ionizing radiation, and real-time
observation.

3.4. Magnetic Resonance Imaging

Based on its excellence for soft tissue imaging, magnetic resonance imaging (MRI) has
been considered a promising diagnostic tool in dentistry since 1981 [125]. MRI has exhibited
outstanding ability in soft tissue imaging among non-invasive diagnostic techniques,
allowing the MRI to have expanded its application for disease diagnosis in various medical
fields. MRI forms an image by measuring a pattern in which a hydrogen atom nucleus
absorbs and emits an electromagnetic wave in a magnetic field in the 0.2 to 7 Tesla (T)
Diagnostics 2021, 11, 932 12 of 23

range [126]. Since hydrogen is found in abundance as a form of water in soft tissue, MRI
can provide high contrast sensitivity to soft tissue, in contrast with CBCT that is specialized
in hard tissue imaging. A study conducted by Assaf et al. reported the visibility of osseous
and tooth-related structures using MRI. The result demonstrated that the region with
soft tissue (e.g., pulp chamber, apical foramen, mandibular nerve canal) presented good
visibility, while the enamel-dentin junction, cementum-dentin junction, and periodontal
space were challenging to visualize [127].
In recent years, MRI has been utilized for temporomandibular joint or jaw lesion
observation, pulp vitality evaluation, as well as endodontic treatment and implant plan-
ning [128,129]. In contrast, 2D radiography or CBCT specialized in the depiction of hard
tissue structures such as alveolar or mandible bone, MRI is adequate in visualization or
differentiation of the soft tissues. Therefore, it is capable of detecting the histopathological
change that occurs in the gingiva during the early stage of periodontal disease [130–132].
A recent comparison study between MRI and CBCT demonstrated that MRI is superior
to CBCT in the visualization of periodontal space and cortical/trabecular bone. Primarily,
MRI provided significantly better images for periodontal structures like lamina dura as
well as bone structure (e.g., cortical and trabecular bone), suggesting the high potential
capability of MRI in periodontal disease detection and periapical lesion observation [132].
Geibel et al. also reported that MRI could be more advantageous for accurate observation
of apical periodontal lesions compared to CBCT imaging in terms of characterization and
identification of periapical cysts and granuloma [133,134]. MRI also has been employed for
furcation involvement observation. The furcation involvement is one of the symptoms of
periodontal disease and occurs with bone resorption into the furcation area of a tooth root.
It has been typically evaluated using a curved periodontal probe in clinical assessment, but
it is challenging to accurately evaluate the severity due to complex root morphology and
limited accessibility of the probe [135]. In a study conducted by Alexander et al., MRI was
proven to demonstrate higher accuracy and reliability in imaging of furcation involvement
in maxillary molars compared to CBCT, allowing the accurate classification of furcation
involvement [135]. Based on several advantages in soft tissue imaging, MRI remains a
promising imaging tool for the diagnosis and treatment planning for periodontal disease.
Even though MRI devices were successfully applied for soft tissue imaging, the imag-
ing of hard tissues such as teeth, dentin, and enamel, which have low water content, is
inevitably restricted [136]. This poor visibility for hard tissue has been regarded as one of
the obstacles to the clinical implementation of MRI. However, a recent study suggested
overcoming the limitation of hard tissue imaging using MRI and demonstrating that using
MRI can be effective for both soft tissue and hard tissue observation. Algarin et al. designed
a special-purpose MRI scanner (DentMRI-Gen I) capable of producing high-quality com-
bined images of soft and hard biological tissues at sub-Tesla fields (260 mT) [137]. However,
simultaneous imaging of soft and hard tissues using MRI requires more clinical validation,
so there are remains opportunities for technology development. Some challenges that re-
main include the accessibility of equipment due to its high cost as well as the discomfort of
its use during long scanning time. The magnetic field may also cause metal-based implants
(e.g., hearing aid, cardiac pacemaker, or electrical stimulator) to malfunction and possibly
result in an injury. Lastly, higher technological expertise is required for MRI utilization
than for other imaging tools, which should be addressed to expand MRI application.

