Evaluation of Breast CT
Phase: NA
Conditions: Breast Cancer
Sponsor: University of California, Davis

 
 Evaluation of Breast CT 
 
NCT00584233 
 
 
Protocol 214750 including statistical analysis plan 
 
 
 
Protocol Version dated March 1, 2021 
 

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1) 
Protocol Title 
 
Principal Investigator: John M. Boone, PhD, Professor of Radiology 
Title:  Evaluation of Breast CT 
Protocol Version Date: March 1 2021 
 
 
2) 
Objectives 
 
The purpose of this study is to evaluate the efficacy of breast computed 
tomography (CT) for breast cancer detection. A breast CT scanner has been built 
using a flat panel detector and cone beam techniques. The breast CT system will 
be evaluated to determine the efficacy of the scanner in the detection of lesions 
and the results will be compared to breast MRI, mammography and the 
histopathological findings of the detected lesions. 
 
 
We have studied the potential of breast CT (bCT) for breast imaging under an NIH-
funded Biomedical Research Partnership (BRP) grant (R01 EB002138-10), and 4 
breast CT scanners have been developed that have imaged over 600 women to 
date (under more than one IRB-approved protocol).  The BRP grant cannot be 
renewed, and with this (resubmitted) R01 grant application, we seek to finalize our 
research in breast CT – The specific aims have been significantly modified as a 
result of the first critique, and we now focus on a narrower set of remaining issues. 
 
Specific Aims: 
 
Contrast injections are used to identify breast cancer lesions in clinical procedures, 
most notably breast MRI (gadolinium contrast agent).  Other investigators have 
demonstrated the utility of iodine contrast agent injection for breast cancer 
delineation in projection mammography techniques, using both dual energy 
subtraction (Lewin) and temporal subtraction (Yaffe) to highlight the visualization 
of the breast tumor.  
 
Specific Aim 1: Develop scatter correction and image processing methods to 
improve Hounsfield Unit (HU) accuracy.   
The UC Davis bCT scanners do not use an anti-scatter grid to keep radiation dose 
low. We have developed an inverse beam stop method for accurate scatter-
correction, but this needs to be implemented in software. In addition to this 
physics-based scatter correction method, additional image processing methods 
will be explored to maximize the quantitative integrity (Hounsfield unit accuracy) 
of bCT images while minimizing cupping. We hypothesize that improvements in HU 

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accuracy will improve the quantitative predictive value of CE-bCT, for example, 
comparing differences in lesion HU before and after contrast injection (ΔHU). 
 
Specific Aim 2: Optimize non-contrast bCT imaging for microcalcification detection. 
The ultimate goal of the breast tomography project is to improve breast cancer 
screening beyond the limitations of projection mammography, and for practical 
reasons this precludes contrast injection for screening normal risk patients.  Since 
the (4th) Doheny scanner has >4 times the MTF (at 10%) than earlier scanners, we 
believe that bCT can now compete with mammography for microcalcification 
detection. In this aim, image optimization in terms of microcalcification detection 
performance will be performed. Using physical phantoms with microcalcifications, 
image reconstruction parameters (apodization filter, matrix dimensions, 
preprocessing techniques, etc.) will be optimized and evaluated using 
mathematical metrics and human observer performance studies on phantoms 
containing microcalcifications. 
 
Specific Aim 3:  Clinical Trial: Imaging women using breast CT and CE-MRI 
Women with suspicious lesions (BIRADS 4+5) will undergo digital mammography 
(“2D”) and tomosynthesis (“3D”) as standard of care workup. Patients who 
participate will undergo both unenhanced and contrast enhanced breast CT 
imaging, and also contrast-enhanced breast MRI. Both breasts (affected and 
unaffected) will be imaged  with bCT and MRI.  Our facility biopsies 2400 patients 
over 5 years, and power analysis shows that we will need a total of 400 patients 
whose images will be used for the normal-risk patient screening comparisons (Aim 
4) and for the high risk patient screening comparisons (Aim 5). 
 
