Assessment of Novel MRI Quantification Free Breathing Technique in Evaluation of Liver Lesions
Phase: NA
Conditions: Hepatocellular Carcinoma
Sponsor: Case Comprehensive Cancer Center

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2   
09-13-09c  CASE 3213  August1, 2017  V2.3  
Raj Mohan Paspulati, MD  
Department of Radiology  
  
  
University Hospitals Cleveland Medical Center  
  
  
  
  
 Case Western Reserve University  
 
  
 
  
 
STATISTICIAN:  
 
 
  
 
  
  
 
SPONSOR:  Case Comprehensive Cancer Center 
  
 
CLINICAL FACILITY: University Hospitals Cleveland Medical Center  
 
 
 
 
 
 

  
  
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09-13-09c  CASE 3213  August1, 2017  V2.3  
TABLE OF CONTENTS  
  
  
  
         
 
1.0  
Background and Rationale  
  
  
  
  
  
  
  
  
 
  
2.0  
Objectives   
  
  
  
  
  
  
  
  
  
  
3.0   
Selection of Patients/Samples  
  
  
  
  
  
  
  
 
4.0  
Registration Procedures   
  
  
  
  
  
 
5.0  
Research Plan  
  
  
  
  
  
  
  
  
  
6.0   
Study Parameters  
 
7.0  
Correlative Studies (if applicable)  
  
  
  
  
  
  
  
 
8.0  
Statistical Considerations   
  
  
  
  
  
 
    
  
  
9.0  
References  
  
  
  
  
  
  
  
  
 
 

 
  
  
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09-13-09c  CASE 3213  August1, 2017  V2.3  
Amendment History 
 
Protocol Version 2.3 Summary of Changes 01Aug/2017 
Section 1.0 
Background and 
Rationale 
No differentiation between patients receiving biopsies vs. those with benign 
lesions because we will not always be able to determine this prior to the liver 
intervention procedure.  Patients are rather categorized based on recruitment 
procedure i.e. those that are scheduled for an intervention vs. those undergoing 
MRI. 
Indication that the research DCE liver MRI will take less than 10 minutes. 
Section 3.0 Patient 
Sample/Selection 
No differentiation between patients receiving biopsies vs. those with benign 
lesions because we will not always be able to determine this prior to the liver 
intervention procedure.  Patients are rather categorized based on recruitment 
procedure i.e. those that are scheduled for an intervention vs. those undergoing 
MRI. 
Section 5.0 
Research Plan 
During personnel training, certain sections of the protocol were found to be 
repetitive or confusing.  These edits are administrative and do not change the 
study.  The language has been streamlined to remove repetition and for better 
readability. Inclusion criteria and recruitment procedures were updated to remove 
differentiation between biopsy patients and benign patients.   
Section 9.0  
Data Safety 
Monitoring Plan 
Addition of the following statement: Very small amounts of MRI contrast agents 
deposit in certain tissues of the body including regions of the brain, in patients 
who have received multiple doses of these agents. No known harm has been 
associated with the deposition, before or since the description of this deposition in 
2014. More than 300 million doses of gadolinium contrast have been given in 
humans since their first use. 
Section 10.0 
References 
References updated to include publication in support of the gadolinium deposition 
statement (section 9.0) 
 
 

 
  
  
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09-13-09c  CASE 3213  August1, 2017  V2.3  
1.0  
BACKGROUND AND RATIONALE   
SUMMARY: The primary objective of this study is to develop and validate simultaneous 
free-breathing 4D fat and water quantification and quantitative dynamic contrast enhanced 
perfusion in the liver. Secondary aims include developing and validating free breathing 
quantification of relaxation parameters T1 and T2, and developing and validating a minimal 
breath-hold (< 8 s) high quality diffusion exam using highly accelerated steady state 
diffusion imaging sequences. Investigators aim to scan 170 subjects who are scheduled for 
liver intervention or MRI exam of the liver. The study is greater than minimal risk. 
  
