A Clinical Trial to Evaluate the Effectiveness and Safety of Dual Energy Cone-Beam Computed Tomography (DE-CBCT) Imaging for Quantitative Measurement of Jaw Bone Density
Phase: NA
Conditions: Dental Diseases
Sponsor: University of California, Los Angeles

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A clinical trial to evaluate the effectiveness and safety of Dual Energy Cone Beam 
Computed Tomography (DE-CBCT) imaging for quantitative measurement of jaw bone 
density 
 
Protocol Version: November 16, 2020 
NCT04686084 
 
 
 

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Protocol Number: 
IRB#20-001768 
Version Date: 
16 November 2020 
Investigational Product: 
Dual-energy Cone Beam Computed Tomography Unit, RCT720 
Sponsor: 
Ray Co. Ltd 
 
Funding Organization: 
Seoul National University 
Seoul, S. Korea 
Principal Investigator: 
Name: Sanjay M. Mallya, BDS, MDS, PhD 
 
Telephone: 
(310) 825-1689 
Fax: 
 
(310) 825-7232 
E-mail:  
smallya@dentistry.ucla.edu 
Medical Monitor: 
Name: Kyungyoon Kang, CEO, MSA, RAC 
 
Telephone: 
812 345 7485 
Fax: 
 
 
E-mail: Kyungyoon.kang@kbiotechsolutions.com 
 
Coordinating Center: 
If applicable 
 
This confidential information about an investigational product is provided for the exclusive use of 
investigators of this product and is subject to recall at any time.  The information in this document 
may not be disclosed unless federal or state law or regulations require such disclosure.  Subject to the 
foregoing, this information may be disclosed only to those persons involved in the study who have a 
need to know, with the obligation not to further disseminate this information.   
 
PROTOCOL AGREEMENT 
 
I have read the protocol specified below. In my formal capacity as Investigator, my duties include 
ensuring the safety of the study subjects enrolled under my supervision and providing the project’s 
sponsors with complete and timely information, as outlined in the protocol.  It is understood that all 
information pertaining to the study will be held strictly confidential and that this confidentiality 
requirement applies to all study staff at this site. Furthermore, on behalf of the study staff and myself, I 
agree to maintain the procedures required to carry out the study in accordance with accepted GCP 
principles and to abide by the terms of this protocol. 
 
Protocol Number:  IRB#20-001768 
 
Protocol Title:  A clinical trial to evaluate the effectiveness and safety of Dual Energy Cone 
Beam Computed Tomography (DE-CBCT) imaging for assessment of jaw bone density 
 
 
Protocol Date:  
 
 
 
 
Investigator Signature  
 
Date 

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Print Name and Title 
Site Name 
UCLA School of Dentistry 
Address 
10833 Le Conte Ave 
 
Los Angeles, CA 90095-1668 
 
 
Phone Number 
310 825 1689 
 
 
 
 

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PERSONNEL AND RESPONSIBIITIES 
 
Sanjay M Mallya, BDS, MDS, PhD, Principal Investigator 
Dr. Mallya will serve as the PI of this project. He will be the primary contact person for all administrative 
and research issues related to this project. He will coordinate with the UCLA School of Dentistry 
Research Office and/or the UCLA Office of Intellectual Property and Industry Sponsored Research for 
proposal submission and post award processing. He will co-ordinate preparation and submission of all 
documentation needed for Institutional Review Board review and approval of this project and ensure 
that all procedures are carried out as per institutional guidelines for human subjects research. He will 
coordinate with the UCLA School of Dentistry Finance Office on all post-award budgetary management 
of this contract. He will assume primary responsibility for the planning and execution of the proposed 
image analyses. He will coordinate with the Information Technology support staff to design and 
implement the appropriate data management and storage plans. He will coordinate with the staff 
research associate to implement procedures for timely submission of results to project sponsors as 
required. 
 
Tara Aghaloo, DDS, PhD, Co-Investigator 
Dr. Aghaloo will serve as a co-investigator on this project. She will participate in the design, execution 
and analyses of the data as described in this proposal. She will coordinate with the CRC for this study for 
patient recruitment, as appropriate. As needed, she may participate in administrative aspects of this 
proposal, as described above. 
 
Sotirios Tetradis, DDS, PhD, Co-Investigator 
Dr. Tetradis will serve as a co-investigator on this project. He will participate in the design, execution and 
analyses of the data as described in this proposal. As needed, he may participate in administrative 
aspects of this proposal, as described above. 
 
Reuben Kim, DDS, PhD, Co-Investigator 
Dr. Kim will serve as a co-investigator on this project. He will participate in the design, execution and 
analyses of the data as described in this proposal. As needed, he may participate in administrative 
aspects of this proposal, as described above. 
 
 
Staff Research Associate, To Be Hired 
The SRA will provide support to Principal- and Co-investigators on all administrative aspects of this 
study, including IRB preparation and submission, coordination with project sponsors and collaborators, 
documentation of informed consent, maintenance of research data, collation of results and 
coordination within the research group meetings and with collaborators to ensure appropriate project 
advancement. 
 
 

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STATEMENT OF COMPLIANCE 
 
This trial will be carried out in accordance with International Conference on Harmonization Good Clinical 
Practice (ICH GCP) and the following: United States (US) Code of Federal Regulations (CFR) applicable to 
clinical studies (45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, and 21 CFR Part 812). 
 
The protocol, informed consent forms, recruitment materials, and all participant materials will be 
submitted to the UCLA Institutional Review Board (IRB) for review and approval obtained before any 
participant is enrolled.  Any amendment to the protocol will be submitted to the UCLA IRB for review 
and approval before the changes are implemented to the study.  In addition, all changes to the consent 
form will be IRB-approved; a determination will be made regarding whether a new consent needs to be 
obtained from participants who provided consent, using a previously approved consent form. 
 
 
 

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TABLE OF CONTENTS 
 
1 
PROTOCOL SUMMARY .................................................................................................................................. 9 
1.1 
SYNOPSIS ............................................................................................................................................................ 9 
1.2 
SCHEMA ........................................................................................................................................................... 12 
1.3 
SCHEDULE OF ACTIVITIES ...................................................................................................................................... 13 
2 
INTRODUCTION .......................................................................................................................................... 14 
2.1 
STUDY RATIONALE .............................................................................................................................................. 14 
2.2 
BACKGROUND AND SIGNIFICANCE .......................................................................................................................... 14 
2.3 
RISK-BENEFIT ASSESSMENT .................................................................................................................................. 16 
2.3.1 
Known potential risks ........................................................................................................................... 16 
2.3.2 
Known potential benefits ..................................................................................................................... 17 
2.3.3 
Risk-benefit assessment ....................................................................................................................... 17 
3 
OBJECTIVES AND ENDPOINTS ..................................................................................................................... 17 
3.1 
PRIMARY OBJECTIVE ............................................................................................................................................ 17 
3.2 
SECONDARY OBJECTIVE ........................................................................................................................................ 17 
4 
STUDY DESIGN ............................................................................................................................................ 17 
4.1 
OVERALL DESIGN ................................................................................................................................................ 17 
4.2 
SCIENTIFIC RATIONALE ......................................................................................................................................... 18 
4.3 
BLINDING.......................................................................................................................................................... 18 
4.4 
JUSTIFICATION FOR DOSE ..................................................................................................................................... 18 
4.5 
END OF STUDY DEFINITION ................................................................................................................................... 18 
5 
STUDY POPULATION ................................................................................................................................... 18 
5.1 
RATIONALE FOR NUMBER OF SUBJECTS ................................................................................................................... 18 
5.2 
INCLUSION CRITERIA ............................................................................................................................................ 19 
5.3 
EXCLUSION CRITERIA ........................................................................................................................................... 19 
5.4 
LIFESTYLE CONSIDERATIONS .................................................................................................................................. 19 
5.5 
SCREEN FAILURES ............................................................................................................................................... 19 
5.6 
STRATEGIES FOR RECRUITMENT ............................................................................................................................. 20 
6 
STUDY INTERVENTIONS AND ADMINISTRATION ......................................................................................... 20 
6.1 
STUDY INTERVENTION ADMINISTRATION.................................................................................................................. 20 
6.1.1 
Study intervention description ............................................................................................................. 20 
6.1.2 
Administration ..................................................................................................................................... 20 
6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY ............................................................................................. 20 
6.2.1 
Acquisition and accountability ............................................................................................................. 20 
6.2.2 
Formulation, appearance, packaging, and labeling ............................................................................ 22 
6.2.3 
Product storage and stability ............................................................................................................... 26 
6.2.4 
Preparation .......................................................................................................................................... 26 
6.3 
MEASURES TO MINIMIZE BIAS ............................................................................................................................... 27 
6.4 
STUDY INTERVENTION COMPLIANCE ....................................................................................................................... 27 
6.5 
CONCOMITANT THERAPY ...................................................................................................................................... 27 
6.5.1 
Rescue medication ............................................................................................................................... 27 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT DISCONTINUATION/WITHDRAWAL ........... 28 
7.1 
DISCONTINUATION OF STUDY INTERVENTION............................................................................................................ 28 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY .............................................................................. 28 

