The Value of Advanced MR Imaging in Gynecological Tumors and Benign Uterine Fibroids
Phase: NA
Conditions: Gynecologic Tumor
Sponsor: Dana-Farber Cancer Institute

The Value of Advanced MR Imaging in Gynecological Tumors and Benign Uterine Fibroids 
 
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DF/HCC NON-CLINICAL PROTOCOL TEMPLATE 
Version Date: October 2, 2017 
 
 
 
PROTOCOL TITLE: 
The Value of Advanced MR Imaging 
in Gynecological Tumors and Benign Uterine Fibroids 
 
PRINCIPAL INVESTIGATOR: 
Dr. Clare Tempany MB BAO BCh, FACR, FISMRM 
Department of Radiology 
Tel: 617-732-7858 
ctempany@bwh.harvard.edu 
 
VERSION NUMBER: 
Version 1.0 
 
DATE: 
March 7, 2019 

The Value of Advanced MR Imaging in Gynecological Tumors and Benign Uterine Fibroids 
 
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Table of Contents 
1.0 
Objectives* ............................................................................................................. 3 
2.0 
Background* ........................................................................................................... 3 
3.0 
Inclusion and Exclusion Criteria* ........................................................................... 5 
4.0 
Study-Wide Number of Subjects* .......................................................................... 6 
5.0 
Study-Wide Recruitment Methods* ....................................................................... 6 
6.0 
Multi-Site Research* .............................................................................................. 6 
7.0 
Study Timelines* .................................................................................................... 6 
8.0 
Study Endpoints* .................................................................................................... 6 
9.0 
Procedures Involved*.............................................................................................. 6 
10.0 
Data and Specimen Banking* ................................................................................. 8 
11.0 
Data Management* and Confidentiality ................................................................. 8 
12.0 
Provisions to Monitor the Data to Ensure the Safety of Subjects* ......................... 9 
13.0 
Withdrawal of Subjects* ....................................................................................... 10 
14.0 
Risks to Subjects* ................................................................................................. 10 
15.0 
Potential Benefits to Subjects* ............................................................................. 10 
16.0 
Vulnerable Populations* ....................................................................................... 10 
17.0 
Community-Based Participatory Research* ......................................................... 10 
18.0 
Sharing of Results with Subjects* ........................................................................ 11 
19.0 
Setting ................................................................................................................... 11 
20.0 
Resources Available.............................................................................................. 11 
21.0 
Prior Approvals ..................................................................................................... 11 
22.0 
Recruitment Methods ............................................................................................ 11 
23.0 
Local Number of Subjects .................................................................................... 11 
24.0 
Provisions to Protect the Privacy Interests of Subjects ......................................... 12 
25.0 
Compensation for Research-Related Injury .......................................................... 12 
26.0 
Economic Burden to Subjects ............................................................................... 12 
27.0 
Consent Process .................................................................................................... 12 
28.0 
Process to Document Consent in Writing ............................................................. 13 
29.0 
Drugs or Devices................................................................................................... 13 
30.0 
References ............................................................................................................. 13 
 

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1.0 
Objectives* 
Magnetic Resonance Fingerprinting (MRF) and Q-space Trajectory Imaging (QTI) are 
advanced new magnetic resonance imaging (MRI) sequences that provide rapid 
quantitative tumor metrics and enable visualization of the tumor microstructure, 
respectively. This would have substantial value in diagnostics and tumor characterization 
in cases such as insufficient biopsy specimens, MRI-guided treatment planning, and in 
evaluating treatment response and differentiating residual tumor from treatment related 
changes. Furthermore, quantitative metrics from MRF and QTI may provide prognostic or 
predictive biomarkers that guide the proper oncologic workup and treatment for the 
patient. We hypothesize that QTI provides deeper insight into the tissue microstructural 
environment and that quantitative metrics from QTI and MRF accurately characterize the 
gynecological malignancy in comparison with the tumor histology. Furthermore, we 
hypothesize that MRF and QTI provide prognostic information valuable to the patient and 
treating physician. 
 
Primary Objective 
• to investigate the feasibility of advanced MRI sequences in participants with 
gynecologic malignancy and in control participants with benign uterine fibroids 
by measures of image quality and by comparing the MRI parameters between 
different tumor entities and normal anatomic structures  
 
Secondary Objectives 
• to study the diagnostic value of MRF and QTI in characterizing the tumor by 
comparing the tumor parameters with normal structures, benign fibroids, and 
tumor histology 
• to study the prognostic value of MRF and QTI by comparing tumor parameters 
with treatment effect and participant outcome 
 
2.0 
Background* 

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Uterine cervical, endometrial, and ovarian cancer are the most common gynecologic 
malignancies, with cervical cancer being worldwide the leading cause of cancer-related 
death in women. Conventional MRI is routinely used in gynecologic malignancies for its 
ability to depict the extent of disease at diagnosis providing guidance in staging and 
treatment planning [1–3]. Diffusion weighted imaging (DWI) and dynamic contrast 
enhanced MRI further improve tumor delineation and characterization and are often 
included into standard protocol [4]. Moreover, DWI has shown promise regarding 
histological grading and subtype differentiation within endometrial and cervical cancer, 
however, results are not fully consistent [2, 5]. 
 