MR abdominal imaging made up 7% of the 30.2 million MRI examinations performed in the US 
in 2010, and liver MR is the most common abdominal exam [1]. MRI is extremely important in 
liver evaluation, where the capabilities to produce multiple and exquisite soft-tissue contrast and 
readily available multiphasic imaging without radiation risks have been leveraged to make it the 
technique of choice for lesion characterization. However, liver MR exams are complex, riddled 
with failures due to motion artifacts, and poor or variable lesion characterization due to small 
size, motion, and radiologist uncertainty in interpretation.   
 
 Almost every acquisition during an MR liver exam requires a breath-hold to limit motion 
artifacts. However, it is known that sicker patients provide shorter breath-holds [8]. Thus even 
with current fast imaging sequences, long breath-holds are difficult for patients, and result in 
non-diagnostic examinations. The direct cost of these exams, the missed diagnoses, the lost 
patient and physician time, the delays in treatment and inability to treat diseases properly means 
that the real dollar cost of motion in body MRI is immeasurable.   
 
 The second major set of problems with liver MRI is that of obtaining uniformly high quality 
exams and lesion characterization. Abdominal MRI is notoriously dependent on the quality of 
technologists because when motion or image quality issues arise, there are a myriad of adjustable 
parameters that require years of experience to master. The resulting images can be complicated 
by technical factors such as motion during the exam or simply small lesion size, differences in 
acquisition parameters and timings between exams, and difficulties in aligning the lesions on 
different kinds of contrast mechanisms. In the hands of experts, MRI liver characterization is 
often exquisite and definite, but in the hands of a majority of practicing radiologists, it is far from 
ideal.   
 These problems lead to frustration for both referring and interpreting physicians, and more 
importantly to biopsy of lesions for definitive diagnosis. If liver imaging could be converted to 
an ultra-fast examination performed at high spatial and temporal resolution, and at the same time 
provide quantitative information so that image characterization could be objective, the effect on 
clinical care could be significant. This would eliminate technically compromised exams, improve 
certainty in diagnosis, diminish the need for repeat or follow-up imaging, and most tantalizingly, 
potentially decrease the need for invasive tissue diagnosis. 
   
 We have developed techniques that we hope can turn the present standard liver examination into 
a high resolution exam that requires almost no breath-holds, and yet provides quantitative 
measures of all contrast mechanisms presently employed in the clinical standard examination. 
The research DCE liver MRI scan time will be less than 10 minutes, completely removing the 

 
  
  
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09-13-09c  CASE 3213  August1, 2017  V2.3  
technologist competence and patient cooperativeness pieces from the factors that affect exam 
quality. Preliminary data: The novel free-breathing high spatiotemporal resolution DCE liver 
MRI using non-Cartesian parallel imaging technique for quantitative perfusion mapping was 
performed on a Siemens 3T Skyra scanner with six subjects, including four healthy volunteers 
and two patients. A stack-of-spirals trajectory was under sampled in plane with a reduction factor 
of 6, and reconstructed using through-time non-Cartesian GRAPPA. High-resolution 3D images 
were acquired with a true temporal resolution of 1.6~1.9 seconds, while the subjects were 
breathing freely. A dual-input single-compartment model was established to retrieve liver 
perfusion parameters from DCE-MRI data, which were co-
registered using an algorithm designed to reduce the 
effects of dynamic contrast changes on registration 
performance.  
Results: Figure 1 shows representative under sampled and 
reconstructed images acquired from a normal subject at the 
arterial phase (~20 sec after contrast injection), portal 
phase (~70 sec) and equilibrium phase (~180 sec). With 
the automatic edge detection method, about 20-25% of the volumes from each subject were 
automatically detected by the algorithm to originate from the same position in the  
respiratory cycle, and thus pre-registered. After registering the remaining  
frames to the nearest “pre-registered” neighbor, almost no detectable solid organ motion  
remained. Figure 
2 
shows 
representative time 
courses of contrast 
concentration from 
the 
aorta, 
portal 
vein, and hepatic 
parenchyma (single 
voxel), and the model fit to the parenchymal time-course from a healthy subject. The time course 
from the liver voxel, same as before registration is also plotted as a comparison. The model fit 
after registration yielded an arterial fraction (AF), distribution volume (DV) and mean transit 
time (MTT) of 18.8%, 24.2%, and 4.6 s, respectively, while the same quantities prior to 
registration were 13.5%, 35.2%, and 10.6 s, respectively. The perfusion parameters after 
registration are all in good agreement with published literature for CT and MR (3,4,14).  
 Two patients were scanned (both with previous traditional scanning) with the developed 
technique as representative clinical examples. Patient 1 had biopsy proven metastatic breast 
adenocarcinoma, and Patient 2 had a biopsy proven sclerosing hemangioma that had 
demonstrated atypical imaging characteristics on traditional imaging. Perfusion modeling for 
patient 1 is shown in Fig. 3.   
AF, DV, and MTT were 
67.5%; 40.4%; and 99.8 s, 
respectively, for the lesion in 
Patient 1, all clearly different 
from surrounding parenchyma 
in the parametric maps.  