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7.3 
LOST TO FOLLOW UP ........................................................................................................................................... 28 
8 
STUDY ASSESSMENTS AND PROCEDURES ................................................................................................... 28 
8.1 
STUDY SCHEME .................................................................................................................................................. 28 
8.2 
EFFICACY ASSESSMENTS ....................................................................................................................................... 30 
8.3 
SAFETY ASSESSMENTS .......................................................................................................................................... 30 
8.4 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS ...................................................................................................... 30 
8.4.1 
Definition of adverse event .................................................................................................................. 30 
8.4.2 
Serious adverse event .......................................................................................................................... 30 
8.4.3 
Classification of an adverse event ........................................................................................................ 30 
8.4.4 
Time Period and Frequency for Event Assessment and Follow-Up ...................................................... 31 
8.4.5 
Adverse event reporting ....................................................................................................................... 32 
8.4.6 
Serious adverse event reporting .......................................................................................................... 32 
8.4.7 
Reporting events to participants .......................................................................................................... 32 
8.4.8 
Events of special interest ..................................................................................................................... 32 
8.4.9 
Reporting of pregnancy ....................................................................................................................... 32 
9 
STATISTICAL CONSIDERATIONS ................................................................................................................... 32 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .................................................... 33 
10.1 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS ........................................................................... 33 
10.1.1 
Informed consent process ............................................................................................................... 33 
10.1.2 
Study discontinuation and closure .................................................................................................. 33 
10.1.3 
Confidentiality and Privacy ............................................................................................................. 34 
10.1.4 
Future use of stored specimens and data ....................................................................................... 34 
10.1.5 
Key roles and study governance ...................................................................................................... 34 
10.1.6 
Safety Oversight ................................................................................. Error! Bookmark not defined. 
10.1.7 
Clinical monitoring .......................................................................................................................... 35 
10.1.8 
Quality assurance and quality control ............................................... Error! Bookmark not defined. 
10.1.9 
Data handling and record keeping .................................................................................................. 35 
10.1.10 
Protocol deviations .......................................................................................................................... 35 
10.1.11 
Publication and data sharing policy ................................................................................................ 35 
10.1.12 
Conflict of interest policy ................................................................................................................. 35 
11 
BIBLIOGRAPHY............................................................................................................................................ 36 
 
 
 

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List of Abbreviations 
AE 
adverse event 
BD 
bone density 
CFR 
Code of Federal Regulations 
CRF 
case report form 
CBCT 
cone beam computed tomography 
CT 
computed tomography 
DE-CBCT 
dual-energy cone beam computed tomography 
DMC 
Data Monitoring Committee 
DSMB 
Data Safety Monitoring Board 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IRB 
Institutional Review Board 
MDCT 
multidetector computed tomography 
QC 
Quality Control 
PI 
Principal Investigator 
UADE 
Unanticipated Adverse Device Effect 
 
 

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1 PROTOCOL SUMMARY 
1.1 
Synopsis 
 
TITLE 
A clinical trial to evaluate the effectiveness and safety of Dual Energy Cone-
Beam Computed Tomography (DE-CBCT) imaging for assessment of jaw 
bone density 
SPONSOR 
Ray Co., Ltd. 
DEVICE MANUFACTURER 
Ray Co., Ltd. 
RATIONALE 
Current radiologic imaging modalities used in dentistry provide information 
on the morphology of the hard tissues. Additional information on the 
density of bone has practical relevance, for example, in dental implant 
treatment planning, where local bone quality is a known strong predictor of 
successful implant osseointegration. The Dual-Energy Cone Beam 
Computed Tomography (DE-CBCT) device is designed to overcome 
limitations of traditional imaging and will provide assessment of jaw bone 
density in additional to morphological information. 
This clinical trial will examine the application of DE-CBCT to assess jaw bone 
density and compare Hounsfield units (HU) values with multidetector CT, 
an established standard for assessing BD.  
STUDY DESIGN 
This is a single center, open-label trial, designed to enroll 24 patients. Both, 
the researcher and the subject know the treatment the participant is 
receiving. 
 
PRIMARY OBJECTIVE 
To evaluate the effectiveness and safety of DE-CBCT to evaluate jaw bone 
density and compare HU values with those of multidetector CT, an 
established standard for assessing BD. 
NUMBER OF SUBJECTS 
24 patients 
 
 

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SUBJECT SELECTION 
CRITERIA 
Inclusion Criteria: 
1. 
Patients who need x-ray imaging for dental treatment planning and/or 
diagnosis  
2. 
Males or females aged older than 21  
3. 
Can follow instructions to be positioned into the CT scanner 
4. 
Can remain physically immobile during the CT scan acquisition 
5. 
Voluntarily sign and date the informed consent 
Exclusion Criteria: 
1. Pregnancy 
2. Patients who are unable to comprehend the risks of the study to 
provide informed consent 
3. Extensive dental restorations, maxillofacial prosthesis, or orthopedic 
hardware that likely may cause artifacts and degrade quality, as 
determined by the study radiologists 
TEST DEVICE, MODEL, 
PURPOSE 
Dual Energy-Cone Beam Computed Tomography (DE-CBCT), RCT720 
CONTROL DEVICE, MODEL, 
PURPOSE 
Multidetector Computed Tomography (MDCT), 
DURATION OF SUBJECT 
PARTICIPATION AND 
DURATION OF STUDY 
Subjects will be on study for up to 30 days 
Total Study period:  12 months 
Enrollment & Follow-up:  1 month 
The total duration of the study is expected to 12 months. Once enrolled, 
the test subject will be on the study for one month including recruitment 
and final subject follow-up. 
STUDY METHOD 
The study is based on two visits (VISIT 1 and VISIT 2)  
• DAY 0 (enrollment):  
Subject is queried for inclusion/exclusion criteria and informed about the 
study. If he/she agrees to participate, inclusion/exclusion criteria and 
informed consent will be documented. An imaging stent, which bears 
radiopaque markers, will be also created for each patient.  
• VISIT 1:  
Inclusion/exclusion criteria will be reconfirmed and the DE-CBCT imaging 
will be completed. 
• VISIT 2 (no more than 30 days since the enrollment):  
Inclusion/exclusion criteria will be reconfirmed and MDCT imaging 
completed. 
- Depending on availability of scheduling on MDCT unit, Visit 2 may occur on the 
same day as Visit 1. 
Clinical Assessments 
The following assessments will be performed and recorded on Case Report 
Form:  
• 
Demographics 
• 
Any relevant medical history 
• 
Site-specific BD assessment (Region of Interest, ROI) 
• 
Adverse Events  
PRIMARY ENDPOINT 
Jaw BD (HU values) assessed by DE-CBCT and by MDCT  
SECONDARY ENDPOINT 
Agreement between the BD assessments by evaluators 

