Coherence Imaging of the Cervical Epithelium
Phase: NA
Conditions: Cervical Epithelia
Sponsor: Duke University

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Coherence Imaging of the Cervical Epithelium 
 
NCT02903394 
 
Document Date: 17 March 2017 
 

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Coherence Imaging of the Cervical Epithelium 
Duke PI: Adam Wax  
   
 
 
DUHS IRB# Pro00070555 
Jacobi site PI: Michael Zinaman 
 
 
Einstein IRB#: 2016-6643 
 
Purpose of the Study  
The purpose of this study is to develop a multiplexed low coherence interferometry (mLCI) 
endoscopic probe for mapping the epithelial types of the cervix.  This vaginal mLCI probe 
will obtain optical measurements from the cervix.  These measurements can be used to 
create a map of the surface cells that distinguishes ectocervical epithelia, endocervical 
epithelia, and the squamocolumnar junction (t-zone) between them, which is the region 
where cervical dysplasia is most likely to occur.     
 
The research study described here will be a preliminary study to evaluate the performance 
of the mLCI device for detection of cervical dysplasia.  The results from a small study at 
Duke will help to optimize the function of the mLCI instrument before completing a larger 
study with collaborators at Jacobi Medical Center (see Background & Significance below).    
The device will be studied in a larger subject population at Jacobi to determine how 
effectively it can distinguish the types of cervical epithelia. 
 
Background & Significance 
Clinical problem: Cervical cancer, caused by persistent human papillomavirus (HPV) 
infection, is the second most common female malignancy worldwide. An estimated 
500,000 new cases are diagnosed annually, including 12,170 new cases in the U.S in 
2012, which reflects an age-adjusted incidence of 8.1 per 100,000 women [1].  Given that 
cervical cancer typically develops over many years, the early detection of cervical 
dysplasia (pre-cancers) affords a critical opportunity for treatment and thus prevention of 
life threatening invasive cancer. In developed countries, the availability of cervical cytology 
(Papanicolaou smear) for routine screening and colposcopy-directed biopsy for diagnosis 
has led to decreases in incidence and mortality rates [2]. However, despite their important 
impact, cytology and colposcopy remain very limited in their sensitivity, specificity, and 
interobserver reproducibility [3, 4]. The accurate identification of dysplastic areas of the 
epithelium is challenging and hence clinical guidelines recommend frequent patient 
screening schedules [5, 6] that are particularly difficult to implement in developing 
countries. The need for more effective evaluation tools persists. 
 
Potential Solution: We propose to address this need by creating an imaging platform 
that uses coherence imaging to evaluate cervical tissues at two length scales. At the 
millimeter (tissue) scale, a multiplexed LCI (mLCI) approach will use multiple imaging 
channels to efficiently map the cervical epithelium to identify histological structures and 
red-flag suspicious regions, likely to harbor dysplasia. We have shown that mLCI can 
survey large areas of tissues in the female reproductive tract to obtain diagnostic 
information on coating by drug delivery gels [7, 8].  Once mLCI identifies suspicious areas, 
angle-resolved LCI (a/LCI) will obtain high resolution, depth resolved nuclear morphology 
measurements on the micron (subcellular) scale [9, 10].  We have shown that a/LCI can 
detect dysplastic lesions in vivo in the esophagus [11] and ex vivo in other types of 
epithelia such as colon [12] and trachea [13].  The combination of these two optical 
technologies, mLCI and a/LCI, will provide a unique platform for comprehensive 
assessment of the cervix at both tissue and subcellular scales. The novel technology will 
impact clinical detection of cervical dysplasia as well as support clinical and translational 
research on the fundamental biology of the cervical epithelium. 
 

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Rationale for collaborative project: The Duke team has had significant success in 
developing endoscopic imaging modalities for detection of precancerous tissues. Ongoing 
collaboration between the group in Duke BME and the Department of Ob/Gyn at Duke 
University Medical Center (DUMC) has produced important studies of the pharmacology 
of anti-HIV microbicides delivered to the lower female reproductive tract [7, 8, 14-17].  Here 
we seek to forge a broader collaboration to bring together the established team at Duke 
with a leading group in clinical research at Jacobi Medical Center.  Jacobi serves a 
predominately minority population, and due to the largely immigrant status of women over 
age 26, HPV vaccination rates are low.  Therefore, it has a large population of women with 
HPV-associated cervical dysplasia and a significant number of women with cervical 
cancer.   
 
