Dotarem Evaluation for Myocardial Perfusion CMR
Conditions: Myocardial Perfusion Imaging, Magnetic Resonance Imaging
Sponsor: Medical University of South Carolina

 
1 
Version Date: 10.24.2018 
Clinical Study Protocol 
 
 
 
Dotarem® for Myocardial Perfusion Cardiovascular Magnetic Resonance 
 
 
 
 
Principal Investigators:   
U. Joseph Schoepf, MD 
 
 
 
 
Medical University of South Carolina 
Department of Radiology and Radiological Science 
25 Courtenay Drive 
Charleston, SC29425 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CONFIDENTIALITY STATEMENT 
 
This document is the confidential property of Medical University of South Carolina, Radiology 
Department.  No Part of it may be transmitted, reproduced, published or used by other persons 
without the permission of the Principal Investigator. 
 
 

 
2 
Version Date: 10.24.2018 
 
 
 
 
 
Dotarem® Evaluation for Myocardial Perfusion Cardiovascular Magnetic 
Resonance 
 
Table of Contents 
A.  SPECIFIC AIMS 
3 
B.  BACKGROUND AND SIGNIFICANCE 
3 
C.  PRELIMINARY STUDIES 
3 
D.  RESEARCH DESIGN AND METHODS (including data analysis) 
4 
D.1  Image acquisition 
4 
D.2  Image analysis 
5 
D.3 
Statistical Methods / Sample Size Justification 
5 
E.  PROTECTION OF HUMAN SUBJECTS 
5 
E.1 
RISK TO THE SUBJECTS 
5 
E.1.a  Human Subject Involvement and Characteristics 
5 
E.1.b Sources of Materials 
7 
E.1.c Potential Risks 
7 
E.2   ADEQUACY OF PROTECTION AGAINST RISKS 
8 
E.2.a   Recruitment and Informed Consent 
8 
E.2.b  Protection against Risk 
9 
E.3  
POTENTIAL BENEFITS OF THE PROPOSED RESEARCH TO THE SUBJECTS AND OTHERS 
9 
E. 4  IMPORTANCE OF THE KNOWLEDGE TO BE GAINED 
9 
E.5  
SUBJECT SAFETY AND MINIMIZING RISKS (Data and Safety Monitoring Plan) 
10 
F. FACILITIES AVAILABLE 
10 
G.  REFERENCES 
10 
Medical University of South Carolina 

 
3 
Version Date: 10.24.2018 
A.  SPECIFIC AIMS 
The overall goal of this study is to investigate the signal intensity and relaxation rate characteristics of 
gadoterate meglumine (Dotarem, Guerbet, USA) enhanced myocardium during rest and stress 
perfusion cardiovascular magnetic resonance (CMR) compared to gadobutrol (Gadavsit) to prove that 
Dotarem provides constantly high myocardial relaxation necessary for accurate quantitative perfusion 
evaluation. Within this overall goal, the following specific aims will be pursued:  
 
Aim 1: To test the hypothesis that the signal intensity enhancement during Dotarem 
myocardial stress/rest perfusion is relatively constant, providing linear and stable 
enhancement in the myocardium, and is not inferior compared to gadobutrol (Gadavist). 
 
Aim 2: To test the hypothesis that the relaxation rate enhancement during Dotarem 
myocardial rest perfusion is uniform in the myocardium. 
 
B.  BACKGROUND AND SIGNIFICANCE 
Stress perfusion imaging is indicated in symptomatic patients suspected of coronary artery disease 
(CAD) with low or intermediate cardiovascular risk and typical/atypical chest pain or angina-equivalent 
symptoms, as well as in asymptomatic patients with high cardiovascular risk profiles, such as diabetics, 
or in patients with known CAD during follow-up.1 Myocardial perfusion by CMR was introduced 
approximately two decades ago.2 Compared with SPECT, which uses a radioisotope that is actively 
taken up by the myocytes to depict myocardial perfusion, CMR evaluates the first pass of an 
extracellular contrast agent (CA) within the myocardium. Whereas the stress protocol used for both 
methods is similar, CMR offers the benefit of superior spatial and temporal resolution, and SPECT is 
associated with the negative effects of exposure to ionizing radiation.3, 4 Although, several studies 
proved that stress perfusion CMR outperforms stress perfusion SPECT5-7, the quantitative evaluation 
of myocardial blood flow by CMR is still a challenging topic due to, for example, the non-linear signal 
intensity changes and the different relaxation rate enhancements caused by the various gadolinium-
based CAs8-10, representing a major limitation to the widespread use of the technique in clinical 
practice.  
Dotarem, a macrocyclic agent with fast clearance kinetics, has the highest thermodynamic stability 
among the currently approved clinical contrast agents.11 This high stability is due to its molecular 
structure, which provides a significantly reduced dissociation rate (i.e. Release of free gadolinium ions) 
compared to other agents.11 While the in vitro relaxivity (3.4 mm-1s-1)12 of Dotarem is comparable to 
other agents, we suggest that its high stability and extremely low dissociation rate provide constant 
signal intensity and relaxation rate enhancement during myocardial perfusion CMR, improving the 
accuracy and reliability of quantitative perfusion analysis. 
The efficacy of Dotarem enhanced late gadolinium enhancement (LGE) imaging has been investigated 
and compared to gadobutrol (Gadavist, Bayer, Germany) to visualize and quantify myocardial scar.13 
However, a similar comparison for the assessment of myocardial ischemia by CMR myocardial 
perfusion – an even more crucial step in a clinical CMR protocol – would further strengthen the value 
of Dotarem in cardiovascular imaging. While LGE is able to visualize irreversible myocardial injury, 
myocardial perfusion imaging has the ability to depict reversible ischemia that can potentially be 
treated by coronary intervention. 
 