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SAFETY EVALUATIONS 
Incidence of adverse events (AE): Adverse events on the days of the study 
visits will be documented. The PI/staff evaluates the severity of AE and the 
causal relationship using ‘safety evaluation criteria.’ The PI will report the 
case to the investigator/sponsor and IRB subsequently.  
PLANNED INTERIM 
ANALYSES  
None 
STATISTICS 
Primary Analysis Plan 
• 
The correlation between DE-CBCT and MDCT HU values of bone 
density will be performed using Pearson. 
• 
The agreement between DE-CBCT and MDCT HU values of bone 
density will be performed using Bland-Altman plots.  
• 
In order to evaluate the observer reliability, Kappa statistics will be 
performed.  
Rationale for Number of 
Subjects 
The correlation coefficient of human mandibular bone density (in HU) 
between CBCT and MDCT was observed to be 0.89, according to the study 
conducted by Parsa et al. (Reference paper: Bone quality evaluation at 
dental implant site using multidetector CT, micro-CT, and cone beam CT)  
 
Using the formula below, the number of patients is calculated to be 7.  
 
n = (𝑧𝛼/2 + 𝑧𝛽
∁(𝑟0)
)
2
+ 3,
∁(𝑟0) = 1
2 ln (1 + 𝑟0
1 −𝑟0
) 
 
Since we have three age groups (7ⅹ3 = 21) and expect the dropout rate to 
be 10% (21ⅹ(1+0.1)=24), a total of 24patients will be enrolled for the 
current study.   
 
 
 

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1.2 
Schema 
 
Day 0 
PRE-STUDY 
SCREENING and 
RECRUITMENT 
 
 
• Inform patients about the study 
• Identify and screen potential subjects for inclusion and exclusion 
criteria 
• Obtain informed consent 
• Fabricate stent for enrolled patients 
 
 
 
Acceptable time frame: Day 1 to day 30 
VISIT 1 
 
 
• Acquire dual energy CBCT scan of the jaws  
 
 
 
Acceptable time frame: Day 1 to day 30 
VISIT 2* 
 
 
• Acquire MDCT scan of the jaws 
 
 
* Visit 2 shall not be more than 30 days before/after visit 1.  
* Depending on availability of scheduling on MDCT unit, Visit 2 may occur on the same day as Visit 1. 
 
 
 

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1.3 
Schedule of activities 
 
Procedures 
Screening 
Study Visit 1 
Study visit 2 
(≤30 d from visit 1) 
Allowable windows 
for visit 
Day 0 
Day 1 
Day 30  
Informed consent 
X 
X 
 
Demographics 
X 
X 
 
Medical history 
X 
X 
 
DE-CBCT 
 
X 
 
MDCT 
 
 
X 
 
 

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2 INTRODUCTION 
 
2.1 
Study Rationale 
Current imaging modalities used in dentistry include 2-dimensional radiographs, and 3-dimensional CT 
imaging. All of these x-ray-based modalities provide information on the morphology and architecture of 
the dental hard tissues and alveolar bone. Although these images display relative degrees of solidity 
within these hard tissues, they are of limited value for reliable, qualitative assessment of the bone 
density. Information on the jaw bone density has practical relevance, for example, in dental implant 
treatment planning, where local bone quality is a known strong predictor of successful implant 
osseointegration.  
The Dual-Energy Cone Beam Computed Tomography (DE-CBCT) device is designed to overcome 
limitations of traditional dental imaging and will provide assessment of jaw bone density in additional to 
morphological information. This clinical trial will examine the application of DE-CBCT to assess jaw bone 
density and compare this novel device with multidetector computed tomography (MDCT). 
 
2.2 
Background and Significance 
Computed tomography (CT) is an x-ray-based imaging technique that produces cross-sectional images 
of the body. In all CT techniques, a collimated x-ray source and a detector revolve around the patient. 
The detector records photon attenuation by assessing the number of photons that exit the patient, 
registering this information at several hundred angles through the rotational arc. Complex mathematical 
algorithms translate this attenuation data into a three-dimensional (3D) map that spatially locates the 
attenuating structures.1 
 
MDCT is the most widely used CT scanner design across the world. In MDCT, multiple rows of detectors 
are incorporated into the array in the z-axis (craniocaudal axis, patient’s head to foot), allowing capture 
of multiple image slices during each gantry revolution. Current detector spatial resolution allows 
imaging of submillimeter dimensions. Volumetric acquisition with isotropic imaging allows reformatting 
in planes different from the axial acquisition, without compromising image quality. Contemporary MDCT 
scanners have 64 to 128 rows of detectors, with some vendors manufacturing scanners with 320 and 
640 detector rows. 
 
CBCT is an advanced imaging modality with several applications in dentomaxillofacial diagnosis and 
treatment planning.2-8 In this technique, a cone-shaped x-ray beam and a detector rotate around the 
patient acquiring multiple projections that reconstructed into a volumetric image. Depending on the 
manufacturer and protocol, detector pixel elements are in the range of 70µm to 400µm, providing high 
resolution 3D volumetric imaging.  
 
 In CT data, each voxel in the reconstructed CT volume is represented by a numerical gray value (CT 
number).1 This number reflects the degree of x-ray attenuation and represents the average linear 
attenuation coefficient of that voxel. Major factors that influence the CT number include the tissue 
features (atomic number and density) and homogeneity and energy of the x-ray beam. CT numbers are 
expressed as Hounsfield units (HU), which expresses x-ray attenuation of a voxel relative to the 
attenuation of water. In the HU scale, the CT number 
of water is defined as zero, and the CT number of air 
is defined as −1000. The HU values of ~ 200 and 
higher represent densities of trabecular and cortical 
bone.   

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CBCT and HU: Assessment of BD has relevance in dentistry. The degree of mineralization of bone at 
dental implant sites are strong determinants of implant osseointegration and stability. Likewise, closer 
representation of attenuation and CT numbers are important for third party applications of CT data that 
use automatic segmentation for computer-aided design and computer-aided manufacturing 
applications. Current dental CBCT units do not apply a standard scaling system for representing CT 
numbers, and attempts to convert CBCT numbers to HU are unsuccessful. In particular, the cone beam 
geometry of the x-ray beam produces scatter radiation and consequently decrease the signal-to-noise 
ratio, with a practical negative impact on contrast resolution of the CBCT image.1  
 
Studies from our group and others have shown that although the relationship between CBCT numbers 
and object density is linear, this relationship is influenced by several factors including imaging protocol 
and anatomic location.9-15 Collectively, these factors result in an inhomogeneity of CT numbers on CBCT 
scans. For example, the CT number of the same object differed depending on the anatomical location in 
which it was imaged.15 Specifically, the CT numbers of phantom objects were higher when placed within 
the anterior region of the jaw and lower in the posterior regions.9,15 Importantly, objects with low x-ray 
attenuation suffered greater variability than objects with high attenuation.9,15 Moreover, these CT 
numbers are markedly influenced by scanner settings.11 Due to these inconsistencies in CT numbers 
through the CBCT volume, it is not feasible to apply mathematical equations that will accurately derive 
HU through the CBCT volume. Nevertheless, there is promise to harness the power of CT imaging to 
decipher more than just morphological information. In a prior clinical study, CBCT gray values assessed 
at edentulous implant sites showed a trend of decreasing gray values with bone quality type.14   
 
Current CBCT imaging uses a poly-energetic x-ray beam, with peak energies typically in the range of 
90kVp to 110kVp. Attenuation of the x-ray photons is a function of the absorber’s atomic number and 
the energy of the incident photons, and the resultant gray value in an image pixel represents the 
magnitude of this attenuation. As described above, factors include scatter radiation and reconstruction 
algorithms impact the accuracy of the true attenuation. In DE-CBCT, attenuation data is assessed using 
two x-ray sources with different energy spectra. Following acquisition at both energies, mathematical 
algorithms are applied to compare attenuation between the two energies, and to translate this 
information into better estimates of bone mineral density. Thus, DE-CBCT provides an approach to 
assess both morphology and the chemical composition of bone. The proposed study will examine a new 
CT device, a DE-CBCT unit to provide additional valuable information on bone density, a factor that 
impacts surgical technique and successful osseointegration. 
 
