Clinical Evaluation and Patient Experience of a Stationary Intraoral Tomosynthesis (s-IOT) Unit Using a Carbon Nanotube X-ray Source Array
Phase: NA
Conditions: Dental Caries
Sponsor: University of North Carolina, Chapel Hill

 
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“Clinical evaluation and patient experience of a stationary intra-oral 
tomosynthesis (s-IOT) unit using a carbon nanotube x-ray source array” 
 
 
Protocol Number: 16-0194 
 
National Clinical Trial (NCT) Identified Number:  NCT02873585 
 
Principal Investigator: Angela Broome 
 
Sponsor: University of North Carolina at Chapel Hill, Adams School of 
Dentistry 
 
Grant Title: NC TraCS Improving Human Health Awards 
Grant Number: IHHAR21506 
 
Version Number: 1.0 
2017-11-13 
 
 
 
 

 
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Table of Contents 
1. 
SIGNIFICANCE .................................................................................................... 3 
1.1. 
Improving caries detection is a high oral health priority ..................................... 3 
1.2. 
We have invented a new technology with significantly increased sensitivity ...... 3 
1.3. 
Pathway for clinical translation and commercialization ...................................... 4 
2. 
INNOVATION ....................................................................................................... 5 
2.1. 
s-IOT enabled by the CNT x-ray source array technology ................................. 5 
2.2. 
Preliminary results: s-IOT outperforms current dental imaging modalities. ........ 6 
2.3. 
We have an experienced interdisciplinary team ................................................. 7 
3. 
APPROACH ......................................................................................................... 7 
3.1. 
SPECIFIC AIM 1: Characterization and Certification of Prototype Device ......... 7 
3.2. 
SPECIFIC AIM 2: Clinical Evaluation and Patient Experience ........................... 8 
4. 
RISK AND REMEDY ............................................................................................. 9 
5. 
REFERENCE ........................................................................................................ 9 
 
 
 

 
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1. SIGNIFICANCE 
1.1. Improving caries detection is a high oral health priority 
 
Caries is the world’s most common dental disease. The WHO estimates that 60-
90% of school children and nearly all adults 
have dental caries at some point in time(1). 
If carious lesions are detected early enough, 
i.e. before cavitation, they can be arrested 
and remineralized by non-surgical means. 
When left undetected, they could evolve into 
more serious and destructive conditions that 
may require expensive restorations, 
endodontic treatment, and, in some cases 
extractions. Despite advances made in 
dental imaging including digital detection and 
computed tomography (CT), the diagnostic 
accuracy for caries has not seen significant 
improvement in many years and remains low.   
The sensitivity of 2D intraoral radiography, the current gold standard for caries 
diagnosis, ranges from 30% to 70% for different types of caries, due to the fundamental 
limitation of structure superimposition (2, 3). Cone-beam CT (CBCT) requires as much 
as 100X the radiation, but does NOT improve caries detection due to its inferior 
resolution and imaging artifacts compared with intraoral imaging (4-8). The diagnostic 
accuracy for some other common dental conditions such as root fractures, and 
periodontal bone loss (Figure 1) have also remained low (9, 10). There is a clear 
clinical and market need for better diagnostic technologies. 
1.2. We have invented a new technology with significantly increased sensitivity   
Our invention, stationary intraoral tomosynthesis (s-IOT), overcomes the 
limitations of the current dental imaging technologies for diagnosis of dentoalveolar 
diseases(11, 12). It provides depth information and removes structural overlaps that 
obscure anatomical details in 2D imaging. It offers better in-plane resolution, less 
 
 
 
Figure 1: 1st row: 2D intraoral x-ray 
(left) and dental CBCT (right). 2nd row: 
schematics of caries, vertical root 
fracture and periodontal bone loss, 
which are difficult to detect with the 
current technologies. 

 
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imaging artifact, and faster 
image acquisition at lower 
dose and cost comparing to 
CBCT (Figure 2). Our 
preliminary results have shown 
that s-IOT provides significantly 
increased detection sensitivity, 
more accurate assessment of 
lesion depth and improved 
interpretation ease across a 
wide variety of clinical settings 
compared to the current dental 
imaging technologies.  
The clinical applications of s-IOT are not limited to caries detection, but include 
secondary caries detection, root fracture detection, alveolar bone assessment, root 
anatomy and periapical assessment, 3D assessment of dental developmental 
anomalies, and preliminary implant site assessment.  Early disease detection and 
treatment will promote the oral health of patients worldwide. 
1.3. Pathway for clinical translation and commercialization 
 The dental community has received the s-IOT technology enthusiastically. Over 
80% of the 250 NC dentists surveyed expressed interests in purchasing this device at 
our estimated price range. The research won an award from the dental association, and 
was recently featured in “Dentistry Today” and on the WRAL Evening News 
(http://wral.com/14923174). 
Steps toward translation and commercialization: (1) The feasibility study was 
performed with funding from a recently completed NIH SBIR grant; (2) Two patent 
applications were filed by UNC and licensed by Xintek; (3) Xintek formed a new 
subsidiary XinVivo to commercialize the technology; (4) Seed equity investment has 
been secured to construct the first clinical prototype; and (5) Potential partnerships with 
market leaders (Carestream Dental and Planmeca) are under discussion.  
 
