Tactile Breast Imaging Sensor for Tumor Malignancy Characterization
Conditions: Breast Cancer
Sponsor: Temple University

INVESTIGATOR PROTOCOL TEMPLATE FOR MEDICAL STUDIES 
Revised: Sept. 11, 2017 
 
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Template Revision: May 27, 2019 
1) Abstract of the study 
The project is a collaboration between Dr. Chang-Hee Won of department of 
electrical and computer engineering, Dr. Dina Caroline of radiology and Dr. Kathleen 
Reilly of surgery.  Dr. Won and his colleagues have developed a tactile imaging 
sensor designed to display and quantify the touch sensation to discriminate between 
normal and abnormal tissues.  Breast tumor detection is the first application for which 
the sensor will be tested.  The goal is to develop a simple, inexpensive tool ideally to 
be used as an aid to diagnostic device in underserved communities. 
 
2) Protocol Title 
Tactile Breast Imaging Sensor  
 
3) IRB Review History 
This protocol has been reviewed once by the Temple IRB and 
modifications were required. 
4) Investigator 
Dina Caroline, MD, PhD 
5) Objectives 
The main objective of this study is to image the known tumor and compare the results 
with mammography or ultrasound.   
 
6) Background 
 
Compression-induced tactile images represent a relatively new and untapped resource in 
cancer imaging. The technology may be utilized to provide comprehensive mechanical 
and spectral information about a lesion or a tumor. This information can be used to 
develop algorithms to discriminate between malignant and benign lesions. Separately, 
elasticity imaging (Krouskop 1998; Hall 2003; Regini 2010) is actively being researched 
for breast cancer applications. However, a compression-induced tactile imaging sensor 
that addresses mechanical signatures has not yet been fully investigated.  Compression of 
the tissues from the surface by an imaging probe may change certain properties of a 
lesion such as size and shape; and this information as well as data regarding other 
mechanical properties including elasticity will be collected and analyzed.  Spot 
compression will be used to significantly increase the depth of interrogation. All these 
mechanical properties of the tumor will be analyzed and correlated with results from 
histopathological exams. We propose to develop Tactile Breast Imaging Sensor to 
characterize mechanical properties of spontaneous canine mammary tumors. 
 
Preliminary Data: We have already developed a prototype tactile sensor for tumor 
detection (Lee 2011c, Won 2011). The phantom study indicates that we can detect 
embedded inclusion size with 4.09% error, depth with 7.55% error (Lee Won 2010), and 
elasticity with 5.38% error (Lee Won 2011b, Lee 2011c, Lee Won 2013).   

INVESTIGATOR PROTOCOL TEMPLATE FOR MEDICAL STUDIES 
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1. Hall, T., (2003), “Beyond the Basics: Elasticity Imaging with US,” Radio Graphics, 
Vol. 23, No. 6, pp.1657-1671. 
2. Krouskop, T., Wheeler T., Kallel F., Garra B., (1998) “Elastic Moduli of Breast and 
Prostate Tissues Under Compression,” Ultrasonic Imaging, Vol. 20, pp. 260-274. 
3. 
Lee Jong-Ha, Chang-Hee Won. (2011a). “Tactile Elasticity Imaging Sensor and 
Non-rigid Pattern Matching Algorithm,” IEEE Sensors Journal, published on the web 
28 January 2011, Vol. 11, No. 9, ISSN: 1530-437X,  September 2011, pp. 2084-2093. 
4. 
Lee, Jong-Ha and C.-H. Won, (2011b) “Topology Preserving Relaxation Labeling 
for Non-rigid Point Matching,” IEEE Transactions on Pattern Analysis and Machine 
Intelligence, Vol. 33, No. 2, February 2011, pp.427-432. 
5. 
Lee J.H., Nathalia Garcia-Acosta, Kenny Te, and Won C.H., (2011c)“Tactile 
Sensation Imaging System for Inclusion Mechanical Property Characterization,” 
Proceeding of SPIE, BiOS, SPIE Photonics West, 22-27 January, San Francisco, 
California, USA, Volume 7890, pp. 78901D-1 to 78901D-15. 
6. 
 Lee,J.-H., Chang-Hee Won. (2013). “Tactile Sensation Imaging System for 
Embedded Lesion Characterization,” IEEE Journal of Biomedical and Health 
Informatics, Vol. 17, No. 2, ISSN 2168-2194, pp. 452-458. 
7. Regini, E., Bagnera S., Tota D., Capanino P., Luparia A., Barisone F., Durando M., 
Mariscotti G., Gandini G., (2010) “Role of sonoelastography in characterizing breast 
nodules. Preliminary experience with 120 lesions,” Radiol. Med. (La Radiologia. 
Medica.) Springer. February 22, 2010. 
 