Practical Applications of BD assessment in dental implant treatment planning: CBCT imaging is widely 
used to evaluate edentulous sites for potential dental implant placement. Assessment of bone quantity 
and quality at the potential implant site is an essential objective of imaging. Bone quantity refers to the 
height and width of the residual alveolar bone. Bone quality represents the thickness of cortical bone, 
the abundance of trabecular bone, and the overall degree of mineralization.14 In particular, local quality 
of bone is a key factor that influences successful osseointegration. The Lekholm and Zarb classification16 
is widely used to categorize bone quantity and quality for implant placement. This classification scheme 
continues to be used in clinical practice and is recorded as the subjective perception during drilling prior 
to implant placement. In this classification bone quality is categorized into four types:  
Type 1: Predominantly cortical bone 
Type II: Central core of dense trabecular bone surrounded by a thick layer of cortical bone 
Type III: A thin layer of cortical bone surrounding dense trabecular bone 
Type IV: A thin layer of cortical bone that surrounds low density trabecular bone 

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Another widely used assessment, the Misch classification scheme, attempts to categorize subjective 
radiologic appearance based on a range of HU.17 Similar to the Lekholm and Zarb classification, this 
scheme is a subjective assessment, and this limits the depth of practical application for reliable 
prediction of successful osseointegration. 
 
 
 
Pre-surgical assessment of bone quality is of high practical relevance. Success rates of implants placed 
implants placed in D4 have lower success rates. Modifications to surgical techniques have been devised 
to improve osseointegration of implants placed in low density bone.18 In this study, jaw bone density 
assessed by DE-CBCT will be compared with that measured on MDCT, which is the gold standard for 
measuring bone density. The ability of DE-CBCT to provide information on jaw bone density could have 
tremendous impact on case selection and positively impact outcomes. 
 
 
2.3 
Risk-Benefit Assessment 
2.3.1 
Known potential risks 
The risks from this study are related to radiation exposure. Subjects in this study will receive two x-ray 
examinations: 
(a) MDCT, Maxillofacial, without contrast, Standard treatment, CPT 70486: The MDCT exam is acquired 
as standard treatment protocol for dental treatment planning. The typical dose (Dose-area product, 
DAP) for CT examination of head is 35,000-48,000 mGy•cm2. 20 
(b) DE-CBCT, Investigational device: The radiation dose (DAP) is approximately 883 mGy•cm2. Overall, 
the doses from DE-CBCT are low to negligible. Compared with MDCT, the radiation dose from DE-
CBCT is approximately one fiftieth (2%). 
 
The radiation doses are orders of magnitude below threshold doses needed to cause deterministic 
effects. Thus, we do not expect any immediate risks from radiation exposure.  
The only potential risks of this added radiation are long-term risk of radiation induced cancer. As 
described above, the radiation doses delivered by the DE-CBCT device are several-fold lower than 
diagnostic CT scans, indicating that these risks are much lower than risks of current diagnostic imaging 
procedures.  
 

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2.3.2 
Known potential benefits 
There are no direct established health benefits from the DE-CBCT. However, the subjects’ participation 
in this study will provide essential data that could potentially improve health outcomes, that would 
eventually benefit the society at large. 
 
2.3.3 
Risk-benefit assessment 
Although participants do not benefit directly from the DE-CBCT scan, the additional risks are minimal. 
The device design, intended to deliver low doses for maxillofacial imaging, is the key method to 
minimize current risks, as well as risks to patients for potential future use. 
 
3 
OBJECTIVES AND ENDPOINTS 
3.1 
Primary objective 
To evaluate the effectiveness and safety of DE-CBCT to assess jaw bone density and compare these 
values with MDCT, an established standard for assessment of BD. 
 
3.2 
Secondary objective 
To analyze the agreement between the BD assessments by the evaluators  
 
4 
STUDY DESIGN 
4.1 
Overall design 
This study will test the hypotheses that DE-CBCT will be equivalent to MDCT to assess BD in the jaw 
bones. 
 
The study design is an open-label clinical trial to evaluate the effectiveness and accuracy of DE-CBCT to 
assess BD in jaw bones. This single center trial will enroll 24 subjects, with equal gender distribution. In 
order to investigate the HU values of bone density across the intended patient population age range, the 
patients will be recruited according to the three classified age groups. Each study subject will receive 
both the investigational DE-CBCT and the standard of care MDCT scan, which serves as the control. 
 
Age Group 
Number of Patients 
Below age 45 (≤ 45 years old) 
Male : 4      Female: 4 
Older than 45 and less than 65 (45 – 65 years old) 
Male : 4     Female: 4 
Over age 65 (≥ 65 years old) 
Male : 4      Female: 4 
 
The study-specific procedures will be completed in two visits at the UCLA Dental Center and the UCLA 
Ronald Reagan Hospital. Subjects recruited into the study are those requiring CT imaging for dental 
diagnosis or treatment planning, including but not limited to implant treatment planning, jaw bone 
pathoses, impacted teeth etc. In order to mark the ROI area, the dental surgeon will fabricate a custom 
acrylic stent worn by the patient during imaging. The stent incorporates radiopaque markers that 
indicate the location(s) and angulation(s) of the proposed ROI area.  
 
The study-specific procedures are as below: 
Screening 
Informed consent 
Study-specific process, 20-30 min 
Visit 1 
DE-CBCT (experimental scan) 
~20 min 

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Visit 2 
MDCT (Standard of care scan) 
~20 min 
 
Following scan acquisition, the study’s investigators will evaluate the CT scan and make BD assessments 
at specific locations, as directed by the radiopaque markers in the stent.  BD will be assessed in at least 
three individual sites per subject. 
 
4.2 
Scientific rationale 
The basic premise of this study is that the investigational device (DE-CBCT) will provide accurate 
estimates of BD in the dento-alveolar bone. The accuracy of DE-CBCT assessments will be determined 
against the clinical gold standard for BD assessment. The outcome of this study will demonstrate the 
efficacy and accuracy of DE-CBCT to assess BD at jaw sites. 
 
4.3 
Blinding 
Evaluators are able to distinguish DE-CBCT and MDCT by appearance and thus cannot be blinded to the 
modality. However, investigators measuring the BMD will be blinded to the measurements on the 
standard/experimental CT, and to measurements made by other investigators, until the measurement 
phase is completed. The statistician will remain blinded, until the data is locked and delivered for 
statistical analysis. 
 
4.4 
Justification for dose 
Not applicable 
 
4.5 
End of study definition 
A participant will be considered to have completed the study if he/she has completed both scheduled 
visits including the DE-CBCT and MDCT imaging. 
 