This collaboration will create a powerful combination of technology development and 
translation at the leading edge of gynecological biomedicine. This project will develop and 
test new instruments for cervical imaging at Duke and field test these technologies in the 
large, diverse patient population available at Jacobi Medical Center. The anticipated 
outcome is the creation of a diagnostic imaging tool that can screen women for cervical 
precancers and cancers and/or triage precancerous lesions in women who have had a 
positive cytology test.  
 
INNOVATION 
Novel multimodal imaging platform that combines mLCI and a/LCI: The mLCI 
technology is unique in its ability for depth resolved imaging of wide areas of tissues. While 
LCI can obtain high resolution tomographic images at micron scales, as is done in optical 
coherence tomography (OCT), that approach is limited by often cumbersome scanning 
mechanisms and the large volume of data generated. Instead, mLCI uses sparse sampling 
and multiple parallel channels to more efficiently scan wider tissue areas. We will exploit 
this ability to create a new modality for quickly mapping the cervical epithelium, analogous 
to the function of colposcopy, but with improved performance. This is a particular 
challenge due to the complex combination of cervical epithelial types that are often in 
transitional states (columnar to metaplastic to squamous). As a counterpart to the mLCI, 
the a/LCI modality will combine the depth resolution and penetration of OCT with the 
sensitivity to subcellular structure that is obtained via light scattering, providing a function 
analogous to biopsy. Our group has recently validated a/LCI as an in vivo method for 
identifying dysplastic esophageal tissues [11].  Although prior research has applied OCT 
and light scattering to cervical dysplasia [18, 19] these approaches have not been clinically 
feasible. The unique capabilities of a/LCI, which enable high accuracy in detecting 
dysplasia, offer a significant potential for clinical translation. By combining mLCI and a/LCI 
into a single integrated platform, we will capitalize on recent trends in multimodal imaging. 
As identified by clinicians and researchers in multiple fields [20, 21], optimal screening 
methods can be realized by using a wide area scan to survey for suspicious regions in 
tandem with a high resolution modality to further diagnose those regions. Thus, we will 
implement this paradigm and create a hybrid imaging modality that integrates tissue and 
cellular imaging data. The unique power of this multimodal LCI device will lie in its ability 
to accurately identify dysplastic and cancerous tissues against the background of the 
complex tissue types that comprise the cervical epithelium. 
 
Innovation in clinical care of cervical disease: In the clinic, the clear advantage of the 
multimodal LCI platform will be its ability to support clinical decision-making without relying 
on gross clinical colposcopic impression, the traditional but somewhat subjective 
diagnostic method. Further, the potential to provide reliable “real-time” information to the 
clinician would allow immediate treatment of epithelial abnormalities. We expect this 

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device to be uniquely applicable to women of all ages in contrast to the recent 
implementation of screening biomarkers such as HPV DNA testing which are restricted to 
older women. Our field trials will access the diverse patient population found at Jacobi 
OB/GYN. This population represents the full spectrum of cervical health, including healthy 
young women and those with incident HPV infection, persistent HPV infection, benign 
cervical lesions, cervical precancers, and cancer. Our proposal to develop an accurate 
and efficient tool for cervical cancer screening will rely on its ability to detect disease in 
the setting of complex tissue compositions inherent to the cervix—the downfall of many 
prior optical technology attempts. Innovation is inherently risky; however our combined 
expertise in coherence imaging and the clinical study of the cervical epithelium will support 
the success of the proposal. 
 
Multi-site Study: Responsibilities 
Dr. Wax, the Duke PI of this study, is the primary awardee of the NIH grant supporting this 
work.  Dr. Wax and his team have developed the mLCI research device and will conduct 
a small study at Duke (described below) to assess if any adjustments to the device are 
needed before it is sent to Jacobi Medical Center for the larger study.  The study at Jacobi 
Medical Center will be funded as a subaward / consortium agreement of Dr. Wax’s NIH 
grant.  The research proposed in this study protocol addresses Specific Aim 1 of the NIH 
grant. 
 