3.5. Digital Dental Photography

Digital dental photography is a type of macro-photography that provides information
on the surface of the oral cavity as part of the patient workup. Recently, there have been
reports of using digital photographs for examination, diagnosis, and treatment planning
of oral diseases [138]. With the advent of digital single-lens reflex (DSLR) cameras, dig-
ital photography has become photographic documentation to accurately record clinical
manifestations of the oral cavity. Correct color rendition with accurate exposure control
and sufficient resolution is essential to record salient features of both soft and hard tissue
Diagnostics 2021, 11, 932 13 of 23

details [139]. In specific, the correct color rendition of the photographs is an excellent
method for distinguishing between healthy and diseased soft tissue, including white
patches, inflammation, ulceration, carcinoma. In addition, digital photographs of sufficient
resolution can distinguish between healthy and diseased tissue by providing morphologi-
cal information such as gingival clefts and recession. Although digital photographs have
not yet been widely used for diagnosing periodontal diseases, their use in virtual patient
care is foreseen [140]. In addition, advances in the digital camera, optimization of image
processing, and automation of machine learning are expected to further expand the use of
digital dental photography in the future.

3.6. Intraoral Scanners

Intraoral scanners were developed to replace conventional dental impressions used
in prosthodontics, orthodontics, and restorative dentistry [141]. With the advancement
in computer-aided design and digital photography technologies, the digital intraoral
scanner has been successfully expanded the application based on its several advantages. It
projects a light source onto the object to be scanned and sends morphological information
to a connected computer system to render the 3D model with a digitized form. While
conventional dental impressions require complicated steps, the intraoral scanner can reduce
the time to obtain the information, which relieves patients’ pain and discomfort as well
as clinicians’ burden. Also, it is capable of real-time scanning and visualization, allowing
rapid diagnosis and communication based on the digitized result without concern of
potential deformation [142].
A few recent studies suggested that the digital assessment method using the intraoral
scanner is possible to apply in gingiva health assessment [143]. For example, oral scanners
were used to measure periodontal defects and evaluate tooth mobility, one of the parameters
evaluating periodontal disease [144,145]. Zhang et al. also reported that gingival volume
change in patients with periodontitis after therapy could be recorded using an intraoral
scanner. The results were positively correlated with other parameters, including PD,
bleeding index, and keratinized gingival width [143]. Intraoral scanning can also assess
gingival health or tissue regeneration by identifying the color difference in soft tissue.
Considering that there is a color difference between keratinized and nonkeratinized tissues,
it is possible to evaluate the keratinized mucosa’s dimensions [146]. In a study by Lee
et al., they used a 3D intraoral scanner with LED as a light source that is capable of color
recognition and claimed that the digital scanning could more accurately measure the
keratinized tissue width than using a periodontal probe [147]. This digital oral scanning
technology enabling color recognition is expected to expand its application as a simple and
promising tool for gingival health assessment and sulcus detection in the future [148]. To
date, several intraoral scanning devices have been commercially available, such as TRIOS 4
(3Shape, Copenhagen, Denmark), iTero Element® (Align Technology, San Jose, CA, USA),
CEREC Omnicam (Dentsply Sirona, York, PA, USA), and Emerald™ (Planmeca, Helsinki,
Finland).

3.7. Endoscopic Capillaroscopy

Another imaging technique for periodontal health assessment is endoscopic capil-
laroscopy. This technology can image and record the microvasculature of the periodontal
pocket and gingival crevice in vivo by inserting a sub-millimeter-sized optical fiber into
the periodontal pocket. It uses a green light with a wavelength of 520 nm for illumination
absorbed by both oxygenated and deoxygenated blood. The blood vessels with red blood
cells appear dark on a green background, allowing the high-resolution imaging of the
periodontal pocket microcirculation [149]. Although no cases have been reported for actual
periodontal disease evaluation, it is expected that the combination of capillary examination
and optical fiber technology can be used to observe the size change of microvessels caused
by periodontal disease.
Diagnostics 2021, 11, 932 14 of 23