5 STUDY POPULATION 
5.1 
Rationale for Number of Subjects 
Based on the reference paper called “Bone quality evaluation at dental implant site using multislice CT, 
micro-CT, and cone beam CT,” the correlation coefficient of human mandibular bone density (HU) 
between CBCT and MDCT was observed to be 0.89. In assumption that there also exists a correlation 
between the HU values of DE-CBCT images and MDCT images, Pearson’s correlation analysis was 
considered for calculating the appropriate number of patients for the current study.  
With 0.05 Type 1 Error (significance level 5%) and 80% statistical power, the number of patients is 
calculated to be 7. Further considering the three age groups and 10% of dropout rate will result in a 
total of 24 patients to be enrolled in the study.  
 
Below is the hypothesis and calculation formula:  
 
• 
Hypothesis:  
Null hypothesis : H0 : ρ = 0,   Alternative hypothesis : H1 : ρ = 𝑟0 ≠0 
 
 
 
• 
Formula:  

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n = (
𝑧𝛼/2 + 𝑧𝛽
∁(𝑟0)
)
2
+ 3,
∁(𝑟0) = 1
2 ln (1 + 𝑟0
1 −𝑟0
) 
ln : Log to the base of e 
𝑟0 : Correlation coefficient value to be tested  
α : Type 1 error 
β : Type II error 
𝑧𝛼/2 : Value corresponding to 100(α/2)% in the standard normal distribution curve 
𝑧𝛽 : Value corresponding to 100(β)% in the standard normal distribution curve  
 
 
• 
Calculation:  
① α=0.05, 1-β=0.80 
② 𝑟0=0.89 
   n = (
𝑧𝛼/2+𝑧𝛽
∁(𝑟0) )
2
+ 3, ∁(𝑟0) =
1
2 ln (
1+𝑟0
1−𝑟0) 
                                                              = (
1.960+0.842
1.422
)
2
+ 3 = 6.88 
③ Three age groups: 7ⅹ3=21 
④ Dropout rate: 10%, n=24 
 
5.2 
Inclusion criteria 
• 
Patients who need x-ray imaging for dental diagnosis and/or treatment planning  
• 
Males or females aged older than 21   
• 
Can follow instructions to be positioned into the CT scanner 
• 
Can remain physically immobile during the CT scan acquisition 
• 
Voluntarily sign and date the informed consent 
 
5.3 
Exclusion criteria 
• 
Pregnancy 
• 
Patients who are unable to comprehend the risks of the study to provide informed consent 
• 
Extensive dental restorations, maxillofacial prosthesis, or orthopedic hardware that likely may cause 
artifacts and degrade quality, as determined by the study radiologists. 
 
5.4 
Lifestyle considerations 
Not applicable 
 
5.5 
Screen failures 
Patients who sign the informed consent will have satisfied all inclusion and exclusion criteria, and thus, it 
is unlikely that we will have screen failures. Screen failures could occur if a patient decides to revoke 
informed consent or provides additional data that changes eligibility assessment. In such cases, we will 
document relevant information including the reason for screen failure, and the specific criteria that are 
unmet. 
As per the American College of Radiology practice parameters for imaging pregnant patients19, 
diagnostic examinations of the head and neck do NOT require verification of pregnancy status, because 

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they do not directly expose the pelvic/abdominal area, and the scattered dose to the embryo/fetus is 
negligible. Nevertheless, pregnant patients are excluded from this study, following a markedly 
conservative approach to radiation safety. 
Verification of pregnancy status will be via clinical history and is often sufficient for this examination. For 
example, women may attest that they cannot reasonably be pregnant, are between regular menstrual 
periods, or are on long-term birth control. From a scientific viewpoint, uncertainty regarding pregnancy 
typically exists in the early stages. Given the low radiation doses, the likelihood of effects on the 
embryo-fetus are negligible. 
 
5.6 
 Strategies for recruitment 
• 
The study will recruit subjects who are seeking dental treatment at the UCLA Dental Center.  
• 
The target population is patients, 21 years and older.  
• 
In this study, we will aim for an approximately equal gender distribution in the three age groups.  
• 
Potential participants will be identified via the UCLA Dental Center Clinics, and participation 
opportunity will be publicized at these clinics and to relevant providers of dental treatment at the 
UCLA Dental Clinic via electronic and paper communication.  
• 
Vulnerable populations are NOT a target of this recruitment. 
• 
The subject will receive the standard of care MDCT scan at no charge, typically a $400 value. The DE-
CBCT scan will be done at no charge. 
• 
Participants will be reimbursed for parking at the UCLA School of Dentistry (Visit 1) and the UCLA 
Ronal Reagan Hospital (Visit 2), approximately $22 in value. 
• 
Because this study involves an additional visit, participants will receive financial compensation of 
$100. 
 
6 
STUDY INTERVENTIONS AND ADMINISTRATION 
6.1 
Study intervention administration 
6.1.1 
Study intervention description 
The device a Dual Energy-Cone Beam Computed Tomography (DE-CBCT), RCT720, is used to make the 
images of subjects’ dento-alveolar bone. The study’s radiologist will evaluate these images to make 
assessments of jaw bone density at specific sites.  
 
6.1.2 
Administration 
The image will be taken once, preferably on the day of the patient’s enrollment into the study. 
 
6.2 
Preparation/Handling/Storage/Accountability 
6.2.1 
Acquisition and accountability 
The investigational device is a CT scanner that will be installed by the manufacturer in the UCLA Oral 
Radiology Clinic and will be used according to the instructions. 
 
• 
Investigational Device Description  
The RCT720 is intended for 3D computed tomography for scanning hard tissues like bone and 
teeth. By rotating the C-arm which is embedded with a dual high voltage generator, all-in-one 
x-ray tube and a detector on each end, cone beam computed tomography(CBCT) images of 
dental maxillofacial are attained by recombining data from the same level that are scanned 

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from different angles. The dual energy can be used to obtain the HU value for confirming 
alveolar bone density.  
 
- Manufacturer: Ray Co., Ltd. 
- Trade Name: RCT720 
- Common Name: Dental panoramic/tomography and cephalometric x-ray system  
- Regulation Name: Computed tomography x-ray system  
- Regulation Number: 892.1750 
- Device Class: II  
 
The control device is a CT scanner that is already installed at the UCLA Ronal Reagan Hospital for the 
standard diagnosis. It will be used according to the instructions. 
 
• 
Control Device Description  
The Multi Detector Computed Tomography (MDCT) uses multiple x-ray tubes and detectors to 
produce tomographic images by recombining coplanar data obtained from different angles. 
 
- Manufacturer: To Be Established by UCLA Radiology 
- Trade Name: Multidetector Computed Tomography  
- Common Name: Whole body computerized tomography X-ray imaging device 
- Regulation Name: To Be Established by UCLA Radiology   
- Regulation Number: To Be Established by UCLA Radiology 
- Device Class: II  
 
 
 

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6.2.2 
Formulation, appearance, packaging, and labeling 
 
• 
Investigational Device (RCT720) 
- Appearance and Formulation: 
 
 
- Technical Specifications  
1) X-ray tube: 
UNo. 
ULabel 
UFunction 
(1) 
Vertical carriage 
Device which supports the rotating arm 
(2) 
CT Detector  
Part embedded with a detector used for acquiring the CT  
imaging where the X-ray penetrating the subject is received then 
converted into an electrical signal and sent to the controller. 
(3) 
X-ray generator 
Part which generates the X-ray for imaging 
(4) 
Touch Monitor 
Includes functions (height adjustment, alignment beam  
on/off, product initialization) that can control the basic  
settings for product operation 
(5) 
Handle 
Part grabbed by the patient to get in position for imaging 
(6) 
Column 
Part which adjusts the product height according to the  
patient’s height 
(7) 
Base 
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• Focal sport dimension: 0.5mm 
• Maximum tube voltage (imaging): 50~100kVp 
• Target angle: 5° 
• Inherent filtration: 0.8mm Al at 50kV 
• X-ray tube characteristic curve: 
 
 
 
 
a.  Maximum rating chart: 
 
 
b.  Emission & Filament characteristics: 
 
 
c. Anode thermal characteristics:  

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2) High Voltage Generator: 
• Power: Single phase 100-240VAC, 50/60Hz  
• Power consumption: 2.5kVA Max 
• Maximum power: 1.53kW 
• Tube voltage and tube current control range: 
Modality 
Tube Voltage 
(kV) 
Tube Current  
(mA) 
kW  
(kV x mA) 
CT 
60~90 
4 ~ 17 
(Maximum permissible tube current 
=1.12kW / set tube voltage) 
Max 1.12 
 
3) X-ray Controller (Collimator): 
Modality 
Magnification ratio 
Exposure time 
CT (Patient) 
1.44 
~14sec 
 
4) Detector:  
Modality 
Sensor type 
CT 
(FXDD-0606CA) 
Flat panel X-ray sensor 
Detector pixel size: 119㎛ 
Pixel Matrix: 1256(W) x 1256(H) 
Sensing Area : 149.5 (W)x 149.5 (H)mm 
FOV : 160mm x 100mm(Max.) 
 