 
Description of the Device 
The Tactile Breast Imaging Sensor operates on the principle of total internal reflection 
of light inside the soft and transparent silicone waveguide. Fig. 1(a) shows the conceptual 
diagram of the light scattering and the schematics of the system design. Fig. 1(b) shows 
the design of the current sensor.  
The sensor prototype utilizes one layer of polydimethyl siloxane (PDMS) optical 
waveguide with dimensions of 20 mm × 23 mm × 14 mm and stiffness of 27.16 ± 0.57 
kPa. We use CCD camera (Guppy F-038, Allied Vision Technologies, Exton, PA) with 
pixel size of 8.4 µm × 9.8 µm. The tactile image resolution is 768 pixels × 492 pixels. We 
attach the external force gauge (Mark-10 Series 3, Mark-10, Long Island, NY) on the top 
of device to measure the applied force and to ensure the accurateness of the tactile 
algorithm calculations. The range of the possibly measured force is from 0 to 50 N with 
the resolution of 1.0 × 10−3 N. The current sensor prototype has the 1 kΩ potentiometer 
with a digital-turning knob to control brightness of the four LEDs (4 × 1500 mcd).  These 
are commercially available LEDs, which are known to have no harmful effect on 
humans.  The output is a JPEG digital image.  The tactile images are typical JPEG 
images, which we analyze using a commercial software such as MATLAB. 

INVESTIGATOR PROTOCOL TEMPLATE FOR MEDICAL STUDIES 
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Figure 1.  (a) The sensing principle is based on total internal reflection.  (b)  The 
schematic of the tactile breast imaging sensor. The output is an image as shown 
on the laptop screen. 
 
7) Setting of the Human Research 
The research will recruit and perform procedures at Temple University 
Hospital.  We do not have a community advisory board.  No research 
procedure will be performed outside of Temple University Hospital. 
 
8) Resources Available to Conduct the Human Research
Temple University Hospital conducts over 100 breast biopsies each year.  
We will recruit less than 20 of those patients over a period of one year.  
Approximately 5% of the investigator’s time will be required to recruit 
and enroll subjects into the study, and conduct the study procedure.  All 
study personnel have been trained on and passed the protection of human 
subjects certification required by  Temple University.  The investigator 
has experience in conduct of clinical trials and have over twenty years of 
treating patients at Temple University Hospital.   
The facilities are located at 3401 N. Broad Street Philadelphia PA 19140.  
The procedure in noninvasive and it will be conducted in one visit.  
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INVESTIGATOR PROTOCOL TEMPLATE FOR MEDICAL STUDIES 
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Medical doctor will perform the procedure at the Temple University 
Hospital.  If any medical assistance is needed, the medical doctor will be 
available.  
 
9) Prior Approvals 
No other approvals are necessary. This is a non-invasive, minimal 
risk procedure that can be performed in one visit. 
 
10) 
Study Design 
a) Recruitment Methods 
Subjects will be recruited from the breast surgery clinic on a weekly basis 
until the required number of subjects has been enrolled.  We will provide 
the consent form to the patient.  No advertised will be used.  No payment 
will be made to the subject. 
 
b) Inclusion and Exclusion Criteria 
 
Inclusion Criteria: 
• Women who had mammogram and/or ultrasound Birads (category IV or V) 
• Women ages between 30 and 80.  
• Women who have been scheduled for biopsy from the Temple breast surgery 
clinic 
• Women who have been scheduled for biopsy by Dr. Kathleen Reilly. 
• Women, who speak and understand English. 
 
 
Exclusion Criteria:   
• Women who do not meet the criteria requiring biopsy. 
• Women who have allergic reaction to silicone. 
• Women who cannot speak or understand English.   
• Women who are pregnant. 
• Women, younger than 30 years old, and older than 80 years old. 
 
c) Local Number of Subjects 
Less than 20 subjects will be enrolled. 
 
 
d) Study-Wide Number of Subjects 

INVESTIGATOR PROTOCOL TEMPLATE FOR MEDICAL STUDIES 
Revised: Sept. 11, 2017 
 
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NA 
 
e) Study Timelines 
The subject will participate during one visit before biopsy.  The study will remain 
open for one year.  The preliminary analysis will be completed by December of 
2016. 
 