 
  
  
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09-13-09c  CASE 3213  August1, 2017  V2.3  
Similarly in Patient 2, the AF,  
DV and MTT were 99.4%, 21.0%, and 27.6 s, respectively, again different from surrounding 
tissue, and demonstrating nearly 100% arterial fraction as expected from hemangioma.   
  
2.0 OBJECTIVES  
We hypothesize that a quantitative and near free-breathing MRI approach will lead to improved 
tissue characterization, resulting in fewer ambiguous readings and thus fewer biopsies. As each 
component of the proposed methodology has been experimentally validated in our preliminary 
work, the next appropriate step would be to evaluate the clinical feasibility of the exam. Our 
goal is to test the ability of our developed quantitative MRI techniques to provide high 
quality images of the liver and to differentiate liver lesions from one another in a 
timeframe shorter than a current clinical exam.   
  
   
  
3.0 PATIENT/SAMPLE SELECTION  
We aim to scan at least 170 patients who are scheduled for liver intervention or MRI exam of the 
liver using the new quantitative protocol, assess the discrimination accuracy of binary classifiers 
in predicting lesion type, and compare the diagnostic accuracy of the new protocol to the clinical 
standard.  
  
4.0 REGISTRATION PROCEDURES   
If applicable, all patients enrolled on study will be entered into the Oncore database. If samples 
are being collected, a sample count will be entered into the database.  
 
5.0 RESEARCH PLAN   
Our abdominal imaging group performs at least 150-200 MRIs for liver lesions every year. A 
vast majority of these lesions are HCC or metastatic disease (approximately 40% each), a small 
number are cholangiocarcinoma (at most 10%) and an additional 10% are benign lesions such as 
adenomas, hemangiomas, or focal nodular hyperplasia (FNH). Most patients also undergo 
biopsies to establish diagnosis. For our analysis we will obtain a quantitative dataset of 170 focal  
liver lesions in which the biopsy or clinical "truth" is known.   
 
Inclusion Criteria:  
All patients scheduled for a MRI exam of the liver will be eligible to participate in this study.  
1. Patients with known liver lesion 
2. Male or female patients, age 18 to 100 years.  
3. No contraindications 
to 
getting contrast 
enhanced MRI 
examinations.  
4. GFR ≥ 40.  
The study population may include illiterate persons and UH/Case employees if they meet other 
inclusion criteria. The consent process for these potential participants will be conducted 
according to IRB guidelines.  
Exclusion Criteria:  
1. Patients with ferromagnetic or otherwise non-MRI compatible aneurysm clips.   
2. The presence of an implanted pacemaker or implanted defibrillator device  

 
  