5) Console PC main frame: 
• OS : Windows 10, 64Bit or higher 
• CPU : Intel Dual core or better 
• RAM : 8GB or higher 
• HDD : 1TB or higher 

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• Network: Ethernet network 
• Display: 32 bit color display or higher 
• Resolution : 1366×768 or higher 
 
6)  Column: 
• Movement range: Column stroke (max and min height difference) 670mm 
• Vertical Movement: Powered movement 
 
7) Alignment Beam (for patient positioning): 
• Laser Class(by IEC60825-1) : Class I 
• Wavelength: 650nm±20nm 
• Output : <1mW 
 
8) Software  
• Name: RayScan  
• Version: Ver 1.0 higher  
 
- Packaging and Labeling: 
• Each component of the device will be sealed in a ‘bubble wrap’ to prevent the damage 
and packaged in a cardboard box. On the surface of the box and on the main body of the 
device, the statement “CAUTION-Investigation Device. Limited by Federal Law to 
Investigational Use” will be posted. Further information on the purpose of the 
investigation, name and place of business of the manufacturer, distributor, the quantity 
of contents, and a description of all relevant contraindications, hazards, adverse effects, 
warnings, and precautions will be included in the labeling.  
 
 
 

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• 
Control Device (MDCT) 
• MDCT device already installed and in operation at UCLA Ronald Reagan Hospital. 
Routine maintenance performed as per institutional and state radiation regulatory 
agencies. 
 
6.2.3 
Product storage and stability 
• 
Investigational Device (RCT720) 
- Storage condition  
    1) Temperature range : -10 ~ 50 ℃ 
    2) Relative humidity : 10 ~ 90 % 
    3) Atmospheric pressure range : 700 ~ 1060 hPa 
 
 
6.2.4 
Preparation 
• 
Investigational Device (RCT720) 
The following is the instruction for how to use the investigational device. User manual must be 
referred for the details.  
1) Preparation  
     a. Only the trained user can operate the device.  
     b. Before using the product, the user must read the user manual.  
     c. After confirming that all cables are properly connected, connect the device to the power 
cable.  
     d. Check if the switch and the device are operating properly.  
2) Operation  
     a. Turn the power switch to “ON.”  
     b. Turn on the PC and execute ‘RayScans.’ 
     c. Click [MWL] on the upper left of the screen and [New] button on the lower right to 
register a new patient.  
     d. Select the scanning mode and set the desired values for the tube voltage and the tube 
current.  
     e. After adjusting the height of the device to a patient’s height using the remote control or 
the touch screen, press the [ready] button on the PC or touch screen.  
     f. When the irradiation switch lightens up in green, press the irradiation switch until 
scanning is completed. Release the irradiation switch, if emergency occurs.  
     g. In case of an emergency, press the [Emergency] switch located in front of the power 
switch. To restart, turn the [emergency] switch to clockwise direction, until the pressed 
power switch pops out.  
     h. When scanning is completed, save the image and exit ‘RayScans.’ 
      i. Press the power switch to “OFF” to turn off the power.  
   j. In order to reboot the device, wait 5 to 10 seconds after the device is turned off. Then, 
press the power switch to the “ON” position.  
3) Cautions 
  a. Store in a place where there is no possibility of occurrence of adverse effects due to air 
pressure, temperature, humidity, ventilation, sunlight, dust, salt, and etc.  
  b. During the use, the device and the patient must be monitored.  
c. Clean regularly with a neutral detergent and make sure the solution does not enter the 
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d. Using an antiseptic solution such as ethyl alcohol, disinfect the area directly contacted by 
the patient.  
e. The device and components must be regularly inspected. 
 
6.3 
Measures to minimize bias 
This study does not include randomization into control and treatment groups. Each subjects’ CBCT scan 
is used as the control to the investigational DE-CBCT scan. 
 
6.4 
Study intervention compliance 
Not applicable. The intervention is a CT scan, and does not require adherence beyond the imaging visit. 
 
6.5 
Concomitant therapy 
No restriction for participation in the study 
 
6.5.1 
Rescue medication 
Not applicable 
 
 

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7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
 
7.1 
Discontinuation of study intervention 
The intervention (patient imaging) occurs in one visit. The only reason to not do the patient imaging 
would be new information that changes the inclusion/exclusion. The study team will document relevant 
information including demographics, reason for discontinuance, and the specific criteria that are unmet. 
Since the study is a single imaging intervention, discontinuance from the study has no impact on the 
patient’s safety or well-being and requires no further action from the study team. 
 
7.2 
Participant Discontinuation/Withdrawal from the Study 
Participants are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue or withdraw a participant from the study for the following reasons: 
• 
Pregnancy 
• 
Significant study intervention non-compliance  
• 
Development of new conditions that would change inclusion/exclusion criteria 
• 
If the participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
• 
Participant unable to receive CT for 30 days. 
 
The reason for participant discontinuation or withdrawal from the study will be recorded on the Case 
Report Form (CRF).  
 
7.3 
Lost to follow up 
A participant will be considered lost to follow-up if he or she fails to return for one or more of the two 
study visits and is unable to be contacted by the study staff. 
The following actions must be taken if a participant fails to return to the clinic for a required study visit: 
• 
The site will attempt to contact the participant and reschedule the missed visit to the earliest 
available date, and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain if the participant wishes to and/or should continue in the study. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee will make every 
effort to regain contact with the participant (where possible, 3 telephone calls, within a 1-week 
span). These contact attempts should be documented in the participant’s study file.  
Should the participant continue to be unreachable, he or she will be considered to have withdrawn from 
the study with a primary reason of lost to follow-up. 
 
8 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
Study scheme 
Screening for eligibility  
Prior to the appointment, patients will be identified by their UCLA dental provider as potentially needing 
a CT scan of the jaws for treatment planning. The patients will be prescreened by a member of the 
research team for age eligibility. The study staff will coordinate with UCLA Dental Clinic staff to identify 
patients and meet with them during their visit. 
Patient recruiters such as dental surgeons will also be briefed on the nature of the study and the 
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screening visit, the research team will confirm eligibility via the inclusion and exclusion criteria and 
explain the risks of the study to the patients. 
 
Enrollment (Day 0) 
1. Patients that are cleared through the screening eligibility and who voluntarily sign the informed 
consent will be enrolled into the study. The patient will be cleared through the screening eligibility 
based on the inclusion and exclusion criteria. If not suitable for the enrollment, the reason will be 
recorded on the Case Report Form. 
 