Specific Aim 4:  Normal Risk Screening Performance: Comparison of non-contrast 
bCT with 2D and 2D+3D mammography.  The 4th bCT scanner (“Doheny”) is now 
operational and has four times the spatial resolution of our earliest scanner.  Non-
contrast bCT has demonstrated better mass-lesion detection performance than 
mammography (Lindfors, et al, 2008) but using the earlier bCT systems, 
microcalcification detection was inferior to mammography.  Doheny now has 
vastly improved spatial resolution, and we hypothesize that bCT is (now) equal to 
or better than screening mammography for microcalcification detection. In this 
aim, digital mammography and non-contrast bCT images will be compared in a 
standard receiver operating characteristic (ROC) study.  Mammography with 
Tomosynthesis will also be compared against non-contrast bCT, using ROC 
methods.  A full-search methodology will be used. 
 
Specific Aim 5:  High Risk Screening Performance: CE breast CT and CE-breast MRI.  
To evaluate the potential of CE-bCT for use in high risk screening (as MRI is used 
now), CE-bCT ROC performance will be compared against CE-MRI ROC 
performance.  Radiologists will perform full 3D search of the CT and MRI 
(independently) volume data sets (both with and without contrast) and report 

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overall probability of malignancy for each modality.  Location-specific metrics for 
potential FROC or LROC analysis will also be captured.  Assessment of ΔHU will also 
be performed to quantitatively evaluate predictive performance for malignancy. 
 
Specific Aims 1 and 2 do not require changes in hardware; these two aims are 
completely focused on post-acquisition image processing techniques (software). 
Therefore, accrual to the clinical trials as described in Aim 3 can commence on day 
one of this project. The acquired projection image data from the scanner is always 
saved, and once the scatter-correction and flat fielding techniques (Aim 1) and 
optimized reconstruction methods (Aim 2) are finalized, images will be re-
reconstructed and become available for the ROC studies on normal-risk screening 
(Aim 4) and high-risk screening (Aim 5) performance.  We believe that this 5 year 
study will demonstrate that non-contrast bCT can outperform 2D & 3D 
mammography in breast cancer screening for normal risk patients, and that CE-
bCT is (at least) equivalent to CE-MRI for screening high-risk women. 
 
3) 
Background 
 
Breast cancer is a disease with high incidence that will affect the life of one of 
every eight women in the United States. Early detection of breast cancer is the 
most important factor determining prognosis, and X-ray mammography is the 
principal screening tool for breast cancer world-wide. While mammography is not 
without shortcomings, it nevertheless plays an important and documented role in 
reducing mortality associated with breast cancer. The principal weakness of 
mammography is in its application to women with extremely dense, glandular 
breasts. Imaging the dense breast with good sensitivity has taken on more 
importance as younger women (40-49 year age group) are now screened routinely, 
as the use of hormone replacement therapy has expanded, and as genetic testing 
identifies younger women at risk. Equalization techniques have been shown to 
increase the effective dynamic range of mammography, however their technical 
complexity has hampered widespread adoption. Digital radiographic systems, 
finally nearing wide-scale clinical use, have the promise of improving 
mammography of the dense breast due to their increased dynamic range over 
screen-film mammography. However, like screen-film mammography, digital 
mammography integrates all anatomical structures in the breast onto a planar 
projection image. The fundamental problem of detecting breast cancer in dense 
breasts is the superposition of multiple overlaying glandular structures, which can 
obscure the visualization of a breast tumor. A fundamental solution to this 
problem lays in the use of tomographic imaging techniques, which vastly reduces 

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anatomical complexity by separating overlapping structures into individual 
tomographic images of the breast. 
 
Summary of Initial Experience 
 
Dedicated breast computed tomography (bCT) is a fully tomographic cone beam x-
ray based imaging modality that generates three dimensional images of the breast. 
In initial clinical trials, bCT was shown to provide significantly better visualization 
of mass lesions than that capable with mammography; however mammography 
outperformed bCT in visualizing microcalcifications.[1] Further work using injected 
iodine based contrast medium in conjunction with bCT, or so called contrast-
enhanced bCT (CE-bCT), verified that mass lesions are seen better on CE-bCT than 
on mammography. However, the visualization of microcalcifications, specifically 
those associated with a malignant lesion, was similar at CE-bCT and 
mammography, suggesting that the use of iodine contrast medium may close the 
gap between bCT and mammography in visualizing malignancy.[2] Due to the 
contrast injection, CE-bCT is a more invasive procedure than mammography and 
may not be appropriate as a modality for breast cancer screening in the general 
population. CE-bCT may have more potential as a tool for screening in high risk 
patients, for cancer staging, and for tumor targeting. Unenhanced bCT may still 
serve as an important imaging modality for tumor staging and targeting in patients 
with contraindications to iodine contrast imaging. 
 