  
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09-13-09c  CASE 3213  August1, 2017  V2.3  
3. Patients with contraindications for MRI due to embedded foreign metallic objects.  Bullets, 
shrapnel, metalwork fragments, or other metallic material adds unnecessary risk to the patient.  
4. Pregnancy. Regular clinical practice already excludes pregnant patients from gadolinium 
contrast due to unknown effects on the fetus. The current clinical practice will be applied - 
patients will be verbally screened and asked if they think they could be pregnant. If the answer 
is yes, then the patient will be excluded from the study. If the patient is uncertain about the 
pregnancy status, she will be given an option to undergo a pregnancy test or not participate in 
the study altogether. Patients who self-report that they are not pregnant will be allowed to 
participate in the study. This procedure is based on current department policy guidelines.  
5. Implanted medical device not described above that is not MRI-compatible;   
6. Known history of claustrophobia;   
7. Known history of allergic reaction to MR contrast material;   
8. Late stage renal failure with estimated glomerular filtration rate (eGFR) of less than 30 
mL/min/1.73 m2 based on patient's serum creatinine due to the significantly increased risk of 
nephrogenic systemic fibrosis (NSF). (‘Past’ 3 months timeframe will be used to calculate the 
eGRF).  
9. Minors will be excluded.  
10. Prisoners and members of other vulnerable populations will be excluded from this study.  
The subject selection population will not regularly include prisoners and other vulnerable 
population members as these populations will not provide any additional unique information to 
or uniquely benefit from the study. Non-english speaking population will be excluded from the 
study due to lack of sufficient resources to pay for translator and interpreter services.  
  
Recruitment procedures:  
There will be two methods of recruitment. The first method is via referral of patients from the 
intervention radiology clinic.  Secondly, we have a waiver of HIPAA authorization and waiver of 
consent to identify and contact patients from the out-patient schedule. 
 
The abdominal imaging section runs an intervention radiology clinic where patients with liver 
lesions are evaluated in order to plan and conduct the liver intervention procedure. All of the 
physicians at this intervention radiology clinic are co-investigators on the current IRB protocol 
and have physician-patient relationship with these clinic patients. Upon referral, a member of the 
research team will approach these patients in person during their pre-procedure evaluation visit 
and give them an option to participate in the research study. During this visit, the patients will be 
given information about the research study procedure. The patient will be conveyed the 
information regarding potential direct and indirect benefits, and risks and discomforts associated 
with the study. The patients will also be informed that there are no financial charges to them or 
their insurance for this research scan and that they will receive an amount of $100 as 
compensation for participation in the study. All communication with the patient will be 
conducted in a private area. All of the patient questions regarding the research study will be 
answered satisfactorily. If the patients wish to participate in the study, they will be consented on 
the same day (pre-procedure evaluation visit to the clinic) and will be scheduled for research 
MRI scan before the day of their intervention procedure. The patients will be offered a copy of 
the signed consent form to take home with them to discuss with their friends and family if they 
wish to. Only if the patient consents to participate in the research study during the first meeting 

  
  
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09-13-09c  CASE 3213  August1, 2017  V2.3  
and agrees to come in for research MRI in the future, then the study personnel will communicate 
with the patients by phone to confirm the appointment for research MRI and answer any 
questions the patient may have at this point. The referring physician/ primary care team will 
provide the diagnosis to the patients. The research team personnel will not provide any diagnosis 
to the patient.  
We have a waiver of HIPAA authorization and waiver of consent to identify and contact patients 
from the outpatient MRI schedule.  
 