4. Chairside Biomarker Detection

The heterogeneity of periodontal disease onset, patterning, activity, and treatment
response has hindered the accurate and reliable diagnosis of periodontal tissue infection.
For this reason, the symptom-based diagnosis techniques, e.g., use of periodontal probes or
dental imaging, can only provide the status about previous damages caused by periodontal
disease, but they are limited to obtain detailed information about disease activity that is
required for personalized treatment planning. However, with a recent understanding of
pathophysiology in periodontal diseases, various biomarkers (e.g., biochemical-, microbial-
, or genetic-based) have been suggested as having potential for improving diagnosis or
outcomes for better understanding of disease activity [8,11–13,32]. As inflammation further
processes due to periodontal disease, several types of mediators are released into GCF and
saliva as well as other oral rinses, thus they can be utilized as indicators through biomarker
assays. These biomarker assays are believed to help identify periodontal pathogens as a
readout of disease activity and for assessing periodontal disease severity. In addition, these
methods are expected to allow the clinicians to evaluate the prognosis after treatment for
any future treatments [11,12,150,151]. Although an ideal biomarker for periodontal disease
has yet to be identified, biomarkers that measure disease pathogenesis or bio-components
linked to tissue destruction, host defense mechanisms, and bacterial metabolism during
disease progression are actively being studied [8,152].

4.1. Biochemical Assay Kits

Efforts to develop a chairside biomarker assay kit for rapid periodontal disease di-
agnosis are continuing worldwide. For example, biochemical assay kits like PerioSafe®
PRO DRS (Dentognostics GmbH, Solingen, Germany) and ImplantSafe DR® (Dentognos-
tics GmbH, Solingen, Germany), which can measure active matrix metalloproteinase-8
(aMMP-8) in dental and medical clinics, were recently commercialized in Europe. MMP-8
is a major mediator of tissue destruction in periodontitis, and a correlation between in-
creased MMP-8 activity and progressive loss of connective tissue attachment and osteolysis
has been demonstrated through numerous clinical studies [11,12,153–155]. The PerioSafe
and ImplantSafe tests qualitatively measure aMMP-8 levels in oral rinse and GCF, respec-
tively [156]. In addition to the qualitative analysis, the PerioSafe and ImplantSafe test sticks
can quantify the amount of aMMP-8 in ng/mL units within 5 min. using the automated
digital device, ORALyzer® (Dentognostics GmbH, Solingen, Germany). According to
recent reports, the device with aMMP-8 assay kits is useful for distinguishing between
active and inactive sites with fast and easy analysis and detecting asymptomatic, ongoing
periodontitis before clinical and radiographic signs appear [153,157].
Other chairside biomarker assay tools using aspartate aminotransferase (AST) were
also developed. AST is an enzyme that is abundant in human gingival epithelial cells
and gingival fibroblasts. Upon cell death, a large amount of AST is released from the cell
cytoplasm into the GCF thereby, the level of AST in GCF can be used as a strong indicator
of gingiva tissue destruction [158]. PerioGard (Xytronyx, Inc., San Diego, CA, USA) and
PocketWatch (Steri-Oss Inc., Yorba Linda, CA, USA) are the chairside diagnostic tools that
diagnose periodontal disease by the assessment of AST level in GCF. In both products, the
activity of AST is evaluated based on the enzymatic catalysis reaction by comparing the
color of the collected GCF from patients with that of the controlled AST positive group.
In addition, to assess the risk of oral disease, a chairside saliva testing device using
test strips with multiple (6 to 7) indicators has been introduced in Japan. The SillHa
(ARKRAY Inc., Kyoto, Japan) and the Salivary Multi Test® (SMT® ; Lion Corp., Tokyo,
Japan) can measure multiple saliva indicators (blood, leukocytes, and proteins) related to
gingival health [159]. Both products consist of test strip kits and an automated wavelength
reflectometry device that reads color changes on the test strips within a few minutes
(~5 min). These toolkits of chairside biomarker assay in the market are summarized in
Table 2.
Diagnostics 2021, 11, 932 15 of 23

Table 2. Examples of biomarker assay kits in the market.