Duke will recruit up to 15 women to enroll in this study, in order to achieve the target 
number of 10 subjects who complete the study at that site.  Jacobi will enroll up to 100 
women for this study, in order to achieve the target number of 40 women who complete 
the study at that site.  Data from both sites will be analyzed at Duke.  Data received from 
Jacobi will be de-identified before being sent to Duke.  Study conduct at Duke will be under 
the oversight of the IRB of the Duke University Health System.  Study conduct at Jacobi 
Medical Center will be under the oversight of the IRB of the Albert Einstein College of 
Medicine and Montefiore Medical Center.   
 
Design & Procedures 
mLCI instrument 
The purpose of this instrument is to obtain optical measurements from the cervix via a 
vaginal probe to create a map of the surface cells that distinguishes the ectocervical and 
endocervical epithelia.  The boundary between the two cell types is known as the 
squamocolumnar junction, or “t-zone”, which is the transitional region at which cervical 
dysplasia is most likely to occur. 
 
The instrument delivers infrared light to 36 locations on the cervix, and measures the 
depth-profile of back-scattered light from each location using low coherence 
interferometry (LCI).  This technique is thus termed multiplexed LCI (mLCI).  The LCI 
profile data is stored by a computer for subsequent analysis to identify cell type. 
 
The components of the mLCI instrument are grouped in the following modules: 1) 
Optical probe, 2) mLCI interferometer, 3) white light imaging module, 4) computer, and 
5) physical enclosure. 
Optical Probe 
The optical probe is primarily cylindrical in form, with a diameter of approximately 25 mm 
and a rigid length of approximately 270 mm.  The probe housing is fabricated by a 3D 
printing process known as fused deposition modeling (FDM).  The material is MED-610 
(Stratasys Inc., Eden Prairie, MN), a transparent polymer certified as biocompatible.  

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The adhesives used on the external seams of the probe are Silastic Medical Adhesive 
Type A (Dow Corning, Midland, MI), a soft silicone adhesive.  A 36-channel single-mode 
fiber bundle is contained within the probe housing, as well as several glass optical 
elements for imaging.  The rounded tip of the probe is intended to contact the cervical 
surface, and the focus of mLCI imaging is located on the plane of this tip. 
 
The probe also contains fiber optics that deliver white LED illumination to the region of 
imaging and collects wide-field imaging information through a fiber bundle to provide 
real-time video endoscopic guidance for probe placement. 
 
A flexible tether containing the 36-fiber bundle and white light optical fibers protrudes 
from the proximal end of the probe and is connected to the mLCI interferometer and 
white light imaging modules, respectively. 
 
The full length of the probe is not intended for vaginal insertion.  A demarcation line 
approximately 220 mm from the probe tip indicates the line beyond which the probe 
should not be inserted. High-level disinfection procedures as described in this document 
will be performed up to the line. 
 
The probe contains no electrical components or wires. 
mLCI interferometer 
The centerpiece of LCI instrumentation is an interferometer, in which light from a known 
reference distance is combined with light returning from the probe.  In our multiplexed 
design, 6 channels are simultaneously illuminated and interfered with each of 6 
independent references.  The mLCI thus contains 6 complete fiber optic interferometers, 
and fiber-optic switches redirect the optical inputs and outputs to progress through the 
36 channels in a sequence of 6 acquisitions. 
 
The 6 interferometers in the mLCI system are connected individually to each of 6 parallel 
fiber-optic spectrometers (Avantes, Broomfield, CO), which interface with the computer 
via one common USB connection.   
 
The light source from the mLCI system is a superluminescent diode (Superlum, Moscow, 
Russia) emitting infrared light at wavelengths between 815 and 845 nm.  The total output 
power of the SLD at its output aperture is less than 25 mW, but the amount of power 
delivered by the probe is far less.  The power at each of the individual 36 foci at the 
probe output is less than 500 µW (0.5 mW). 
 