f) Study Endpoints 
 
The study will end in one year.  There are no secondary study endpoints. 
 
g) Procedures Involved in the Human Research 
 
Procedure:   
The patient should have had mammography or ultrasound by the time of this procedure.  
Once the doctor decides to perform biopsy, the tactile imaging will be planned. The 
breast scan, mammography, ultrasound, and biopsy are standard of care. The consent will 
be obtained before the biopsy.  One of the investigators (Dr. Caroline or Dr. Reilly) will 
obtain the consent.  Before the biopsy, the doctor will identify the mass(es) using other 
modalities such as an ultrasound. The tactile imaging sensor operator will obtain the 
tactile images.  Then the biopsy will be performed.  Radiology doctor, resident, and 
radiology technologist are always present during the procedure.  In addition a 
professional assistant from the engineering group will operate the tactile imaging sensor.  
That person will not have any physical contact with the patient.  The procedure will be 
very similar to the ultrasound device and it will be as follows: 
• The patients will be lying on their back. 
• The doctor will locate the mass using other modality (ultrasound or mammogram) 
• The tactile imaging sensor will press the part of the breast where mass are located. 
• An assistant will sketch the locations of the masses with the mass number. 
• An assistant will operate the laptop to take image of the mass.  
• The mass number will be noted with the images. 
• The tactile imaging sensor will manually compress the mass with different force 
gently.   
• The image will be taken and the mass number will be recorded. 
• This procedure will be repeated until all the masses are imaged.  
• This will take less than three minutes per mass. 

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• After the tactile images are taken the doctor will perform the biopsy of the 
masses. 
• The assistant will note the mass number and the order of the biopsy. 
• The patient will receive standard biopsy results and a letter from the doctor. 
 
Only one visit will be required for this study.  
NOTE:  
• None of the procedures done for research purposes involve radiation. 
• The use or disclosure of protected health information involves no more than a 
minimal risk to the privacy of individuals. A unique subject identifier will be 
assigned to each subject. The subjects name and date of birth will be associated 
with the identifier and will be kept on a list and stored electronically in a secure 
password protected computer under the control of the Principal Investigator. 
• Data will be kept on a password-protected computer; data is only recorded 
electronically. Data will be saved on a secure server.  
• Once the data is recorded and verified for accuracy and completeness the link to 
the patient identifier will be destroyed.  
h) Data and Specimen Banking 
No specimens will be bank for this study. 
 
i) Data Management  
 
In this project we will collect the tactile data of the tumors 
 
Standards that Would Be Applied for Format and Metadata Content: 
We will use standard formats to the data that are being stored.  Tactile spectral data will 
be stored in Excel “.xls” or “.xlsx” formats.    Matlab source codes will be stored in “.m” 
or “.c/cpp” formats.  Computer algorithm results will be stored in “.dat” or “.fig” formats.  
Technical report and papers will be either in Word format. 
 
Provisions for Keeping Data Secure: 
Experimental data, algorithm results, source codes, reports, and paper will be kept on a 
server in the CSNAP laboratory in the electrical and computer engineering department at 
Temple University.  The data will be encrypted and password protected.  All the patient 
identifiers will be removed from the spreadsheets. 
 
Data will be stored locally for no less than 6 years or as required by law. 
 
j) Confidentiality 
Data will be stored in a secure and password protected computer.  Only 
study team members, the Temple University IRB, the FDA or their 
designated representatives will have access to the data.  The study 

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investigators or team members will receive/transmit the data via secure 
compute system used by the university.  No specimens will be transported. 
 
k) Provisions to Monitor the Data to Ensure the Safety of 
subjects 
NA. 
l) Withdrawal of Subjects 
NA 
11) 
Risks to Subjects 
 
The device is not a significant risk because the device involves optical means and: 
• The device is NOT intended as an implant that presents a potential for serious 
risk to the health, safety, or welfare of a subject 
• The device is NOT purported or represented to be for a use in supporting or 
sustaining human life that presents a potential for serious risk to the health, 
safety, or welfare of a subject 
• The device is NOT for a use of substantial importance in diagnosing, 
curing, mitigating, or treating disease, or otherwise preventing 
impairment of human health that presents a potential for serious risk to 
the health, safety, or welfare of a subject  
• The device does NOT otherwise present a potential for serious risk to the 
health, safety, or welfare of a subject (Required for abbreviated IDE 
determination.) 
 