MRF is a recently introduced approach in accelerating multiparametric quantitative MR 
imaging [6]. Quantitative MRI methods, as opposed to traditional visual assessment of 
images, provide objective parameters and would particularly be advantageous in oncology 
for diagnosis, treatment response assessment and follow-up to reduce subjectivity of image 
interpretation. Traditional quantitative MRI approaches, however, are relatively slow and 
provide only a single property at a time. In MRF, multiple tissue properties are acquired 
simultaneously by randomly varying the sequence parameters [7]. Pattern recognition is 
then used to compare each voxel’s signal fingerprint with a dictionary of anticipated 
combinations of tissue properties, to identify the best match of a tissue property for that 
voxel. MRF enables simultaneous measurement of multiple tissue properties such as T1, 
T2, T2*, B0, proton density, and perfusion. MRF has mainly been employed in brain 
imaging [8]. Recently, the proof-of-principle for using MRF in abdominal imaging and 
prostate cancer, was reported [9, 10]. 
 
QTI is a framework for advanced diffusion MRI that enables imaging of the tissue 
microstructure on a sub-voxel level that is not possible with the traditional diffusion MRI 
[11, 12]. By using q-space trajectory encoding and a diffusion tensor distribution model, 
QTI improves the discrimination of diffusivity, shape, and orientation of diffusion 
microenvironments and therefore carries major potential for imaging the tumor 
microenvironment. The feasibility of QTI in brain MR imaging has been shown in pilot 
studies involving patients with schizophrenia and brain tumor [12–14]. Furthermore, 

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studies that investigate the role of QTI in unraveling the microstructure of both brain and 
prostate cancers are in progress at Brigham and Women’s Hospital (BWH). Neither MRF 
nor QTI have previously been studied in gynecological malignancies. 
 
3.0 
Inclusion and Exclusion Criteria* 
Patients with gynecological cancer who are referred to receive treatment at Brigham and 
Women’s Hospital (BWH) and/or Dana-Farber Cancer Institute (DFCI), and who will 
undergo routine clinical standard of care pelvic MRI, are eligible to participate in the study. 
Subjects with benign uterine fibroids referred to routine pelvic MRI at BWH will serve as 
controls. 
 
Inclusion Criteria 
• Participants with suspected or histologically confirmed diagnosis of primary or 
recurrent gynecological cancer including uterine endometrial, cervical, vaginal, 
vulvar, ovarian, and smooth-muscle tumors undergoing routine clinical standard of 
care pelvic MRI 
• Control subjects with benign fibroids undergoing routine clinical standard of care 
pelvic MRI 
• Age ≥ 18 years 
• ECOG performance status of ≤ 2, based on treating physician’s discretion 
(Appendix A) 
• Ability to understand and the willingness to sign a written informed consent 
document 
 
Exclusion Criteria 
• Contraindication to MRI identified by the MR procedure screening form, such as a 
pacemaker, aneurysm clip, inner ear implant, neurostimulator, or other MR non-
compatible device or implant 
• Uncontrolled intercurrent illness including, but not limited to ongoing or active 
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac 

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arrhythmia, or psychiatric illness/social situations that would limit compliance with 
study requirements 
• Adults unable to consent 
• Non-english speaking subjects 
• Pregnant women 
• Prisoners 
 
4.0 
Study-Wide Number of Subjects* 
N/A 
 
5.0 
Study-Wide Recruitment Methods* 
N/A 
 
6.0 
Multi-Site Research* 
N/A 
 
7.0 
Study Timelines* 
Participation in this research study requires 10–15 minutes additional scanning time to 
perform QTI or MRF along with the routine clinical standard of care pelvic MRI. No other 
procedures or extra hospital visits are required by the participants. Anticipated duration to 
enroll all study subjects is 1–2 years. The estimated date to complete this study (complete 
primary analyses) is 05/31/2021. 
 