The maximum permissible exposure (MPE) for exposures greater than 10 seconds on 
skin is 3.6 mW/mm2 at our principal wavelength of 830 nm (ANSI Z136.1).  In our 
system, only 6 channels are simultaneously illuminated.  Our imaging region in the 
tissue is 16 mm (defined by the length of our row of 6 spots) x 3.5 mm (defined by the 
minimum limiting aperture given in ANSI Z136.1) = 56 mm2. Our total permissible power 
is thus 3.6 mW/mm2 x 56 mm2 = 201 mW.  The totality of our 6 foci = 6 x 0.5 mW = 3 
mW, which is far short of the ANSI MPE. 
White light imaging module 
A white light imaging module is configured to provide video endoscopy guidance for the 
probe placement on the cervix.  This module consists of a white light LED optically 
coupled to an illumination fiber that is enclosed in the probe, as well as an imaging 

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camera and relay optics to digitize the endoscopic image from the probe’s white light 
fiber bundle. 
Computer 
A laptop computer (Lenovo, Beijing, China) performs the data acquisition and control 
through a custom application in Labview (National Instruments, Austin, TX).  Real-time 
display of the white-light endoscopic images is provided, as well as synchronized 
acquisition of LCI data from spectrometers.  Through a customized microcontroller 
module, this software also implements control of reference mirror positions by stepper 
motor and control of fiber-optic switch positions. 
Physical enclosure 
The mLCI interferometer, white light imaging module, and computer are situated upon a 
wheeled steel cart.  The fiber-optic interferometer components are protected by a metal 
enclosure.  Power to all components is provided through standard 120V mains routed 
through an uninterruptible power supply (UPS), which allows temporary disconnection of 
AC power for system transportation or due to accidental action without interrupting the 
operating state of the mLCI system. 
 
Study Procedures for subjects at Duke 
Each subject will attend 1 study visit that will last between 1 – 1.5 hours and include the 
following procedures. 
 
• 
Read consent form 
• 
Ask / answer questions 
• 
Sign consent form 
• 
Complete brief medical questionnaire to determine eligibility 
• 
Urine pregnancy test – must be negative before imaging can occur 
• 
mLCI examination of the cervix (without speculum) 
• 
mLCI examination of the cervix (with speculum) 
   
We will obtain written informed consent and confirm eligibility criteria.  Data collection will 
include a brief medical history and pregnancy testing.  Participants will be interviewed one-
on-one to complete the questionnaire regarding medical and reproductive history.  The 
nurse or doctor will then perform the mLCI study measurements.   
 
The nurse or doctor will gently place the mLCI probe against the cervix.  Lubricant will be 
placed on the outside of the probe for subject comfort.  White light camera visualization, 
incorporated into the mLCI probe, will guide the probe positioning by the clinician to 
confirm contact with the cervical epithelium.  Up to 4 minutes will be allotted for probe 
manipulation for optimal contact.  The probe will then be held in place for mLCI data 
acquisition for up to 1 minute.  When data collection is completed, or permitted time is 
elapsed, the mLCI probe will be removed and placed on a custom holder that prevents 
the contact portions of the probe from coming into contact with contaminating surfaces. 
 
The nurse or doctor will then insert a speculum in order to directly visualize the cervix.  
The mLCI probe will again be placed against the cervix with 4 minutes allotted for probe 
manipulation and 1 minute for mLCI measurements. 
 
If manipulation of the probe with the aid of a speculum does not allow satisfactory 
placement on the cervix for mLCI imaging within the permitted time, an additional attempt 
may be made with an alternate speculum, such as a Pedersen Open-Sided speculum, if 

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the medical practitioner performing the procedure believes the alternate speculum to be 
more likely to result in correct probe placement.  If the alternate speculum is used, then 
an additional 4 minutes will be allotted for probe manipulation with the alternate speculum, 
and 1 minute for mLCI measurements.  The timing of each phase of the procedure is 
summarized in the following table. 
 
Table 1: Maximum allotted times of mLCI probe insertion 
Insertion 
method 
Criteria  
Time for 
probe 
placement 
Time for 
mLCI 
acquisition 
Maximum 
total time 
Without 
speculum 
All patients 
4 min 
1 min 
5 min 
With 
standard 
speculum 
All patients 
4 min 
1 min 
5 min 
With 
alternate 
speculum 
Optional (only if standard speculum not 
satisfactory AND practitioner believes 
alternate may achieve better result) 
4 min 
1 min 
5 min 
Comparing measurements made by inserting the mLCI device with and without a 
speculum will allow us to determine if the white light visualization by the camera is 
sufficient to correctly place the probe over the cervix without having to use a speculum in 
future studies.  The ability to use an alternate in the event that a conventional speculum 
does not permit adequate mLCI probe placement will also inform our selection of the type 
of speculum, if any,that is most suited for subsequent studies. 
 