Risks and Discomforts:   
The sensor device uses an LED light source (similar to a LED flashlight).  The 
sensing probe part is made out of silicone gel. There may be minor discomfort 
resulting from the sensor pressing on breast tissues.  An allergic reaction to the 
silicone, which is the part that will be touching the tissues, is possible but uncommon.  
Currently, we are not aware of any side effects of this device. 
The tactile imaging sensor will not affect patient management. It will take less than 
three minutes to image each mass.  There are no risks beyond usual activities of daily 
living.  However, we will label all devices with the prominent sticker stating the 
following:  “CAUTION-Investigational device. Limited by Federal law to 
investigational use.”  
 
The investigator will comply with the requirements of 21 CFR §812.46 with respect 
to monitoring investigations. 
• Securing compliance. If the investigator discovers that a co-investigator is not 

INVESTIGATOR PROTOCOL TEMPLATE FOR MEDICAL STUDIES 
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complying with the signed agreement, the investigational plan, the requirements 
of this part or other applicable FDA regulations, or any conditions of approval 
imposed by the reviewing IRB or FDA will promptly either secure compliance, 
or discontinue use of the device by the co-investigator and terminate the co-
investigator's participation in the investigation. The investigator will also require 
such a co-investigator to dispose of or return the device, unless this action 
would jeopardize the rights, safety, or welfare of a subject. 
• Unanticipated adverse device effects. 
• The investigator will immediately conduct an evaluation of any unanticipated 
adverse device effect. 
• If the investigator determines that an unanticipated adverse device effect presents 
an unreasonable risk to subjects, the investigator will terminate all 
investigations or parts of investigations presenting that risk as soon as possible. 
Termination shall occur not later than 5 working days after the investigator 
makes this determination and not later than 15 working   days after the 
investigator first received notice of the effect. 
• The investigator may not resume a terminated investigation without IRB 
approval. 
 
The investigator will maintain the following records required under 21 CFR §812.140: 
• Records of each subject's case history and exposure to the device. Case 
histories include the case report forms and supporting data including, for 
example, signed and dated consent forms and medical records including, for 
example, progress notes of the physician, the individual's hospital chart(s), 
and the nurses' notes. Such records shall include documents evidencing 
informed consent and, for any use of a device by the investigator without 
informed consent, any written concurrence of a licensed physician and a brief 
description of the circumstances justifying the failure to obtain informed 
consent. The case history for each individual shall document that informed 
consent was obtained prior to participation in the study. 
• The protocol, with documents showing the dates of and reasons for each 
deviation from the protocol. . (Required for abbreviated IDE determination.) 
 
 
The investigator will make the following reports required under 21 CFR §812.150: 
• Unanticipated adverse device effects. The investigator will submit to the sponsor 
and to the reviewing IRB a report of any unanticipated adverse device effect 
occurring during an investigation as soon as possible, but in no event later than 

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10 working days after the investigator first learns of the effect. 
• Withdrawal of IRB approval. The investigator will report to the sponsor, 
within 5 working days, a withdrawal of approval by the reviewing IRB of 
the investigator's part of an investigation. 
• Withdrawal of FDA approval. The investigator will notify the IRB and 
participating investigators of any withdrawal of FDA approval of the 
investigation, and shall do so within 5 working days after receipt of notice of 
the withdrawal of approval. 
• Informed consent. If an investigator uses a device without obtaining informed 
consent, the investigator will report such use to the sponsor and the reviewing 
IRB within 5 working days after the use occurs.  (Required for abbreviated 
IDE determination.) 
• Progress reports. At regular intervals, and at least yearly, The investigator will 
submit progress reports to the IRB. 
• Recall and device disposition. The investigator will notify FDA and all 
reviewing IRB's of any request that an investigator return, repair, or otherwise 
dispose of any units of a device. Such notice will occur within 30 working 
days after the request is made and shall state why the request was made. 
• Final report. The investigator will submit a final report to the IRB within 6 
months after termination or completion. (Required for abbreviated IDE 
determination.) 
 
The investigator will not: 
• Promote or test market the device, until after FDA has approved the device for 
commercial distribution. 
• Commercialize the device by charging the subjects or investigators for a 
device a price larger than that necessary to recover costs of manufacture, 
research, development, and handling. 
• Unduly prolong the investigation. 
• Represent that the device is safe or effective for the 
purposes for which it is being investigated. (Required for 
abbreviated IDE determination.) 
 
The device will not be used for diagnosis or treatment. 
 
The data will be periodically monitored by the investigator to ensure that there are no 
new risks. 
 
 
12) 
Potential Benefits to Subjects 

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No direct benefit. 
 