Biomarker
Sampling From Product Name Detecting Target Detecting Principle Analyzing in
Classification
Enzymatic digestion
GCF Periocheck Neutral proteases reaction
(Colorimetric assays)
Enzymatic catalysis
GCF PocketWatch AST reaction
(Colorimetric assays)
Biochemical Enzymatic catalysis
assay Chairside
GCF PerioGard AST reaction
(Colorimetric assays)
Oral rinse PerioSafe Lateral flow test with
aMMP-8 digital reader (OraLyzer® )
GCF ImplantSafe
Lateral flow test with
Blood, leukocytes, and
Oral rinse SillHa ST-4910 dual-wavelength
protein
reflectometry
Sandwich enzyme
Subgingival plaque Evalusite Aa, Pg, Pi immunoassay
(Colorimetric assays) Chairside
BANA-Enzymatic BANA hydrolysis reaction
Subgingival plaque Pg, Td, Tf
test kit (Colorimetric assays)
OMNIgene ORAL/ Characterization of
Gums and plaque
OMR-110 DNA hybridization
virus species of all
OMNIgene ORAL/ genome type including Aa,
Saliva Pg, Pt, Fn, Td, Ec
OM-501, 505
Microbiological
assay Carpegen® Perio
Subgingival plaque Aa, Pg, Tf, Td, Fn, Pi Real-time qPCR
Diagnostik
Company or
Aa, Pg, Td, Tf, En, Fn, Pi, Cr,
Oral rinse MyPerioPath® DNA hybridization research
Pm, Ec, Cs laboratory
Microbiological
samples/subgingival iai Pado Test Aa, Pg, Pi, Td, Tf, Fa DNA hybridization
plaque
Aa, Pg, Pi, Tf, Td, Pm, Fn, Cr,
Subgingival plaque micro-IDent® plus11 DNA hybridization
En, Ec, Cs
Cheek swab PerioPredict™ genes for IL-1 DNA hybridization
Company
Genetic assay MyPerioID® IL-6 or Genetic polymorphisms
laboratory
Oral rinse genes for IL-6 or IL-1
IL-1 detection
GCF: Gingival crevicular fluid, AST: Aspartate aminotransferase, aMMP: active Matrix metalloproteinase, Aa: Aggregatibacter actino-
mycetemcomitans, Pg: Porphyromonas gingivalis, Pi: Prevotella intermedia, Td: Treponema denticola, Tf: Tannerella forsythia, Fn:
Fusobacterium nucleatum, Ec: Eikenella corrodens, En: Eubacterium nodatum, Fn: Fusobacterium nucleatum/periodonticum, Cr: Campy-
lobacter rectus, Pm: Peptostreptococcus (Micromonas) micros, Cs: Capnocytophaga species (gingivalis, ochracea, sputigena), Fa: Filifactor
alocis, IL: Interleukin, qPCR: quantitative polymerase chain reaction.

4.2. Microbiological Assay Kits

Microbiological diagnostic tools also have been widely studied. It has been found
that over 700 species of oral microbiome related to oral disease, and some are significantly
associated with periodontal disease and can be used as microbiological biomarkers for the
disease diagnosis [54]. To date, the onset of periodontitis is related to pathogens including
Porphyromonas gingivalis (Pg), Treponema denticola (Td), Tannerella forsythia (Tf), Actinobacillus
actinomycetemcomitans (Aa), Prevotella intermedia (Pi), Fusobacterium nucleatum (Fn), and
Filifactor alocis (Fa) [158]. These bacteria generally co-locate in periodontal pockets with a
wide distribution and increased numbers suggesting that these can be potential biomarkers.
Some periodontal pathogens, including Pg, Td, Tf, and some Capnocytophaga specie, produce
bacterial trypsin-like proteases by utilizing the hydrolysis reaction of BANA (N-Benzoyl
D-L Arginine -2 Naphalamide) in the biofilm. Thus, based on this hydrolysis reaction, the
BANA-Enzymatic test™ kit (Ora Tec Corporation, Manassas, USA) is developed as rapid
Diagnostics 2021, 11, 932 16 of 23

and reliable chairside diagnostic tests. The Evalusite (Eastman Kodak company, Rochester,
NY, USA) is a rapid microbiological assay kit that detects three recognized pathogens: Aa,
Pg, and Pi. By collecting a subgingival plaque, the kit detects the presence of the pathogens
based on an antibody-bounded sandwich-type enzyme-linked immunosorbent within
10 min. As a chairside diagnostic platform, OMNIgene (DNAgenotekTM , Ottawa, ON,
Canada), iai PadoTest (IAI AG, Zuchwil, Switzerland), MyPerioPath® (OralDNA Labs,
Eden Prairie, MN, USA), micro-IDent® plus11 (Hain Lifescience GmbH, Nehren, Germany),
and Carpegen® Perio Diagnostik (Carpegen GmbH, Münster, Germany) have also been
introduced. They detect several periodontal disease-related pathogens in collected saliva,
oral rinse, or plaque based on nucleic acid-based assays. However, many of the microbial
assay kits are available in laboratories with some expensive equipment.