Study Procedures for subjects at Jacobi 
Subjects will be informed of the study when they present to the clinic for a regular clinical 
care visit.  If interested in participating, subjects will complete the following study-related 
procedures in addition to the standard of care visit procedures. 
 
• 
Read consent form 
• 
Ask / answer questions 
• 
Sign consent form 
• 
Urine pregnancy test – must be negative before imaging can occur 
• 
Colpophotography of cervix to compare with mLCI data 
• 
mLCI examination of the cervix (with speculum) 
   
We will obtain written informed consent and confirm eligibility criteria.  Data collection will 
include a brief medical history and pregnancy testing.   
 
The doctor will then insert a speculum in order to directly visualize the cervix.  
Colpophotographs will be taken to compare to mLCI data during data analysis.  The doctor 
will then gently place the mLCI probe against the cervix.  White light camera visualization, 
incorporated into the mLCI probe, will guide the probe positioning by the clinician to 
confirm contact with the cervical epithelium.  The probe will then be held in place for mLCI 
data acquisition for up to 1 minute.  When data collection is completed, the mLCI probe 
will be removed and placed on a custom holder that prevents the contact portions of the 
probe from coming into contact with contaminating surfaces. 
 
The doctor will then continue with the rest of the patient’s standard of care visit procedures. 
 

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At some visits, the physician may choose to make an additional measurement with the 
mLCI device, by inserting it without a speculum and using the white light camera 
(incorporated into the mLCI probe) for visual guidance to position the probe.  Comparing 
measurements made by inserting the mLCI device with and without a speculum will allow 
us to determine if the white light visualization by the camera is sufficient to correctly place 
the probe over the cervix without having to use a speculum in future studies.   
 
Selection of Subjects at Duke 
This project will recruit healthy women who: 
• 
are able to provide informed consent 
• 
are at least 21 years old 
• 
are willing to abstain from sexual intercourse for at least 24 hours before the 
study visit 
 
Participants meeting any of the following exclusion criteria will be excluded from taking 
part in this study.  Women must not: 
• 
be pregnant 
• 
have given birth to a baby 
• 
have a current gynecologic infection or discharge 
• 
be using an IUD 
• 
have had any cervical surgery 
• 
have had medical or cosmetic surgery involving the reproductive organs or 
genitals within the past 6 months 
• 
be currently enrolled in any research studies involving the application of vaginal 
formulations 
• 
be employed or supervised by the study investigators 
• 
have any other condition that, in the opinion of the study clinician, would 
contraindicate participation in the study 
 
Selection of Subjects at Jacobi 
We do not have any role in selection of the research subjects at Jacobi: this is the 
responsibility of that site. 
 
Subject Recruitment & Compensation at Duke 
We will recruit up to 15 women to enroll in this study, in order to achieve the target number 
of 10 subjects who complete the study.   
 
The study will be advertised on the ResearchMatch website. Recruiting will be managed 
by our study coordinator. The inclusion of minorities in the group of women recruited will 
reflect the local distribution in the Durham area.   
 
After learning about the study, prospective subjects will call the study coordinator for 
more information.  During this telephone call, the study coordinator will state the study 
requirements plus a brief description of the procedures. If the prospective subject is 
interested in participating in the study, a study visit will be scheduled.  The prospective 
subject’s contact information will be kept in a locked desk or file cabinet or password 
protected file in the study coordinator’s office.  If the prospective subject states that she 
does not qualify or is not interested in participating, the contact information will be 
destroyed. 
 
Subjects will be compensated $50 per visit (1 visit per subject). 

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Subject Recruitment & Compensation at Jacobi 
We do not have any role in recruiting or compensating research subjects at Jacobi: this is 
the responsibility of that site. 
 
Consent Process at Duke 
The consent process will be conducted by the study coordinator at a meeting in the 
study coordinator’s office or other suitable private location (PI’s office, conference room, 
clinic consult room).   
 