Contrast Enhanced Breast CT Significance 
 
Contrast injections are used to identify breast cancer lesions in clinical procedures, 
most notably breast MRI (gadolinium contrast agent).  Other investigators have 
demonstrated the utility of iodine contrast agent injection for breast cancer 
delineation in projection mammography techniques, using both dual energy 
subtraction (Lewin) and temporal subtraction (Yaffe) to highlight the visualization 
of the breast tumor. 
 
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22. Chang CH, Sibala JL, Fritz SL, Dwyer SJ, III, Templeton AW. Specific value of 
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39. Tabar L. Natural History of Breast Cancer. RSNA Scientific Assembly and 
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Radiology: Volume 256: Number 3-September 2010; 714-723.  
 

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4) 
Inclusion and Exclusion Criteria 
 
Inclusion Criteria: 
 
• Age at least 35 years old 
• Diagnostic findings from prior mammography highly suggestive of breast 
malignancy (BI-RADS® category 4 or BI-RADS® category 5) 
• Not pregnant or breast-feeding 
• Ability to lay still and hold breath for approximately 15 seconds 
 
Exclusion Criteria: 
 
 
• Recent breast biopsy 
• History of moderate or severe reaction to contrast agent injection (these 
    subjects can still participate in the non-contrast CT scanning) 
• History of Allergy to Iodine     
• History of multiple food and/or drug allergy    
• Currently taking Glucophage or Glucovance (Metformin)    
• History of Chronic Asthma    
• History of Diabetes Mellitus   
• Renal (kidney) disease, or solitary kidney    
• Recent lab tests showing elevated serum creatinine (≥ 1.5 mg/dL)   
• Recent lab tests showing estimated glomerular filtration rate (eGFR) ≤ 60 
ml/minute 
• Positive urine pregnancy test or currently breast-feeding 
• Inability to understand the risks and benefits of the study 
● The standard MRI contraindications apply, including but not limited to: having a 
pacemaker or other implanted electronic device, metal foreign bodies within the 
eye, aneurysm clips, heart valve prosthesis, vascular stents, coils, intrauterine 
devices (IUDs), inferior vena cava (IVC) filters, gunshot wounds with retained 
bullet fragments. (MRI only) 
• Prisoners 
 
 
Subject candidates will be informed of the study’s existence when they are told 
that they need a biopsy. Posters will also advertise the clinical trial, and the 
posters will be placed in the scan rooms and consultation areas. Brochures will 
also be available in the mammography facility (Suite 0500 ACC).  Mammography 
staff including technologists, clinical coordinators, fellows, or radiologists will 
inform the patient of the clinical trial. If the patient expresses an interest, a 
mammography technologist or study coordinator will review their eligibility and 
obtain contact information for a subsequent phone call. Patients may also be given 
a brochure by the scheduler, at the time of scheduling their biopsy.  Patients who 
have expressed an interest or who have taken a brochure will be called by the 

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study coordinator, who will use a script. If the candidate agrees to participate, the 
coordinator will schedule the MRI scan and breast CT scans. 
 
5) 
Study Timelines 
 
The duration of the subject’s active participation is approximately 1.5 hours. 
The duration of the subject’s pathology follow-up is ~2-3 months. 
The estimated date to complete the study is approximately December 31, 2022. 
 
6) 
Study Endpoints 
 
Primary: The primary study endpoint will be the assessment of patient safety and 
comfort at the conclusion of the imaging phase of the study. 
 
Secondary: The secondary study endpoint will be the comparison of breast MRI 
versus breast CT in terms of sensitivity and specificity using biopsy findings as the 
standard of truth for lesion characterization. True positives & negatives and false 
positive & negatives will be defined and ROC (receiver operating characteristics) 
curves will be generated. 
 
7) 
Procedures Involved 
 
The patient’s biopsy appointment typically occurs about 1 week after her 
diagnostic work-up in the Mammography clinic. Breast CT and breast MRI scans 
may take place on different days, or both may be done on the day of her biopsy 
appointment. Whichever is done first will depend on the clinical MRI clinic 
schedule. The second scan, whether it is breast CT or breast MRI, will take place 
prior to the subject’s scheduled breast biopsy appointment. 
 