8.0 
Study Endpoints* 
Please see section 1.0 for primary and secondary study objectives. 
 
9.0 
Procedures Involved* 
The eligibility of participants with gynecologic cancer will be evaluated by the treating 
gynecologic surgeon or oncologist during the routine standard of care practice at 

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BWH/DFCI. If a participant meets the inclusion criteria, she will be informed about the 
study both orally and in paper by handing out the informed consent form. If the subject is 
willing to participate in the study, her signature to the consent form is obtained by the 
treating physician at the end of the appointment. In case the participant requests time for 
reflection, the consent signature can be obtained just prior to MRI by the research 
coordinator. 
 
The eligibility of control participants with benign fibroid(s) is evaluated by the treating 
interventional radiologist based on the referral and a phone call made to the participant to 
give information about the study (Phone Script in Appendix B). Upon eligibility, informed 
consent will be sent by email or mail. Signature to the consent form will be obtained by a 
research coordinator prior to the MRI scan. 
 
If the subject is willing to participate in the study, the advanced MRI sequence (either QTI 
or MRF) will be run along with the routine standard of care MRI. If the subject wishes not 
to participate, only standard of care MRI sequences will be performed according to the 
routine protocol. 
 
Institutions will register eligible participants in the Clinical Trials Management System 
(CTMS) OnCore as required by DF/HCC SOP REGIST-101. When required by REGIST-
101, registration must occur prior to the initiation of protocol-specific procedures or 
assessments. 
 
Routine clinical standard of care pelvic MRI will be performed using a clinical 3T MRI 
scanner at BWH. The advanced MRI sequence (MRF or QTI) will be supplementary and 
included along with the current clinical exam. No invasive procedures are needed for MRF 
or QTI. No extra hospital visit is required related to this study. The duration of routine 
clinical pelvic MR exam is approximately 30–45 minutes. Running MRF or QTI along 
with the routine clinical protocol will add this scanning time by approximately 10–15 
minutes. There are no reported toxicities related to MRI itself when all the safety guidelines 
are being followed. No intravenous contrast agent is needed for the advanced MR 

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sequences (QTI and MRF). Scanning time will be increased with 10–15 minutes which 
may cause discomfort to participants due to laying on the scanning table for a longer period 
of time. 
 
Follow-up data including treatment outcome, tumor histology, clinical variables, 
laboratory results, medical images, and survival data, will be collected from the 
participant’s electronic medical records. For survival data, the duration of follow-up is up 
to 4 years after participation and the MRI scan with new MRI methods. 
 
10.0 Data and Specimen Banking* 
N/A 
 
11.0 Data Management* and Confidentiality 
11.1 Data analysis plan and statistical procedures 
Primary endpoint of this study is to evaluate the feasibility of MRF and QTI in 
gynecological pelvic MRI. Feasibility will be assessed in two ways. First, the 
aspects of image quality such as artifacts, sharpness, and noise will be evaluated by 
two radiologists. Second, regions-of-interest (ROI) of the tumor and normal tissue 
(uterine normal endometrium, myometrium, cervical stroma, ovaries) will be 
recorded and ROI-based parameters from MRF (T1 and T2 relaxation values) and 
QTI (total mean kurtosis MKT, microscopic anisotropy MKA, isotropic 
heterogeneity MK1, fractional anisotropy FA, microscopic fractional anisotropy 
µFA) will be compared between the tumor and normal tissue, and between different 
tumor histologies. One-way analysis of variance will be used to determine the 
statistical difference of each MRF and QTI value between the malignant tumors, 
benign fibroids, and normal tissue.  
 
Secondary endpoint is to assess the predictive and prognostic value of MRF and 
QTI in gynecological malignancies. For this purpose, MRF and QTI parameters 
from gynecological malignancies will be compared with the treatment effect 

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assessed by clinical examination and/or cross-sectional follow-up imaging, and the 
participants’ outcome by means of Kaplan-Meier method with log rank test, and 
Cox proportional-hazards model. 
 
Variables that will be collected include the quantitative MRI parameters, 
demographic information (age, sex), clinical variables (diagnosis, tumor stage, 
histopathologic and molecular data, laboratory results, treatment, dates of diagnosis 
and treatments), follow-up images, and outcome data (recurrences, survival). An 
Excel database including MRI and clinical variables will be developed for the 
purposes of this study. 
 
11.2 Power analysis 
The sample size calculation is exploratory in nature since no protocols with 
MRF or QTI in gynecological imaging have been published. One prior 
publication reports the range of traditional T2 relaxation values in one 
patient with endometrial cancer [15]. Based on the average value of 78 ms 
T2 relaxation time in endometrial cancer, and on the assumption of 5% 
difference to other histologies and SD of 5 ms, the calculated targeted 
sample size is 27 patients per group with power set at 80% and type I error 
rate of 5% (www.sample-size.net/sample-size-means/). 
 