Request for waiver of HIPAA authorization and waiver of consent: The investigator will take 
precautions to protect the subject’s privacy and the confidentiality of the data pertaining to 
his/her participation in this research study. We are requesting a waiver of HIPAA authorization 
and waiver of consent for contacting the patients in person and not the waiver of the consent for 
the research study as such. We intend to identify patients on outpatient MRI schedule for a 
clinically indicated liver MRI and contact them in person. The will be no improper use of or 
disclosure of PHI under this waiver. Only the research staff will access the PHI for above 
described purpose. The patient identifiers accessed under this waiver of HIPAA authorization 
will not be retained. The identifiers will be destroyed on the same day once the purpose of 
contacting the patients in person is complete. We assure that the PHI will not be reused or 
disclosed to (shared with) any other person or entity, except as required by law, for authorized 
oversight of the research study, or for other research for which the use or disclosure of the PHI 
would be permitted under the Privacy Rule. We are requesting a waiver of HIPAA authorization 
for contacting the patients in person and not a waiver of informed consent process for the study 
itself. The patients with benign lesions are typically not biopsied. It is imperative to include a 
cohort of such patients in the study to increase the diversity of study population and demonstrate 
the robustness of the new imaging technique. We will use the MRI schedule to identify potentially 
eligible subjects who are undergoing liver scans. For this purpose, the waiver of HIPAA 
authorization and waiver of consent is necessary for recruitment. We will not be able to meet our 
recruitment goals without this waiver, because there is no other way we can contact the patients 
with benign lesions scheduled for clinical MRI.  
 
 With the waiver of HIPAA authorization and waiver of consent, we will be able to use the MRI 
schedule to identify subjects who are undergoing liver scans on a given day. On the day of the 
scheduled clinical MRI exam we will approach the patient in person and give them brief 
information regarding the research study. The patient will be given information regarding 
potential direct and indirect benefits, and risks and discomforts associated with the study. The 
patients will be informed that there are no financial charges to them or their insurance for this 
research scan and that they will receive an amount of $100 as compensation for participation in 
the study.  We will ask the patient if he/she is interested in participating in the research MRI. We 
will request permission from the patient if he/she is willing to be contacted by phone for 
scheduling a research MRI scan in the future. We will explain it clearly to the patient that he/she 
will be contacted for participation only if he/she is deemed eligible to participate in the study 
after discussion with his/her referring physician/primary care team. Thus, the consent for 
contacting the patients for future participation in research MRI study will be obtained from the 
patients on the day of their scheduled clinical MRI when the research team member can meet the 
patient in person. The subjects will not be approached at their doctor’s visit.  The patients will be 

 
  
  
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09-13-09c  CASE 3213  August1, 2017  V2.3  
offered a copy of the informed consent form for the actual research MRI to take home with them 
to study and discuss with family/friends, if desired. All the communication and conversation 
with the patient will be conducted in a private area. For the research personnel to contact the 
patient in a manner that is suitable for them, we will ask the patient to provide their contact 
information (including phone number and/or email address). We will also ask the patients to 
specify which mode of communication is suitable for them and what time slot of the day is most 
acceptable if they choose to be contacted by phone.  Only if the patient consents to be contacted 
for research MRI in the future, then the study personnel will communicate with the eligible 
patients by phone to schedule the study and answer any questions the patient may have at this 
point 
 