Breast CT: 
 
The subjects will arrive at the Ambulatory Care Center, Suite 0500 on the day of 
their study breast CT. The woman to be scanned will lie prone on a large table 
(which is covered by a foam pad), and she will place the breast to be scanned in a 
small hole in that tabletop. The hole is surrounded by a soft neoprene “hammock,” 
which will allow the woman’s entire upper torso to slump into the scan plane of 
the device. After positioning of the breast by a female mammography 
technologist, two single projection scout images will be acquired to confirm proper 
positioning and two additional single projection images will be acquired with a 
tungsten collimator placed at the X-ray tube for scatter correction. The woman will 
be instructed to hold her breath (for approximately 15 seconds) and the scan will 
commence. There will be no breast compression (as in mammography), and other 

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than the sound of the relatively noisy x-ray system in the room, the woman will 
not feel or sense any aspect of this scan. 
 
Contrast Injection Procedures 
 
(Note: If the study subject cannot tolerate iodinated contrast, or IV placement is 
not possible, the subject may still participate in the non-contrast CT scanning.) 
 
After aseptically prepping the patient’s skin, a intravenous catheter will be 
inserted into the antecubital vein. The patient will be positioned in the scanner as 
described above and the IV will be connected to the power injector. 100 ml of 
contrast agent (Omnipaque-350 350 mg I/ml) at a rate of 4ml/sec will be injected 
over the course of approximately 25 seconds. In the event the subject has bilateral 
breast lesions, the contrast administration will be split into two separate 
injections. 50 ml of contrast at 4ml/sec will be injected prior to scanning the first 
breast, and a second 50 ml at 4ml/sec will be injected prior to imaging the second 
breast. The total radiation dose will be the same as that for those subjects who 
receive the single 100 ml contrast injection. Post-contrast CT scanning will begin 
approximately 90 seconds after the start of injection. This time point represents 
the expected peak concentration of contrast in the circulation. Total time for this 
visit is approximately 45 minutes. 
 
Breast MRI: 
 
The subjects will arrive at the Ambulatory Care Center, Suite 0500 on the day of 
their study breast MRI. After screening by an MRI technologist for MRI 
contraindications, an I.V. will be placed in the subject’s forearm. The subject will 
then be positioned on the scan table prone, with each breast hanging into 
separate holes of the MRI coil. Pre-contrast scanning will then take place (short T-1 
inversion recovery (STIR) and T-1 weighted pulse sequences). MRI contrast will 
then be injected (Omniscan (Gadodiamide) GE Healthcare) at a dose of 0.2 ml/kg 
and at a rate of 2 ml/second by a power injector. 15-20 ml of normal saline will be 
used as a flush. Post-contrast scanning will then take place. Following this, the 
subject’s visit will be complete. Total time for this visit is approximately 45 
minutes. 
 
 
 
NOTE: If a subject wishes to participate, but cannot or will not, undergo MRI 
scanning, the subject may still be enrolled for the CT portion only. 
 
 
After the scans have finished, the participant will be given a questionnaire to 
complete about their experience during the study.  After completion of the scans 
and completing the questionnaire, their active participation in the study will be 

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completed.  Access to their medical record for follow up information may 
continue. 
 
8) 
Data and/or Specimen Management and Confidentiality 
 
Statistics and Determination of Study Sample and Data Analysis: 
 
For this next cohort of 400 subjects, the following statistical analysis has been 
performed: 
 
Over the past three years, the UC Davis breast imaging facility has averaged 15,818 
screens, 2,665 diagnostic exams, and 480 biopsies annually. Patient recruitment 
will be ongoing during the first 4 years of the proposal, so that a “forgetting” time 
of at least 6 months can be enforced from the time of imaging to the reader 
studies. All cases will be recruited from BIRADS 4 & 5 women who will be biopsied 
in our facility, and we assume the historical 38% positive biopsy rate for our 
facility. The recruited women will undergo pre- and post- contrast bCT imaging, as 
well as pre- and post- contrast CE-MRI imaging. These women will all have had 
bilateral 2D and 3D mammography imaging as part of their screening and 
diagnostic workup. The biopsy findings will serve as ground truth for all cases. In 
addition, the vast majority of women will have all findings limited to a single 
breast, leaving the unaffected breast available as a non-cancer image (i.e. normal) 
for the screening study in Aim 4. Based on the power studies described below, the 
minimum number of women we need to recruit to run the study is 150 with 
biopsy-verified cancer and an additional 50 with benign findings (i.e., 150 / 0.38 = 
395 ≈ 400). At a minimum, we plan to recruit 400 and will strive to recruit 
substantially more. Given a total of 1,920 candidate women, the 38% positive rate 
for biopsy, and a 25% rate of recruitment, we would expect to be able to acquire 
182 cases (1920 × 0.38 × 0.25) with cancer over the recruitment period, and this 
would corresponding to ~298 (1920 × 0.25 × [1-0.38]) women with benign findings. 