Key features:  
 Significantly higher 
sensitivity than 2D x-ray 
and CT 
 Low dose (same as 2D 
intraoral) 
 Low cost compared to 
CT 
 Short image time (1 s) 
 Seamless integration 
with current data 
management system 
 Perform all tasks of 
current 2D intraoral  
Figure 2:  An illustration of the s-IOT device and its key 
advantages comparing to 2D intraoral and CBCT. 

 
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This NC TraCS grant is critical to fund the first patient evaluation at the UNC Oral 
and Maxillofacial Radiology Clinic, and to further advance the technology.   
2. INNOVATION 
2.1. s-IOT enabled by the CNT x-ray source array technology  
Digital tomosynthesis uses a series of limited-angle projection images to produce 
a 3D representation of the object (13).  A variation of this technique called Tuned 
Aperture CT(14) (TACT) was shown to improve the diagnostic accuracy for a number of 
tasks compared to 2D intraoral x-ray in bench-top phantom studies (14, 15). The 
technology however was not feasible for patient imaging. It took ~30 minutes for a scan 
(vs. ~ 1 s for a 2D x-ray) and required high operator skills for positioning, because the x-
ray tube needed to be precisely moved and positioned at different locations to acquire 
the multiple projection images. The image reconstruction time was also very long due to 
inefficient algorithm.   
The working mechanism of s-IOT is illustrated in Figure 3:  (1) A carbon nanotube 
(CNT) x-ray array technology invented by our team at UNC(16-18) is utilized to 
generate a scanning x-ray from different directions without any mechanical motion; (2) A 
high-frame-rate digital intraoral sensor captures the projection images in 
synchronization with the x-ray exposure; (3)  

 
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 An optical pattern recognition 
method developed in our lab is used to 
determine the imaging geometry; and 
(4) A high-speed iterative 
reconstruction algorithm written by us 
(19) processes the projection images to 
generate tomosynthesis image slices in 
real-time.  In s-IOT, a complete 3D 
scan takes less than 1 second; the total 
imaging dose used is the same as a 
single 2D intraoral radiograph.  The 3D 
tomosynthesis slices are reconstructed 
and displayed layer by layer in the 
depth direction to “virtually dissect” the 
object. 
2.2. Preliminary results: s-IOT outperforms current dental imaging modalities.   
 A bench-top s-IOT device was constructed and used for evaluation and system 
optimization. The performance was compared with clinical 2D intraoral x-ray by imaging 
phantoms (20) and extracted human teeth. Figure 3 shows examples of phantom 
images where: (1) carious lesions are missed or barely discernable on the 2D image 
(B), but are clearly visible in the tomosynthesis reconstruction slices (C,D); (2) s-IOT 
clearly resolved the front and back roots of the upper molar teeth (C, D) that was 
overlapped in the 2D image (B);  and (3) s-IOT identified root fractures (D) that was 
missing in 2D (B).  
A reader study was performed with eight experienced UNC dental radiologists 
reviewing the images of the extracted human teeth taken from s-IOT and 2D intraoral. 
Micro-CT images served as the ground truth.  The results showed that the average 
sensitivity of s-IOT increased by 36% compared to that of 2D intraoral, the largest 
reported increase by any modality in modern dental imaging, without compromising 
specificity or increasing the imaging dose.  
 
 
 
Figure 3: (A) conceptual illustration of s-IOT. 
(B) x-ray image of a phantom using clinical 2D 
intraoral x-ray. Reconstructed s-IOT image 
slices of the same phantom, at two different 
depths, showing: 1) mesial and distal buccal 
roots (C) and the palatal (D), 2) all 3 simulated 
caries, and 3) fracture (D). In contrast, 2D x-ray 
(B) did not resolve the root structure, missed 
one caries, and missed the fracture(12).  