13) 
Privacy and Confidentiality 
Subjects name will not be used. 
 
14) 
Compensation for Research-Related Injury 
The research involves no more than minimal risk to subjects, and there is 
no compensation available. 
 
15) 
Economic Burden to Subjects 
All research procedures will be done free of charge to the patients. 
 
16) 
Consent Process 
After patient received mammography or ultrasound,  once the doctor 
decides to perform biopsy, the tactile imaging will be planned.  The 
consent will be obtained before the biopsy.  One of the investigators (Dr. 
Caroline) will obtain the consent.  The consent will take place at the 
Temple University Hospital.  This process may take about 10 minutes.  
The patient will have an option not to participate in the study. 
 
“HRP-090 SOP: Informed Consent Process for Research” will be followed 
to obtain informed consent. 
 
Non-English Speaking Subjects 
No none-English speaking patients will be recruited into the study. 
The subjects must understand English. 
Subjects who are not yet adults (infants, children, teenagers) 
No infants, children, or teenagers will be recruited into the study. 
Cognitively Impaired Adults  
No Cognitively Impaired Adults will be recruited into the study. 
Adults Unable to Consent 
No Adults unable to consent will be recruited into the study. 

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17) 
Special considerations when obtaining consent for 
genetic studies  
No genetic studies will be conducted during this study 
 
18) 
Process to Document Consent in Writing 
All subjects will sign a written informed consent document. A signed 
and dated copy of the consent form will be given to each subject 
enrolled into the study. 
“HRP-091 SOP: Written Documentation of Informed Consent” will be 
followed to document informed consent in writing. 
 
19) 
Vulnerable Populations 
None of the populations listed below will be recruited into the study 
• Adults unable to consent 
• Individuals who are not yet adults (infants, children, teenagers) 
• Pregnant women 
• Prisoners 
20) 
Drugs or Devices 
Only authorized investigators associated with the study will use the 
imaging sensor. When not in use, the sensor and associated equipment will 
be stored in a secure lock area in the Investigators office. 
21) 
Multi-Site Human Research 
This is a single-site study  
Results of the study will not be shared with the subjects. 
 
22) 
   Statistical Data Analysis Plan 
 
We will obtain 20 tactile image data sets from the breast tumor patients.  The tactile 
images will be converted to size and deformation index.  Then these two parameters will 
be converted to risk score, which is compared against pathology results.  This is a small 
number of patients for statistically significance study.  Therefore, we plan to use the 
Leave-One-Out-Cross-Validation (LOOCV) technique to validate the human test 
results to determine the performance of the device.  
 
We obtain the Risk Score.  Risk Score is a unit less numerical value, which can be 
used as a scale to classify the tumor as malignant and benign. Based on the 
calculated size of the tumor and measured deformation index, the breast tumors are 
classified as benign and malignant using scoring method. The risk score will range 

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from 0 to 5, where 0 represents the benign and 5 represents the malignant tumor. A 
marginal threshold value was set, where any risk score below threshold is 
considered benign. The calculated risk score is based on the below equation, 
,
max
2
max
1
R
DI
DI
W
S
S
W
Score
Risk
⎥
⎦
⎤
⎢
⎣
⎡
⎟⎟
⎠
⎞
⎜⎜
⎝
⎛
×
−
×
=
             
where, W1 and W2 are the two weights used for size and deformation index 
respectively, S represents the estimated size value, Smax is the maximum estimated 
size value, DI is the calculated deformation index, DImax  is the maximum calculated 
deformation index. R is the range of risk score used.  
 
Comparing the Risk Score and the Pathology reports we obtain the following measures.  
The sensitivity, specificity and accuracy of the system have to be measured to know 
the reliability of the device. These system performance parameters helps to evaluate 
the performance of device, which is calculated based on the Risk Score using the 
below equations, 
( ),
%
FN
TP
TP
CISS
y
Sensitivit
+
=
                                      
( ),
%
FP
TN
TN
CISS
y
Specificit
+
=
                  
( ).
%
FN
TP
FP
TN
TP
TN
CISS
Accuracy
+
+
+
+
=
 
 
The positive result shows the presence of malignant tumor whereas the negative 
result implies the presence of benign tumor. TP, TN, FP, and FN represent true 
positive, true negative, false positive and false negative cases respectively. False 
positive is considered to be a case where benign masses are classified as malignant, 
whereas false negative are cases where malignant masses are classified as benign. 
True positives are the correctly classified malignant cases. True negatives are the 
correctly classified as benign cases.