4.3. Genetic Assay Kits

Analyzing the genetic “susceptibilities” may also help identify or anticipate the po-
tential risk of periodontal disease initiation and progression. It has been known that the
polymorphism in the interleukin-1 (IL-1) gene has been shown to be proinflammation-
causing periodontal disease [7]. To identify the genetic risk of periodontal disease, multiple
test kits have been introduced in the market, including PerioPredict™ (Interleukin Genetics,
Inc., Waltham, MA, USA), and MyPerioID® (IL-6 and IL-1; OralDNA Labs, Eden Prairie,
MN, USA). However, these tests require significant laboratory equipment or additional
time to deliver the sample to the manufacturer’s laboratories for data analysis. Thus, these
kits cannot be truly recognized as chairside diagnostics.
Despite several efforts on finding biomarkers, biomarker-based detection has been oc-
casionally applied in dental offices. One reason for the low practical use of biomarker-based
techniques is the lack of standardized assays. In addition, there is still no FDA-approved
saliva diagnostic test or point-of-care technology for clinical diagnosis of periodontal dis-
eases in the United States (as of September 2020). The good news is that the practical
application of biomarkers in periodontal disease diagnosis starts to be discussed in dental
research society. In the 2017 World Workshop, the introduction of biomarkers was strongly
encouraged as a supportive indicator to identify periodontal disease and to estimate its
stage and grade [5]. So far, the specific biomarkers and their thresholds have not been estab-
lished yet, but we expect they will be incorporated and used in periodontal disease grade
assessment as evidence will become available soon. Efforts to accelerate the development
of chairside periodontal assay kits or automated biosensors by combining clinically rele-
vant biomarkers with lab-on-a-chip or point-of-care technologies are still active [8,11,158].
Compared to conventional labor-intensive and time-consuming laboratory procedures,
the automated chairside periodontal assay methods are believed to provide immediate
analysis results related to the disease. Moreover, technologies will evolve toward improv-
ing diagnostic sensitivity and accuracy by analyzing multiple analytes simultaneously,
although the size of the biosensor is reduced. Furthermore, the ability of chairside analysis
of biomarkers for accurate diagnosis and prognosis of the disease will be an important
advantage in preventing irreversible damage to periodontal bones and tissues.

5. Future Directions
Manual periodontal probing and 2D radiography have been the two major diagnostic
tools for periodontal disease. Over the years, various new technologies have been incorpo-
rated into these two diagnostic tools in attempts to improve their accuracy, reproducibility,
speed, and patient comfort (Figure 3). For periodontal probing in clinical examination,
early attempts at improvements were derived from the incorporation of advanced mechan-
ical and electrical technologies that enabled accurate and automated assessment. Various
sensors (e.g., calculus, temperature, sulfide, and pressure) are being integrated into the
periodontal probe platform to provide new information inside the periodontal pocket for a
comprehensive analysis. With the development of microfabrication and nanotechnology
in the coming years, these sensors are further expected to be miniaturized and integrated
Diagnostics 2021, 11, 932 18 of 24
Diagnostics 2021, 11, 932 17 of 23

observation, and based on this, it started to gain considerable interest from the periodontal
disease
into theresearch community
probe for [137,160].
multifunctional Lastly, Furthermore,
analysis. with the integration of state-of-the-art
the approach im-
of non-invasive
age processing algorithms and artificial intelligence technology, higher accuracy in
technology that can quickly and accurately provide 3D information of the diseased area is diag-
nosis and better
expected prediction
to reduce patientinpain
prognosis are expected [98,99,161–163].
and discomfort.

Advancementofofchairside
Figure3.3.Advancement
Figure chairside periodontal
periodontal diagnostic
diagnostic tools
tools and
and their
their future
future directions.
directions.