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These recruitment figures are conservative in terms of the recruitment rate, and 
they still provide more than enough cases for our studies. 
 
Numbers of patients needed: To size the studies, we have conducted power 
analyses [Abbey et al., 2013] based on the Roe and Metz simulation (2,000 runs) 
for a fixed effects ANOVA model instead of the usual mixed effects model 
proposed by Dorfman, Berbaum, and Metz (DBM) or correlated error model of 
Obuchowski and Rockette (Hillis SL, et al., 2005). For the normal-risk bCT-screening 
study (Aim 4), we have sized the study on the basis of 4 readers, an improvement 
of 0.05 in AUC, and with average AUC near 0.85 (i.e. AUC = 0.825 vs AUC = 
0.875). At these performance benchmarks, 82% power is achieved with 150 
positive cases and 250 negative cases. This is a reasonable number of cases given 
the recruitment procedures described in §D3.1. For the CE-bCT/CE-MRI (high risk  
screening) comparison (Aim 5), we investigate the non-inferiority of breast CT 
relative to MRI. We will consider breast CT to be successful in the pilot study if the 
observed difference in reader-averaged AUC values is greater than -0.025 (i.e. 
AUC(BCT) – AUC(MRI) > -0.025), for a study in which average AUC is approximately 
0.85. The Roe and Metz simulation [Abbey, et al, 2013] with 4 readers and 150 
cases (60 positive and 90 negative) yields 82% power for finding non-inferiority as 
defined above in 2,000 independent simulation runs. We expect to be able to 
recruit at least this many patients for this study based on the recruitment 
procedures described above. 
 
 
Informed consent and subject accountability: 
 
 
There will be a clear accounting of all subjects involved with the study. This 
includes subjects who are consented, screened, eligible and enrolled as well as 
ineligible subjects. If a candidate is deemed ineligible for enrollment, the reason 
for ineligibility will be recorded. There will also be a listing of all patients 
discontinued or withdrawn from the study after enrollment. These statistics will be 
reported to the IRB during annual reviews when required. 
 
All subjects participating in this study will provide written consent in the form of 
the Informed Consent Form. The investigators will allow the candidate to read the 
consent form and will ask the candidate if they have any questions prior to 
enrollment. Subject initials, signatures, and date and time will be required in the 
appropriate places on the form. 
 
 
 
Data Handling and Data Management: 
 
The data from all subjects will be used in the safety and efficacy evaluation. 
Documentation containing the subjects’ Protected Health Information (medical 
history, mammograms, ultrasound images, Breast CT images, breast MRI images, 

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biopsy reports) that is collected for research purposes will remain in the custody of 
study personnel (kept in a secure location), and will not be copied or discarded. 
This documentation will be de-identified after the data has been analyzed and the 
results are ready for publication. 
 
Source documentation will be identified by ink stamp which will include the initials 
of the study personnel recording the data and the date on which it was recorded. 
 
Written corrections to source documents will be made in the following manner: 
the corrected information will be written next to the information being corrected, 
and the information being corrected will be crossed out with a single line and the 
investigator’s initials and the date of the correction will be written next to the 
lined out information. 
 
Records Retention: 
 
All source documentation pertaining to the conduct of this study will be retained 
by the investigator for a period of 5 years following the closure of the study. This 
documentation includes screening mammography images, mammography exam 
reports, breast CT images, digital image data files, case report forms, biopsy 
reports, IRB correspondence and approvals, informed consent forms, urine 
pregnancy test reports, protocol deviations, and adverse event reports. 
 
 
Documentation containing the subjects’ Protected Health Information (name, 
medical record number, medical history) that is used for recruitment purposes will 
remain in the custody of study personnel, and will not be copied or discarded. No 
identifiers, used for recruitment purposes, will be disclosed to a third party except 
as required by law or for authorized oversight of the research project. 
 