 
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2.3. We have an experienced interdisciplinary team 
Our team of physicists (Zhou, Lu) and maxillofacial radiologists (Platin, Mol) are the 
inventors of the s-IOT technology, with extensive experience in developing and 
translating medical devices (21-23), clinical dental imaging, and commercialization. NC 
TraCS statistician (Zeng) will help perform the statistical data analysis. Zhou and Lu 
invented the CNT x-ray source array, the key enabling technology. We developed a 
novel micro-CT scanner, installed at UNC and Iowa for biomedical research; a 3D 
mammography system and a 3D lung imaging device, currently under clinical 
evaluation. Zhou and Lu have equity stakes in Xintek, the UNC spin-off.  
A conflict of interest committee has been established at UNC to oversee potential COI 
issues.  
3. APPROACH 
3.1. SPECIFIC AIM 1: Characterization and Certification of Prototype Device 
System characterization: The s-IOT prototype system will be characterized using 
phantoms following our previously established procedure (20). X-ray collimation, which 
is essential for safety and reducing the imaging dose, will be evaluated. The dose at the 
patient position will be measured using a calibrated solid-state dosimeter to insure FDA 
compliance.  The geometry calibration procedure will be evaluated against an 
established method(24). Quantitative image quality evaluation will be performed. Key 
system performance parameters including the system modulation transfer function 
(MTF), artifacts spread function (ASF), contrast to noise ratio (CNR) and signal 
differential to noise ratio (SdNR) will be measured (25, 26). Imaging time and 
consistency will be evaluated. The custom-made iterative reconstruction software will be 
evaluated against commercial reconstruction software.  All the facilities needed for this 
study are available in the PI’s lab. 
Certification: The system will be installed in the UNC-School of Dentistry (SOD) 
Radiology Clinic. Product safety testing and certification will be performed by MET 
Laboratories (www.metlabs.com), which we have previously engaged for two other x-
ray imaging systems (27).   We will work with the UNC EHS to ensure the system 
satisfies radiation safety requirement. SOD has committed the space for this study.  

 
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3.2. SPECIFIC AIM 2: Clinical Evaluation and Patient Experience 
Patient selection and image acquisition: Fifty patients referred to the UNC Section of 
Oral and Maxillofacial Radiology for bitewing or full-mouth series exams will be recruited 
following completion of their ordered radiographic exams.  Patients with moderate 
caries will be approached about participation in the study. Consenting patients will then 
receive a 4-bitewing exam using the s-IOT system. We will acquire both the ordered 
conventional radiographic exam and the s-IOT exam. The same group of patients will 
be tested for both caries detection evaluation and patient care experience.  
Caries detection: Three UNC SOD dentists will be recruited to independently review 
each radiographic exam to diagnose caries presence/absence. Discrepancies between 
reviewers will be reconciled by consensus.  
Verification: In vivo assessment of the true state of a proximal tooth surface is 
challenging. For the purpose of this study, cases where a proximal tooth surface 
received a caries diagnosis on the s-IOT images and not on the conventional images, or 
vice versa, are of particular interest. For these cases, the patient’s clinician will be 
contacted to perform reversible mild clinical tooth separation to allow visual assessment 
of caries status.  
Data analysis: The goal of the data analysis is to test (1) whether differences in the 
caries detection rate between s-IOT and conventional radiographs are present and (2), 
if so, whether these differences result from s-IOT being more sensitive. With 50 patients 
x 4 images/patient x ~4 teeth/image x 2 surfaces/tooth = 1600 surfaces, we expect 
sufficient statistical power to detect diagnostic differences.  
A statistical test for paired nominal data, such as the McNemar’s test, would be used to 
test the first hypothesis while accounting for within-patient and within-tooth/image 
correlations. Sensitivity, specificity and diagnostic accuracy are calculated from the 
clinically verified cases to characterize and quantify the modalities and will be compared 
regarding the second component of the hypothesis. To obtain proper inference to 
account for complex correlations within the same patient, or the same tooth, or the 
same image, resampling approach based on bootstrapping over 50 patients will be used 
to obtain correct variances for all statistics. NC TraCS statistician (Zeng) will help 
perform the above data analysis. 

 
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Patient experience: Each subject will be given a brief survey regarding the overall 
comfort, time, and experience differences between the two imaging systems. The 
investigators will also complete a similar brief survey regarding the overall confidence in 
diagnosis, time, and the number of required radiographic re-takes. The statistical 
different between two images systems will be analyzed. 
4. RISK AND REMEDY 
Our team has considerable experience in characterizing, and certifying medical 
devices. We do not anticipate any risk in this aspect of the project. Prior to 
implementation, the Radiation Safety Committee and IRB will assess this study. There 
is minimal risk to participants, investigators, and study personnel. The radiation dose 
from the s-IOT exam is comparable to the dose from the conventional 2D bitewing 
exam, dictating that the additional radiation burden to the patient represents no greater 
than minimal risk and technically does not require review and approval by the RSC (5 or 
fewer dental x-rays). Given the high patient volume at the UNC SOD, we do not 
anticipate problems with patient availability and recruitment. The sampling, 1600 distinct 
teeth surfaces, is substantially larger than what we have previously used for similar 
studies, and should provide sufficient statistical power to detect the diagnostic 
differences. 
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