2. An imaging stent will be created for the scanning. This stent, fabricated by the treatment team, bears 
radiopaque markers to provide location information on the CT scan, and typically requires lag time for 
laboratory fabrication. Patients will be scheduled for the CT scan by the research team, in 
coordination with the surgical team. 
 
Study Procedure: DE-CBCT scan (Visit 1) 
1. Patients scheduled for their imaging procedures will be confirmed by the research team via the name 
and date of birth and assigned an alphanumeric code. 
 
2. For women in childbearing age, pregnancy status will be confirmed and recorded.  
 
3. The region of interest (example: tooth number, potential implant site) that requires radiographic 
imaging will be recorded. 
 
4. DE-CBCT: Prior to imaging, the DE-CBCT unit will be calibrated using a hydroxyapatite (HA) standard 
phantom. Calibration is performed by taking the images for three times with the tube energy settings 
of 60 kV / 90 kV. The device will be calibrated three times throughout the study period- prior to the 
initiation of the study, half the number of patients are recruited, before the end of the study.  
 
⚫ The details of the HA phantom are as follows:  
- Manufacturer: QRM GmbH, Germany 
- Material: CaHP (Calcium Hydroxy Apatite) 
- HA Concentration (mg/cm3): 0, 100, 200, 400, 600, 800, 1000, 1200 
- Calibration protocol: ISO 9001 QM-System 
 
5. Following the calibration, the research staff will acquire a DE-CBCT imaging. Either mandible or 
maxilla, depending on the tooth number (imaging site), will be imaged. The appropriate imaging 
mode will be selected depending on patient size and field of view, and the tube energy set at 60 kV / 
90 kV. The DE-CBCT will be acquired with the imaging stent in place. 
 
6. Subject will be scheduled for MDCT scan (Visit 2). The next visit must be within 30days after the visit 
1. Depending on the availability of scheduling on MDCT unit, Visit 2 may occur on the same day as 
Visit 1. 
 
7. Before the patient returns home, the study staff will educate the subject to contact him/her if adverse 
events such as nausea, vomiting, hair loss, and oral inflammation occur.  
 
 
 

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Study Procedure: MDCT scan (Visit 2) 
1. Patients scheduled for their MDCT imaging procedures will be confirmed by the imaging facility via 
the name and date of birth and assigned screening number. 
2. For women in childbearing age, pregnancy status will be re-confirmed and recorded. 
3. The region of interest (example: tooth number, potential implant site) that requires radiographic 
imaging will be recorded. The imaging site for MDCT scan will be identical to the one for DE-CBCT 
scan.  
4. The patient will be imaged using the standard clinical protocol for MDCT, and simultaneous scanning 
of the calibration phantom (QRM-BDC/6). 
 
8.2 
Efficacy assessments 
BD Assessment 
In each patient’s MDCT and DE-CBCT scans, discrete regions of interest (ROIs) will be made in the area 
where radiographic imaging is necessary for the dental diagnosis and treatment plan. The ROI will be 
angulated, sized, and positioned to mark the treatment area. Using the software tools, the BD will be 
assessed and recorded. The assessments at each location will be recorded and the HU values of DE-CBCT 
will be correlated with those of MDCT. 
Assessments will be made independently by two oral and maxillofacial radiologists. Each radiologist will 
make these assessments twice, with at least one month between the two assessments. 
 
8.3 
Safety assessments 
As described, the primary risk from the DE-CBCT examination is from ionizing radiation. With the low 
dose used in this procedure, we do not anticipate any deterministic radiation-related effects. The lack of 
such events will be documented after each examination. 
 
8.4 
Adverse events and serious adverse events 
8.4.1 
Definition of adverse event 
An Adverse Event (AE) in this clinical trial includes any unfavorable and unintended signs, or symptoms 
associated with the use of DE-CBCT and CBCT, whether or not considered intervention related.  
AE may be expected (ex: symptoms related to deterministic radiation effects) or unexpected. 
Unexpected AE is a sign or symptom not identified in nature, severity, or frequency in the current 
Investigator’s Brochure or of greater severity than expected based on the information in the 
Investigator’s Brochure. 
 
8.4.2 
Serious adverse event 
An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of either the 
investigator or sponsor, it results in any of the following outcomes: death, a life-threatening adverse 
event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant 
incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital 
anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or 
require hospitalization may be considered serious when, based upon appropriate medical judgment, 
they may jeopardize the participant and may require medical or surgical intervention to prevent one of 
the outcomes listed in this definition. 
 
8.4.3 
Classification of an adverse event 
Severity of event 

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• 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities.  
• 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or incapacitating.  Of 
note, the term “severe” does not necessarily equate to “serious”. 
 
Relationship to study intervention 
All adverse events (AEs) must have their relationship to study intervention assessed by the clinician who 
examines and evaluates the participant based on temporal relationship and his/her clinical judgment. 
The degree of certainty about causality will be graded using the categories below. In a clinical trial, the 
study product must always be suspect.  
 
Related – The AE is known to occur with the study intervention, there is a reasonable possibility that the 
study intervention caused the AE, or there is a temporal relationship between the study intervention 
and event. Reasonable possibility means that there is evidence to suggest a causal relationship between 
the study intervention and the AE. 
Not Related – There is not a reasonable possibility that the administration of the study intervention 
caused the event, there is no temporal relationship between the study intervention and event onset, or 
an alternate etiology has been established. 
 
Expectedness 
The Principal investigator in collaboration with the co-Investigators will be responsible for determining 
whether an adverse event (AE) is expected or unexpected.  An AE will be considered unexpected if the 
nature, severity, or frequency of the event is not consistent with the risk information previously 
described for the study intervention. 
 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to the attention of 
study personnel during study visits and interviews of a study participant presenting for medical care, or 
upon review by a study monitor. 
 
8.4.4 
 Time Period and Frequency for Event Assessment and Follow-Up 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured on the 
appropriate case report form (CRF). Information to be collected includes event description, time of 
onset, clinician’s assessment of severity, relationship to study product (assessed only by those with the 
training and authority to make a diagnosis), and time of resolution/stabilization of the event. All AEs 
occurring while on study must be documented appropriately regardless of relationship. All AEs will be 
followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. However, if the study participant’s condition deteriorates at any 
time during the study, it will be recorded as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. AEs characterized as intermittent require documentation of 
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The PI or his designee will record all reportable events with start dates occurring any time after 
informed consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of 
study participation.  At each study visit, the investigator will inquire about the occurrence of AE/SAEs 
since the last visit.  Events will be followed for outcome information until resolution or stabilization. 
 
8.4.5 
 Adverse event reporting 
The PI/designee will record non-serious adverse events and report them to project sponsor within 30 
working days after investigator first learns of the effect. 
 
8.4.6 
 Serious adverse event reporting 
The study investigator shall complete an Unanticipated Adverse Device Effect Form and submit to the 
study sponsor and to the reviewing Institutional Review Board (IRB) as soon as possible, but in no event 
later than 10 working days after the investigator first learns of the effect.  The study sponsor is 
responsible for conducting an evaluation of an unanticipated adverse device effect and shall report the 
results of such evaluation to the Food and Drug Administration (FDA) and to all reviewing IRBs and 
participating investigators within 10 working days after the sponsor first receives notice of the effect. 
Thereafter, the sponsor shall submit such additional reports concerning the effect as FDA requests. 
 
8.4.7 
 Reporting events to participants 
Not applicable. The investigational device exposes subjects to low levels radiation and we do not 
anticipate any adverse events that require us to contact participants to ensure their health and safety.  
 