Thirty minutes will be allocated for conducting the initial consent discussion, allowing 
time for the prospective subject to read the consent form and ask any questions she may 
have.  At the consenting interview, the study coordinator will: 
• 
explain the study procedures in detail, including risks and compensation 
• 
inform the participant of her rights as a research subject, including the right to 
withdraw at any time 
• 
give the participant a chance to ask any questions she may have  
 
The prospective subject may then sign and date the consent form if she chooses to 
participate at that time.  She may take more time to consider her decision and sign the 
consent form at a later date if she chooses.  The prospective subject will have as much 
time as she needs to decide whether or not to participate.  However, enrollment will 
continue, and if all study slots are full by the time the prospective subject decides to 
participate, she may not be enrolled in the study.  Once the consent form is read and 
signed, the subject and study coordinator will complete the Informed Consent Review 
Check Sheet to document the consent process.   
 
The prospective subject will then complete a brief screening questionnaire and a urine 
pregnancy test.  Results from the screening questionnaire and pregnancy test will be 
reviewed to determine if the subject is eligible to continue participation in the study.  If 
the screening test indicates pregnancy, the participant will be excused from the study 
and advised to follow up with her physician.  Subjects who pass screening will be 
enrolled in the study on a first-come, first-served basis. 
 
The prospective subject may ask questions at any time by calling the study coordinator 
or PI.  The study coordinator will conduct all consent discussions and study visits and 
will be available to answer any questions that arise at those times. 
 
To minimize the possibility of coercion or undue influence, study personnel will inform 
subjects of their rights as a research participant, including their right to refuse to 
participate or to withdraw from the study at any time without penalty.  Reimbursement 
($50 per session) is not believed to be coercive, based on the time required and the 
nature of the research. The amount of reimbursement is comparable to similar studies.  
Duke students and employees under direct supervision of the study staff will not be 
allowed to participate in this study. 
 
Since recruiting materials (website postings) are in written English, it is expected that 
anyone who calls to inquire about participating in the study will be able to read English.  
No provisions are in place for potential participants who do not understand English.  
 
 
 

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Consent Process at Jacobi 
We do not have any role in consenting subjects at Jacobi: this is the responsibility of that 
site. 
 
Subject’s Capacity to Give Legally Effective Consent at Duke 
Subjects who do not have the capacity to give legally effective consent will not be included 
in this study. 
 
Subject’s Capacity to Give Legally Effective Consent at Jacobi 
We do not have any role in assessing subjects’ capacity to give legally informed consent 
at Jacobi: this is the responsibility of that site. 
 
Study Interventions 
See above. 
 
Risk/Benefit Assessment of the study in general 
Potential Risks 
Potential risks include: 
1. breach of confidentiality 
2. coercion 
3. discomfort with the nature of the research 
4. side effect from study procedures and/or devices 
 
Potential Benefits 
There is no direct benefit to subjects participating in this research study.  However, the 
novel mLCI device to be developed in this proposal would potentially advance the 
management of cervical dysplasia by assisting clinical decision-making without relying on 
gross colposcopic impression. The current proposal is to conduct the early feasibility 
studies necessary for technology development. Data will also be collected about epithelial 
characteristics as visualized by mLCI, which could improve our understanding about the 
basic biology of the cervical epithelium. The long-term goal is to develop devices that could 
be incorporated into routine clinical care. The mLCI device could provide real-time 
information to the clinician and reduce the number of clinical visits needed. 
 
Alternative Treatments 
There are no alternative treatments to participating in this research.  It is not intended to 
be therapeutic, but to acquire basic scientific knowledge.   
 
Risk Assessment and Risk Minimization for Study Activities at Duke 
Potential Risks 
Potential risks include: 
(1) breach of confidentiality 
(2) coercion 
(3) discomfort with the nature of the research 
(4) side effects from study procedures and/or devices 
 
Breach of Confidentiality 
Subjects will provide personal information, including sexual history and health 
information.  Breach of confidentiality will be avoided by training research staff in the 
protection of human subjects and by coding and limiting access to data.  Each 
participant will be assigned a research subject number.  The only documents linking the 

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subject’s identity with her subject number will be the consent form and the enrollment 
log.  The contact information list and payment request forms will contain the subject’s 
identity only.  The medical questionnaire, pregnancy test result, and data spreadsheets 
will reference the subject number only.  The subject’s social security number, required 
on the payment request form, will be blacked out once payment has been processed.  
Once the study is complete, all contact information will be deleted, unless the participant 
requests to be contacted for future studies conducted by Dr. Wax or his colleagues.  All 
of the participant’s study documents will be kept in a locked file cabinet in the study 
coordinator’s office.  Databases containing PHI will be maintained on a password-
protected computer with full disk encryption. 
 