11.3 Data safety and quality  
To secure the data during storage, use, and transmission, only investigators 
with the required training and authorization of access will analyze the data. 
All the computers handling the data will be encrypted and password-
protected. The principal investigator and the research group will be 
responsible for continuous monitoring of the data quality and data safety. 
 
12.0 Provisions to Monitor the Data to Ensure the Safety of Subjects* 

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N/A. This research proposal does not involve more than Minimal Risk to subjects. 
 
13.0 Withdrawal of Subjects* 
Participants will be removed from the study in case of a withdrawal of consent for data 
submission 
 
14.0 Risks to Subjects* 
There are no reported toxicities related to MRI itself when all the safety guidelines are 
being followed. No intravenous contrast agent is needed for MRF or QTI. Storing and use 
of data pose a minimal risk to the confidentiality and participant’s privacy. 
 
Potential risks, discomforts, and hazards related to MRI 
• Anxiety, stress 
• Claustrophobia 
• Discomfort due to laying on the scanning table for a longer period of time (10–15 
minutes) 
• Rare but serious: Injury associated with foreign bodies and the MR magnet; this is 
most likely to occur should the institution fail to ask or should a participant fail to 
inform the site of contraindications to MR use (e.g. presence of metallic or surgical 
implant or metal pieces in the body) 
 
15.0 Potential Benefits to Subjects* 
There are no expected direct benefits to participants included in this pilot study. 
 
16.0 Vulnerable Populations* 
N/A 
 
17.0 Community-Based Participatory Research* 
N/A 
 

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18.0 Sharing of Results with Subjects* 
Results will not be shared with participants. 
 
19.0 Setting 
Potential study subjects will be identified by the treating physician at BWH/DFCI. The 
following standard of care pelvic MRI will be scheduled into either one of the two clinical 
MRI scanners at BWH/DFCI that include the new sequence, QTI (3.0 Tesla Siemens 
Magnetom Prisma at Hale Building for Transformative Medicine) or MRF (3.0 Tesla 
Siemens Verio at BWH main building L1) upon the subject’s interest in participating into 
the study. 
 
20.0 Resources Available 
The primary research team involves the principal investigator and co-investigators. 
Investigators include radiologists and computer scientists who are experts in the field of 
diagnostic MRI, technical aspects of new advanced MRI sequences, and MRI analysis. The 
investigators also include treating physicians in the field of gynecological surgery, 
radiation oncology, interventional and diagnostic radiology, who will ensure that 
participants eligible for this study are recruited in line with the study objectives. All study 
staff will have completed required training per DF/HCC SOP EDU-100: Training 
Requirements for Research Personnel, prior to starting on any research procedures 
associated with this protocol. 
 
21.0 Prior Approvals 
N/A 
 
22.0 Recruitment Methods 
Please see section 9.0 for recruitment methods. 
 
23.0 Local Number of Subjects 

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Based on sample size calculation (see Section 11.2 Power Analysis), following number of 
participants will be included in this research study: 
1. MRF for participants with gynecologic malignancy; n=27 
2. MRF for participants with benign uterine fibroid; n=27 
3. QTI for participants with gynecologic malignancy; n=27 
4. QTI for participants with benign uterine fibroid; n=27 
 
24.0 Provisions to Protect the Privacy Interests of Subjects 
Personal health information (PHI) will only be used for research purposes and released 
solely to study staff listed on the protocol. The participant name and medical record number 
will be used to download images from PACS and to collect clinical information regarding 
treatment, pathology, and outcome from the medical record. All of these are obtainable 
only by using PHI which will be stored electronically on a password-protected encrypted 
computer. Participant’s clinical information will be coded using a unique code number 
identifier. Access to the code key linking the hospital identification number will be limited 
to the study investigators. Any clinical data shared with collaborators (statistician) will be 
supplied with code number identifiers only, without PHI. 
 
25.0 Compensation for Research-Related Injury 
No compensation is available since this research does not involve more than Minimal 
Risk to subjects. 
 
26.0 Economic Burden to Subjects 
Participating in the study will not lead to additional costs to the subjects. The routine 
clinical standard of care pelvic MRI is covered by the participant or her insurance company 
as usual. Subjects will not be charged for including QTI or MRF to the routine protocol. 
 
27.0 Consent Process 
Informed Consent Process according to SOP# CON-100 will be followed. Please see 
section 9.0 for the detailed consent process. 

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28.0 Process to Document Consent in Writing 
Informed Consent Process according to SOP# CON-100 will be followed. 
 
29.0 Drugs or Devices 
N/A 
 
30.0 References 
 
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