8.4.8 
 Events of special interest 
Not applicable. 
 
8.4.9 
 Reporting of pregnancy 
Not applicable. 
9 
STATISTICAL CONSIDERATIONS 
In this study, we seek to recruit 24 patients to evaluate the effectiveness and safety of DE-CBCT for 
assessing jaw bone density compared to the current clinical gold standard for BD measurement, MDCT. 
This primary objective will be analyzed by correlating DE-CBCT HU values to MDCT HU values and 
Pearson will be performed for the correlation.  The higher the correlation coefficient, the more DE-CBCT 
correlated to MDCT, meaning DE-CBCT is equivalent to the clinical use of MDCT.  
 
To evaluate the accuracy of DE-CBCT and its equivalence to MDCT, we will analyze the agreement 
between the two methods using Bland-Altman plots.  
 
To evaluate the intra- and inter-observer reliability, observer we will use Kappa statistics to: 
1. Quantify the level of agreement between duplicate assessments by the same radiologist 
2. Quantify the level of agreement between independent assessments by the two radiologists 
 
 
Evaluation analysis group 
In this clinical trial, the data from PP analysis group (Per-Protocol Analysis Set) will be analyzed.  
 

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① Per Protocol Analysis Set: 
The PP analysis group includes subjects who complete the study according to the study plan without a 
significant violation of the protocol- from voluntarily agreeing to participate in the study to finishing the 
scanning of both DE-CBCT and MDCT. If the quality of image is affected by the metal prosthesis, the 
subject corresponding to the image is excluded from the PP analysis group. 
 
② A major violation of the study plan to be excluded from the PP analysis group: 
The quality of the image, especially the area where ROI is located, is degraded by the metal prosthesis. 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 Regulatory, ethical, and study oversight considerations 
 
10.1.1 Informed consent process 
 
10.1.1.1 Consent/Assent and other informational documents provided to participants 
Consent forms describing in detail the study intervention, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting 
intervention/administering study intervention.  The following consent materials are submitted with this 
protocol: 
• 
Informed consent document. 
 
10.1.1.2 Consent Procedures and Documentation 
 Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Consent forms will be Institutional 
Review Board (IRB)-approved and the participant will be asked to read and review the document. The 
investigator will explain the research study to the participant and answer any questions that may arise. 
A verbal explanation will be provided in terms suited to the participant’s comprehension of the 
purposes, procedures, and potential risks of the study and of their rights as research participants.  
Participants will have the opportunity to carefully review the written consent form and ask questions 
prior to signing. The participants should have the opportunity to discuss the study with their family or 
surrogates or think about it prior to agreeing to participate. The participant will sign the informed 
consent document prior to any procedures being done specifically for the study. Participants must be 
informed that participation is voluntary and that they may withdraw from the study at any time, without 
prejudice. A copy of the informed consent document will be given to the participants for their records. 
The informed consent process will be conducted and documented in the source document (including the 
date), and the form signed, before the participant undergoes any study-specific procedures. The rights 
and welfare of the participants will be protected by emphasizing to them that the quality of their 
medical care will not be adversely affected if they decline to participate in this study. 
 
10.1.2 Study discontinuation and closure 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause.  Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party to <study participants, investigator, funding agency, 
the Investigational New Drug (IND) or Investigational Device Exemption (IDE) sponsor and regulatory 
authorities>.  If the study is prematurely terminated or suspended, the Principal Investigator (PI) will 
promptly inform study participants, the Institutional Review Board (IRB), and sponsor and will provide 

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the reason(s) for the termination or suspension.  Study participants will be contacted, as applicable, and 
be informed of changes to study visit schedule.  
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Demonstration of efficacy that would warrant stopping    
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination that the primary endpoint has been met 
• 
Determination of futility 
 
Study may resume once concerns about safety, protocol compliance, and data quality are addressed, 
and satisfy the sponsor, IRB and/or Food and Drug Administration (FDA). 
 
10.1.3 Confidentiality and Privacy 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their 
staff, and the sponsor(s) and their interventions. This confidentiality is extended to cover testing of 
biological samples and genetic tests in addition to the clinical information relating to participants. 
Therefore, the study protocol, documentation, data, and all other information generated will be held in 
strict confidence. No information concerning the study or the data will be released to any unauthorized 
third party without prior written approval of the sponsor.  
 
All research activities will be conducted in as private a setting as possible. 
 
The study monitor, other authorized representatives of the sponsor, representatives of the Institutional 
Review Board (IRB), regulatory agencies or pharmaceutical company supplying study product may 
inspect all documents and records required to be maintained by the investigator, including but not 
limited to, medical records (office, clinic, or hospital) and pharmacy records for the participants in this 
study. The clinical study site will permit access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by the reviewing IRB, Institutional policies, or sponsor requirements. 
 
10.1.4 Future use of stored specimens and data 
Data collected for this study will be analyzed and stored at the UCLA School of Dentistry. During the 
conduct of the study, an individual participant can choose to withdraw consent to have their CT scans 
stored for future research. However, withdrawal of consent with regard to scan data storage may not be 
possible after the study is completed. 
 
10.1.5 Key roles and study governance 
Principal Investigator 
Medical Monitor 
Sanjay M. Mallya, BDS, MDS, PhD 
Kyungyoon Kang, CEO, MSA, RAC 
UCLA School of Dentistry 
K-Biotech Incorporated 
10833 LeConte Ave 
Los Angeles, CA 90095-1668 
201 South 4th Street, Suite 727 
San Jose, CA95112 
310 825 1689 
812 345 7485 
smallya@dentistry.ucla.edu 
Kyungyoon.kang@kbiotechsolutions.com 

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10.1.6 Clinical monitoring 
Clinical monitoring is conducted to ensure that the rights and well-being of trial participants are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct of 
the trial is in compliance with the currently approved protocol/amendment(s), with International 
Conference on Harmonisation Good Clinical Practice (ICH GCP), and with applicable regulatory 
requirement(s).  
 
10.1.7 Data handling and record keeping 
10.1.7.1 Data collection and management responsibilities 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the 
principal investigator. The PI is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. 
 
All source documents will be completed in a neat, legible manner to ensure accurate interpretation of 
data.  Data recorded in the electronic case report form (eCRF) derived from source documents will be 
consistent with the data recorded on the source documents.  
 
Clinical data (including adverse events (AEs), concomitant medications, and expected adverse reactions 
data) and clinical laboratory data will be entered into a 21 CFR Part 11-compliant data capture system.  
 
10.1.7.2 Study records retention 
Study documents will be retained for a minimum of 2 years after the last approval of a marketing 
application in an International Conference on Harminosation (ICH) region and until there are no pending 
or contemplated marketing applications in an ICH region or until at least 2 years have elapsed since the 
formal discontinuation of clinical development of the study intervention. These documents may be 
retained for a longer period, however, if required by local regulations. No records will be destroyed 
without the written consent of the sponsor, if applicable. The sponsor will inform the PI when these 
documents no longer need to be retained. 
 
10.1.8 Protocol deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, International Conference on 
Harmonisation Good Clinical Practice (ICH GCP), or Manual of Procedures (MOP) requirements. The 
noncompliance may be either on the part of the participant, the investigator, or the study site staff. As a 
result of deviations, corrective actions will be developed by the site and implemented promptly.  
The study team will use continuous vigilance to identify and report deviations within 5 working days of 
identification of the protocol deviation, or within 5 working days of the scheduled protocol-required 
activity.  All deviations will be addressed in study source documents, reported to sponsor.  Protocol 
deviations will be sent to the UCLA Institutional Review Board (IRB).  
 
10.1.9 Publication and data sharing policy 
The study will follow institutional and sponsor guidelines for data sharing and publication. 
 
10.1.10 Conflict of interest policy 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical.  Therefore, any actual conflict of interest of persons who have a role in the design, 

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conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the design and conduct of this trial.  UCLA has 
established policies and procedures for all study group members to disclose all conflicts of interest and 
will establish a mechanism for the management of all reported dualities of interest. 
 
11 BIBLIOGRAPHY 
 
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