Coercion 
Coercion occurs when potential participants feel compelled to participate in research for 
reasons such as perceived demand or the availability of large sums of reimbursement.  
This can be particularly true when there is little benefit to the individual for their 
participation.  In this study, there is minimal risk of coercion as personnel will inform 
subjects of their rights as a research participant, including their right to refuse to 
participate or to withdraw from the study at any time without penalty.  Reimbursement 
($50) is not believed to be coercive, based on the time required and the nature of the 
research. The amount of reimbursement is comparable to similar studies.   
   
Discomfort with the Nature of the Research 
Participants may feel discomfort with the personal nature of this research.  Before the 
participant is enrolled in the study, detailed study procedures will be explained so she is 
aware of what the research entails.  Subjects will provide personal information, such as 
sexual health and history.  Some study procedures will be conducted with the 
physician/nurse and research assistant/chaperone in the room, including insertion of the 
mLCI device into the vagina by the physician/nurse (similar to a pelvic exam) and making 
measurements with the device.  Participating in these research procedures and providing 
personal information may be uncomfortable for some women.  It is unlikely this discomfort 
will result in any serious adverse events. Should participants report discomfort with the 
research, they will be reminded of their rights to not participate in the study or to withdraw 
from the study at any time.  Subjects may contact the principal investigator or one of the 
study physicians at any time to discuss questions or concerns about the study.   
 
Side Effects from Study Procedures and/or Devices  
Risks of the mLCI Device:  The mLCI device will be handled gently for placement against 
cervical tissue.  We expect very minimal risk for tissue abrasion or irritation as the 
devices will have a smooth plastic and silicone surface and commercial gynecological 
lubricant will be applied before cervical contact. The device will be cleaned in full 
accordance with high level disinfection clinical procedures at DUHS.  Specifically, probes 
will be enclosed in a Trophon EPR high-level disinfection system to disinfect all external 
surfaces. Study staff will complete training and competency reviews per institutional 
procedures.  For the mLCI technique, a fiber optic bundle transmits near infrared light 
onto the epithelia to image the cervix.  The light source has been either certified for 
medical use or tested to demonstrate that it complies with medical safety standards.   
 
Costs to the Subject at Duke 
There will be no costs to the subject as a result of participating in this study. 
 
 

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12 
Data Analysis & Statistical Considerations 
Data analysis for Duke site 
The proposed study is designed as a pilot study, intended to provide feasibility and 
usability data to inform future studies on a larger scale. The planned pilot study will include 
10 subjects, which will yield success/failure metrics of the probe design with 10% 
precision. Elements of the probe performance that will be evaluated include ease of use 
by the medical practitioner, patient comfort, ability to access the relevant anatomy, and 
quality of mLCI imaging data.  Because the goal of the pilot study is the evaluation of 
general feasibility, no subject data will be excluded if no predetermined exclusion criteria 
are met. 
 
Data analysis for Jacobi site 
Construction of epithelium maps by mLCI: Maps of the cervix delineating the T-zone will 
be created from each subject’s mLCI data.  The extent of columnar and squamous 
epithelia will be reported as a percentage of the image of the epithelium.  Each scan in 
the 36 point field will initially be reviewed manually to determine the epithelium type based 
on the depth-resolved reflection profile for that point.  The presence of clear histological 
layers in indicative of squamous epithelium while a thinner layer with less structure 
indicates columnar epithelium [22].  As we compile a database of mLCI maps of the cervix, 
we will develop automated algorithms for assessing epithelial types and transitions by 
using cluster analysis to discriminate scans.  The mLCI maps will be compared to digital 
colpophotography analysis to assess accuracy.   
 
Measurement of epithelial areas by colpophotography: Digital colpophotographs will be 
viewed in Adobe Photoshop for quantitative computerized planimetry as previously 
published [23, 24].  We will manually outline all areas of columnar, metaplastic and 
squamous epithelia and the total visible cervical face. Total pixel counts of the various 
epithelial types will be calculated and ectopy expressed as percentage of the total cervix.  
 