9) 
Data and/or Specimen Banking 
 
Breast CT images maintained on the laboratory redundant array of independent 
disks (RAID) will be banked for future image processing development work 
covered under a separate IRB protocol. The images will not contain any 
identifiers when they are used for this purpose. 
 
10) Provisions to Monitor the Data to Ensure the Safety of Subjects 
 
Physical presence of a licensed technologists, and a physician during the scanning 
procedure. 
 
The IRB form HRP-214 Reportable New Information will be used to report all 
serious, unanticipated, and related adverse events to the UC Davis IRB 
Administration within 5 days of occurrence. This form will also be used to 

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document minor, anticipated, and/or unrelated adverse events for annual IRB 
review. 
 
11) Withdrawal of Subjects 
 
A subject will be considered to have successfully completed their participation in 
the study at the conclusion of the scanning procedure. If a subject is removed or 
withdraws from the study, the specific reasons for discontinuation will be clearly 
documented in the subject’s study file. 
 
12) Risks to Subjects 
 
This study involves a small amount of radiation exposure that is typical of other 
diagnostic tests involving the use of radiation exposure (such as a mammogram). 

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The amount of radiation exposure received in this study is below the levels that 
are thought to result in a significant risk of harmful effects. 
 
Risks associated with iodine-based IV contrast injection are as follows: 
 
Minor/Common risks:                                       Severe/Rare risks: 
● Bruising/infection at the IV site                  ● Pulmonary edema 
● Nausea & vomiting                                        ● Respiratory arrest 
● Urticaria                                                          ● Cardiac arrest 
● Pruritis                                                             ● Seizures  
● Diaphoresis 
 
Moderate/Uncommon risks: 
● Faintness  
● Facial edema  
● Laryngeal edema  
● Bronchospasm  
 
Risks associated with gadolinium-based IV contrast injection are as follows: 
 
Minor/Common risks: 
● Bruising/infection at the IV site 
 
Severe/Rare risks: 
● Nephrogenic Systemic Fibrosis (NSF) 
 
Risks associated with MRI scans are as follows: 
 
Minor/Common risks: 
● Claustrophobia 
 
Special IV Contrast Patient Safety Precautions: 
 
A doctor will be present during each contrast-enhanced breast CT and MRI scan to 
monitor the subject for signs and symptoms of adverse reaction to the contrast 
injection. A fully-stocked hospital-issued crash kit will be available for emergency 
treatment. Emergency Medical Services (EMS) will be called for immediate 
transport to the UCDMC emergency department.  Verbal and written post contrast 
instructions will be provided to the patient at the end of the study visit. 
 
13) Potential Benefits to Subjects 
 
Breast CT images will not be used for diagnosis or treatment planning, and will 
provide no direct benefit for subjects. Breast MRI scans are the imaging Gold 

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Standard for breast lesion clinical diagnosis, and the MRI scans performed for this 
study will be interpreted by a radiologist with the reports available in the subject’s 
medical record. These findings will be available to the subject’s referring or 
primary care physician. 
 
14) Multi-Site Research 
 
Not applicable. 
 
15) Community-Based Participatory Research 
 
Not applicable. 
 
16) Sharing of Results with Subjects 
 
Breast CT images and data will not be shared with subjects. 
 
17) Prior Approvals 
 
This protocol has been approved by the Cancer Center Scientific Review 
Committee (UCDCC#162) and the Radiation Use Committee. 
 
18) Provisions to Protect the Privacy Interests of Subjects 
 
Documentation containing the subjects’ Protected Health Information (medical 
history, mammograms, Breast CT images, biopsy reports) that is collected for 
research purposes will remain in the custody of study personnel in a secure 
location and will not be copied or discarded. This documentation will be de-
identified after the data has been analyzed and the results are ready for 
publication. 
 
19) Compensation for Research-Related Injury 
 
The following standard language is stated in the Informed Consent  Form: It is 
important that you promptly tell the Researcher if you believe that you have been 
injured because of taking part in this study.  If you are injured as a result of being 
in this study, the University of California will provide necessary medical treatment.  
The costs of the treatment may be covered by University or the study sponsor or 
may be billed to your insurance company just like other medical costs.  The 

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University and the study sponsor do not normally provide any other form of 
compensation for injury. You do not lose any legal rights by signing this form. 
 