 
If the patient has signed the consent to contact, we will call or email depending upon their 
preference to schedule the research scan. We will also ensure that the primary care team/ 
referring physician provides the diagnosis to the patients prior to being contacted by the research 
team for scheduling the research study in the following manner. If the patient consents to be 
contacted, about 3-5 days after the clinical MRI is done a member of the research team will 
communicate with the clinical care team member by phone or encrypted UH email and find out if 
the patient has received diagnosis for his liver problem from them. If the answer is no, we will 
repeat this process in another 3-5 days. If the answer is affirmative, then we will communicate 
with the patient by phone to schedule a research MRI study at his/her convenience.  
The research MRI consent form will be signed on the day the patient comes in for the research 
study, unless the patient decides not to participate. The consent procedure for the research study 
will be again conducted in a private area. All the patient’s questions will be answered 
satisfactorily. A copy of the signed informed consent will be offered to the patient for his/her 
record. The study population may include illiterate persons and UH/Case employees if they meet 
other inclusion criteria. The consent process for these potential participants will be conducted 
according to IRB guidelines. For illiterate individuals who may consider study participation, the 
consent form will be read out to the participant and the process will be documented in the 
research file. The participant will sign the consent form by making their mark in the signature 
section of the consent document in order to document their understanding. A witness will be 
present to confirm that the consent process has taken place. Both the witness and the person 
obtaining informed consent will sign and date the consent document. The UH/Case employees 
who may consider study participation will be informed that their participation in a study, or 
refusal to do so, will in no way influence their employment, or subsequent recommendations and 
that their job, promotion, salary, or status in any way depends on participation in research 
studies. Also they will be informed that refusal to participate will have no influence on 
recommendations or job status.  
In total, 170 subjects who meet inclusion criteria and who are willing to consent to participation 
in the study will be recruited.  
6.0 STUDY PARAMETERS  
MRI of liver using the proposed research technique will be performed on all study subjects. The 
imaging data will be utilized as a study parameter. This imaging data will be compared with 
clinical standard imaging and biopsy results of the patient.  
  

 
  
  
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09-13-09c  CASE 3213  August1, 2017  V2.3  
7.0  
CORRELATIVE STUDIES (if applicable)  
N/A  
  
8.0  
STATISTICAL CONSIDERATIONS  
Ten-fold cross-validation will be used to assess the discrimination accuracy of binary classifiers 
predicting HCC vs. benign lesions, metastases vs. benign lesions, or metastases vs. HCC [69]. 
We hypothesize that each classifier will predict non-benign lesions with accuracy (ROC curve 
area) of at least 80%. With 40 abnormal and 80 benign cases, a one-sided test at a significance 
level 0.05 testing the null hypothesis that the area under the ROC curve is an uninteresting level 
of 0.65 vs. the alternative that it is greater than 0.65 will achieve 91% power when the ROC 
curve area is 0.80 for the new classifier. For a binary classifier discriminating metastases vs. 
HCC, with 40 cases per group, the power is 84% to test that the area greater than 0.65, when the 
true ROC area is 0.80 (SAS macro ROCPOWER, 
http://www.bio.ri.ccf.org/doc/rocpower_help.txt).   
In a second step, the diagnostic accuracy of the quantitative protocol will be compared to the 
standard clinical exam. In each of the cases described above, the three radiologists will be asked 
to arrive at the most likely diagnosis, by consensus. The quantitative techniques will be similarly 
used to predict the most likely diagnosis for each lesion. Agreement between the quantitatively 
predicted “most likely diagnosis” and the actual diagnosis (categorized as HCC, other 
metastases, cholangiocarcinoma or benign/other) will be estimated and com-pared to the 
agreement between the clinical MRI-based diagnosis and true diagnosis using a McNemar test 
for correlated proportions. With the a sample size of 170, a difference in agreement proportions 
of 0.75 vs. 0.87 can be detected with 80% power with a two-sided 0.05 significance level test.  
 Funding for Statistical Analysis: Dr. Schluchter with perform the statistical analysis and the grant 
funding listed for this project covers his time.  
  
9.0  
RECORDS/DATA TO BE KEPT  
Records that will be kept by the investigators on each subject in the study include age and 
gender, clinical assessment, type of liver disease, co-morbidities, imaging as a part of standard of 
care, laboratory results, medications, allergies, MRI technical parameters (TR, TE, Matrix size, 
Coil used, flip angle, temporal resolution, slice thickness, FOV, number of slices, parallel 
imaging acceleration factor, total image acquisition time, total number of images), T1, T2, 
diffusion parameters, as well as perfusion data. These are primarily MR technical data recorded 
at the time of acquisition. The remainder of the information will be gathered from PACS, IDX 
and EMR.  
 