Correlation of mLCI images to colpophotographs and detailed written maps: The mLCI 
epithelial maps will be visually compared to colpophotographs to achieve co-registration. 
This is feasible based on the relatively modest number of patients in the study. The written 
map and white light imaging via the probe will aid in coregistration. We will correlate mLCI 
readings with calculated areas of epithelial types (pixel counts and percentage). 
Biostatistical analyses will address covariates including age, infections, cytology, 
menstrual cycle, and sexual behaviors.  
 
Potential problems, alternative strategies, and benchmarks for success: The mLCI 
approach will be viewed as successful if there is less than average absolute difference of 
10% in the area estimate compared with manual analysis. 
  
Data & Safety Monitoring 
Reporting of Adverse Events 
An adverse event is defined as any untoward medical occurrence in a clinical research 
subject participating in the clinical study of the mLCI device.  Any AE that occurs between 
the time a study participant signs the informed consent form and the time she departs the 
study at the end of the imaging session will be captured and recorded.  Study participants 
will be instructed to contact the study site staff to report any AEs they may experience 
after completion of their participation. AE resolution will consist of evaluating instrument 
design and application to assess the potential source and implementing design changes 

Version 1.3, version date 17 March 2017 
 
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to mitigate the risk of further AE.  If necessary, AEs will be reported to the IRB according 
to IRB guidelines. 
 
Safety Monitoring 
During the proposed trial of the mLCI device, weekly status reports will be submitted to 
the Duke PI from the Jacobi site.  These reports will include all adverse events reported 
for the study, determined to be related or unrelated to the study protocol.  The study team 
will meet, as needed, throughout the period of study to review any reported adverse events 
and address any potential safety concerns.   
 
Data accuracy and protocol compliance 
Data acquired during the clinical study will be reviewed on a weekly basis by Duke lab 
personnel to assess if the data appear to be consistent with expected operating 
characteristics of the device.  In the event that data do not appear satisfactory, a review 
of protocol compliance will be conducted.  If the protocol has been followed, a technical 
inspection of the device by Duke lab personnel will be scheduled and further study will be 
suspended until instrument function has been verified.   
 
Privacy, Data Storage & Confidentiality at Duke 
The investigator will ensure that the subject’s anonymity is maintained.  Subjects will not 
be identified in any publicly released reports of this study.  All records will be kept 
confidential to the extent provided by federal, state and local law.   The study monitors 
and other authorized representatives of the Sponsor may inspect all documents and 
records required to be maintained by the Investigator, including but not limited to, 
medical records.  The investigator will inform the subjects that the above-named 
representatives will review their study-related records without violating the confidentiality 
of the subjects. All laboratory results, evaluation forms, reports, and other records that 
leave the site will be identified only by a coded number in order to maintain subject 
confidentiality.  Clinical information will not be released without written permission of the 
subject, except as necessary for monitoring by the IRB, the FDA, the NIH, the OHRP, or 
the sponsor’s designee. 
Due to the personal nature of this research, all subject interviews will take place in a 
private office and all study visits will take place in a private clinic room.  Some study 
procedures will be conducted with the physician/nurse and research assistant/chaperone 
in the room, including insertion of the LCI device into the vagina by the physician/nurse 
(similar to a pelvic exam) and making measurements with the device.  The subject will 
be draped with a sheet during these study procedures to provide as much privacy as 
possible.  
 
Subjects will provide personal information, including sexual history and health information.  
All study personnel will complete training in the conduct of human subjects research in 
order to protect against possible breach of confidentiality.  Identifiers will be removed from 
any data being analyzed.  Each participant will be assigned a research subject number.  
The only documents linking the subject’s identity with her subject number will be the 
consent form and the enrollment log.  The contact information list and payment request 
forms will contain the subject’s identity only.  The medical questionnaire, pregnancy test 
result, and data spreadsheets will reference the subject number only.  The subject’s social 
security number, required on the payment request form, will be blacked out once payment 
has been processed.  Once the study is complete, all contact information will be deleted 
or destroyed, unless the participant requests to be contacted for future studies conducted 
by Dr. Wax or his colleagues. 

Version 1.3, version date 17 March 2017 
 
14 
 
All of the paper study documents will be kept in a locked file cabinet in the study 
coordinator’s office.  Electronic study records will be maintained on a password-protected 
computer with whole disk encryption in the study coordinator’s office.  To protect against 
the possibility of loss of research records, database files will be periodically backed up to 
a DUHS network drive.   
 
 
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