20) Economic Burden to Subjects 
 
None. 
 
21) Drugs or Devices 
 
Breast Computed Tomography (CT) scanner. The device was fabricated in the 
Principal Investigator’s laboratory.  The major hardware components (x-ray 
generator, x-ray tube, x-ray detector, computer-controlled motor) were purchased 
from vendors. The MRI scanner is a General Electric 1.5 Tesla magnet used for 
clinical service. 
 
☐ I confirm that all investigational drugs will be received by the Investigational 
Drug Service (IDS).  The IDS will store, handle, and administer those drugs so 
that they will be used only on subjects and be used only by authorized 
investigators. 
 
☒ I confirm that all investigational devices will be labelled in accordance with 
FDA regulations and stored and dispensed in such a manner that they will be 
used only on subjects and be used only by authorized investigators. 
 
22) ClinicalTrials.gov Registration 
 
NCT00584233 
 
Section 1:  NIH Funded Studies 
If yes to BOTH, the study must be registered on Clinicaltrials.gov. 
Yes  
 
This study is funded by the NIH. (If this study is not funded by NIH, go to Section 
2.) 
 
One or more human subjects will be prospectively assigned to one or more 
interventions (which may include placebo or other control) to evaluate the 
effects of those interventions on health-related biomedical or behavioral 
outcomes. 
 
 
 

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23) Criteria for 10 Year Approval  
 
If yes to all items below this research may qualify for a 10-year approval period. 
 
Yes  
 
This research involves no more than minimal risk. 
 
This research does not receive any federal or state government funding or 
funding from a private funder who requires annual review per contract. 
 
This research is not subject to FDA jurisdiction.  
 
This research does not include prisoners as participants. 
 
This research is not subject to SCRO oversight. 
 
This research is not subject to oversight by the Research Advisory Panel of 
California (RAP of C). 
 
This research does not involve identifiable information held by the State of 
California Department or Agency 
 
No personnel involved in the design, conduct, or reporting of this research have 
a new unreported related financial interest (RFI) in this study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                             
 
 

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Appendix 1 
 
 
 
 
                                               “Evaluation of Breast CT” 
 
                                   URINE PREGNANCY TEST REPORT 
 
 
 
                                                     ______________________      
                                                          Candidate’s Name/MRN                                          
 
 
Test Result:                     □ Positive                                 □ Negative 
 
 
 
 
________________________________    ___________________  __________________ 
    Signature of Study Candidate                               Date                             Time 
 
 
 
________________________________    ___________________  __________________ 
     Signature of Investigator                                     Date                             Time 
 
 
Name:__________________________ 
MRN:___________________________ 
 
 
 
 

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Appendix 2 
 
Inclusion/Exclusion Checklist 
 
 
Inclusion Criteria: 
 
 Age at least 35 years old 
 Diagnostic findings from prior mammography highly suggestive of breast 
malignancy (BI-RADS® category 4 or BI-RADS® category 5) 
 Not pregnant or breast-feeding 
 Ability to lay still and hold breath for approximately 15 seconds 
 
 Exclusion Criteria: 
 
 
 Recent breast biopsy 
 History of moderate or severe reaction to contrast agent injection (these 
    subjects can still participate in the non-contrast CT scanning) 
 History of Allergy to Iodine     
 History of multiple food and/or drug allergy    
 Currently taking Glucophage or Glucovance (Metformin)    
 History of Chronic Asthma    
 History of Diabetes Mellitus   
 Renal (kidney) disease, or solitary kidney    
 Recent lab tests showing elevated serum creatinine (≥ 1.5 mg/dL)   
 Recent lab tests showing estimated glomerular filtration rate (eGFR) ≤ 60 
ml/minute 
 Positive urine pregnancy test or currently breast-feeding 
 Inability to understand the risks and benefits of the study 
 The standard MRI contraindications apply, including but not limited to: having 
a pacemaker or other implanted electronic device, metal foreign bodies within 
the eye, aneurysm clips, heart valve prosthesis, vascular stents, coils, 
intrauterine devices (IUDs), inferior vena cava (IVC) filters, gunshot wounds 
with retained bullet fragments. (MRI only) 
 Prisoners 
 
 
________________________________    ___________________  __________________ 
     Signature of Investigator/Study Personnel                           Date                             Time