The investigator will take precautions to protect the subject’s privacy and the confidentiality of 
the data pertaining to his/her participation in this research study. In order to minimize the risk of 
loss of confidentiality, all records related to the study data will be kept in locked cabinets. The 
imaging data will be de-identified and stored and a linking sheet will be created. Access to study 
information and documents will be restricted to research personnel.  A password system will be 
used to control access to all information stored on a secured computer. All reports, forms, or 
articles related to this study will be prepared such that no individual patient can be identified.  No 
data that can be linked to the subject will be entered into a network computer that could allow 
access to confidential information.  All data entered into the computer will be coded and personal 

 
  
  
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09-13-09c  CASE 3213  August1, 2017  V2.3  
identifiers will be removed.  The master list will be stored off-line and will be available only to 
the principal investigator or his designee(s).  The data will be stored until three years after last 
publication of the results, at which time they will be destroyed/deleted.  
 
Data Safety Monitoring Plan:  
The group of investigators, including the principal investigator, and the research support staff 
will carry out the Data and Safety Monitoring Plan.  Adverse events will not be submitted to an 
external Data and Safety Monitoring Board or Committee for assessment; instead, there will be 
an ongoing review of the aggregate data each month to ensure that the study can continue 
without undue risk to participants.  Data will be reviewed to ensure that they are accurate, 
complete, and that data collection is in compliance with the protocol.    
 
Risks to patients in this study include all those risks currently associated with standard contrast 
enhanced MRI. These include discomfort involved with being required to lie still in a small 
space; and possibly risks that are unknown at this time. These risks are all considered rare (likely 
occurring in fewer than 10 of every 100 patients). Patients with severe renal dysfunction 
(GFR<30) are at risk of nephrogenic systemic fibrosis (NSF). Due to this risk, patients with GFR 
below 40 will be excluded from the study. This threshold is considerably higher than the current 
clinical threshold of GFR below 30.  Very small amounts of MRI contrast agents deposit in 
certain tissues of the body including regions of the brain, in patients who have received multiple 
doses of these agents. No known harm has been associated with the deposition, before or since 
the description of this deposition in 2014. More than 300 million doses of gadolinium contrast 
have been given in humans since their first use.71. 
 
Identification of subjects with severe renal dysfunction: The subjects with severe renal function 
will be identified as follows. The subjects in both sets will undergo a clinical MRI study for 
evaluation of liver lesion before being recruited in the research study. As a result, they will be 
evaluated for the status of their renal function before the clinical MRI scan. The research team 
will access their renal parameters after acquiring consent for study participation in the ‘biopsy 
set’ and consent to contact in the ‘benign lesion set’. Although an eGFR cut off of 30 
mL/min/1.73 m2 is used for clinical MRI, patients with eGFR below 40 mL/min/1.73 m2 will 
not be included in the study for additional safety. Additionally, before undergoing research MRI, 
every participant will fill up the standard clinical MRI safety screening sheet which asks the 
patient about any current or previous renal problems.   
The risks expected from participation in this study are minimal and usually are not serious. 
However, any subject who experiences problems from participating in this study will be 
provided all appropriate medical care.  All patients will be otherwise followed according to 
standard of care. The group of investigators, including the principal investigator and the research 
support staff will carry out the Data and Safety Monitoring Plan. Adverse events will not be 
submitted to an external Data and Safety Monitoring Board or Committee for assessment; 
instead, there will be an ongoing review of the aggregate data each month to ensure that the 
study can continue without undue risk to participants. Data will be reviewed to ensure that they 
are accurate, complete, and that data collection is in compliance with the protocol.   
 

 
  
  
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There will also be a continual assessment of the risks and benefits through the review of 
individual adverse events and other safety parameters as they occur throughout the study to 
determine whether individual participants can safely continue to participate.   Serious adverse 
events, should any occur, will be reviewed within 48 hours of occurrence with a determination 
made for medically appropriate follow-up for the subject involved.  Adverse event reporting will 
be strictly performed in compliance with IRB rules for reporting.  
  
10.0  
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