As radiography
Although the current technology
standardisinbecoming
the diagnosis more of developed,
periodontal the radiograph
diseases imaging
is still mainly
of the periodontal lesions has gained more significance in periodontal
based on clinical examination and diagnostic imaging, recent advances in biomarkers pro- health assessment.
In particular,
pose the development
a new possibility in early-stage of 3D imaging
detection andtechnology like CBCT
rapid diagnosis. allowed
To date, accurate
large-scale
visualization of bone destruction, which then enabled the
laboratory assays and many clinical trials have been conducted to identify candidate precise diagnosis of disease
bi-
severity and progress. Moreover, since 3D imaging technology
omarkers. Moreover, some promising biomarkers have been reported for simultaneous is reported to successfully
visualize bone
multi-analyte and soft
sensing tissue using
to promote various
diagnosis radio-opaque
accuracy. Based onagents, an accurate 3Dit map
these developments, is
of the periodontal pocket morphology is expected to be
plausible to believe that automated chairside diagnostic protocols with effective possible without painful tactile
bi-
examination
omarkers for patients
will soon be availablein the[158].
future [93]. However,
Overall, the diagnosis diagnostic
methodsradiography
for periodontal exposes
dis- a
patient to doses of ionizing radiation. As an alternative to
eases have continuously advanced with the incorporation of various technologies. It willradiography, other imaging
betechnologies
no surprise without
that this ionizing
trend willradiation
continue(e.g.,
as weultrasonography
experience moreor MRI) are being
technological actively
advance-
studied. It was recently found that a method using MRI can
ment and pathological/biological understanding. By embracing new technological devel- be used for both soft tissue
and hard tissue observation, and based on this, it started to gain
opments, clinicians may expand their chairside toolkits to identify, treat, and manage per- considerable interest
from thediseases.
iodontal periodontal disease research community [137,160]. Lastly, with the integration of
state-of-the-art image processing algorithms and artificial intelligence technology, higher
Funding:
accuracyThis research was
in diagnosis andfunded
betterbyprediction
ADA Foundation, grant number
in prognosis 97700140.
are expected [98,99,161–163].
Although theThe
Acknowledgments: current
authors standard in the
would like diagnosis
to thank of periodontal
the ADASRI colleaguesdiseases
for their is still mainly
administra-
based
tive and on clinical
technical examination and diagnostic imaging, recent advances in biomarkers
support.
proposeofa Interest:
Conflicts new possibility
The authors in declare
early-stage detection
no conflict and rapid diagnosis. To date, large-
of interest.
scale laboratory assays and many clinical trials have been conducted to identify candidate
References biomarkers. Moreover, some promising biomarkers have been reported for simultaneous
multi-analyte sensing to promote diagnosis accuracy. Based on these developments, it is
1. Vos, T.; Abajobir, A.A.; Abate, K.H.; Abbafati, C.; Abbas, K.M.; Abd-Allah, F.; Abdulkader, R.S.; Abdulle, A.M.; Abebo, T.A.; Abera,
S.F.; et al. Global, regional, and national to
plausible believeprevalence,
incidence, that automated chairside
and years lived withdiagnostic
disabilityprotocols with effective
for 328 diseases biomarkers
and injuries for 195
will soon be available [158]. Overall, the diagnosis methods
countries, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017, 390, 1211–1259, for periodontal diseases
doi:10.1016/S0140-6736(17)32154-2.have continuously advanced with the incorporation of various technologies. It will be no
2. Herrera, D.; Retamal-Valdes, surprise that this
B.; Alonso, trend will
B.; Feres, continue
M. Acute as we experience
periodontal more technological
lesions (periodontal abscesses advancement
and necrotizing and
periodontal diseases) and endo-periodontal lesions. J. Clin.
pathological/biological Periodontol. 2018,
understanding. By45,embracing
S78–S94, doi:10.1111/jcpe.12941.
new technological developments,
3. Jepsen, S.; Caton, J.G.; Albandar, J.M.; Bissada,
clinicians may expandN.F.; Bouchard, P.; Cortellini,
their chairside toolkits P.; to
Demirel, K.; de
identify, Sanctis,
treat, and M.; Ercoli,periodontal
manage C.; Fan, J.
Periodontal manifestations ofdiseases.
systemic diseases and developmental and acquired conditions: Consensus report of workgroup

Funding: This research was funded by ADA Foundation, grant number 97700140.
Diagnostics 2021, 11, 932 18 of 23

Acknowledgments: The authors would like to thank the ADASRI colleagues for their administrative
and technical support.
Conflicts of Interest: The authors declare no conflict of interest.

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