C.  PRELIMINARY STUDIES 
Our research group consists of clinical and research faculty who have extensive experience and a 
substantial publication record related to contrast enhanced cardiac MRI and contrast agent 
characterization.14-18 In a previous research project, our team developed an image analysis technique 
(detailed in Section D) that we will use in Aim 2 to investigate the relaxation profile of Dotarem.16  

 
4 
Version Date: 10.24.2018 
 
D.  RESEARCH DESIGN AND METHODS (INCLUDING DATA ANALYSIS)  
D.1  IMAGE ACQUISITION 
This prospective study will include a total of 90 patients (Aim 1 + Aim 2) who present to the MUSC 
Radiology Department for a clinically indicated cardiac MRI scan over a 2-year period. Patients will be 
imaged using a state of the art 1.5T scanner (MAGNETOM Avanto, Siemens Healthcare, Erlangen, 
Germany) system.  
Aim 1: In this specific aim, a total of 60 patients referred for a clinically indicated stress myocardial 
perfusion MRI scan out of concern of suspected myocardial ischemia will be included. Patients will be 
scanned using a standard clinical contrast-enhanced stress perfusion protocol (regadenoson 0.4mg 
bolus) detailed in Figure 1. Patients will be randomized into two groups prior to patient consenting: 
Group 1 (n=30) will receive the clinically approved gadoterate meglumine (Dotarem, 0.1mmol/kg) as 
contrast agent for their clinical perfusion study, while Group 2 (n=30) will receive the clinically 
approved gadobutrol (Gadavist, 0.1mmol/kg) as contrast agent. The contrast agents will be 
administered at a flow rate of 5.0 ml/s for both groups. In this study aim, all imaging protocols will 
comply with standard of care and only the perfusion data will be post-processed and analyzed. 
Aim 2: In this specific aim, a total of 30 patients referred for a clinically indicated contrast enhanced 
cardiac MRI will be included. These patients will undergo a clinical viability cardiac MRI protocol with 
the administration of gadoterate meglumine (Dotarem, 0.1mmol/kg), except that a prototype MRI T1 
mapping pulse sequence will be used to acquire equilibrium T1 maps during the first pass of the 
contrast agent. This first pass perfusion step will be performed in rest, no stress agent will be 
administered. The rest perfusion acquisition is part of the standard protocol, however, we will use this 
prototype pulse sequence for research purposes.  
 
Figure 1 – MRI protocols 
 

 
5 
Version Date: 10.24.2018 
D.2  IMAGE ANALYSIS 
In Aim 1, we will generate signal intensity-time curves from the perfusion data and evaluate the 
characteristics of signal intensity changes and absolute myocardial blood flow using the MASS 
Research Software (LUMC, Leiden, Netherlands). The signal characteristics will be compared between 
the two contrast groups. Image quality will also be subjectively rated by multiple independent 
observers.  
In Aim 2, we will generate equilibrium T1 maps based on the pre-contrast T1 and repeated inversion 
recovery images during the perfusion of the CA. This technique allows the calculation of the post-
contrast T1 at every phase during the first-pass perfusion of the CA. The uniformity of T1 and R1 
(inverse T1) will be evaluated using the MASS Research Software. 
 
D.3 
STATISTICAL METHODS / SAMPLE SIZE JUSTIFICATION 
All analyses and graphs will be performed by using commercially available software (MedCalc version 
12.7.2; SPSS version 21). Descriptive statistics will be provided as mean ± standard deviation (SD) for 
continuous variables and absolute and relative frequencies for categorical variables. Normal data 
distribution will be assessed with a Kolmogorov-Smirnov test. For each group, comparisons of patient 
characteristics will be performed by using the χ² test for categorical variables and t-test or Mann-
Whitney-U-test for continuous variables as appropriate. Subjective image quality scores will be 
compared using  the χ² test with the Yates continuity correction for categorical variables and inter-
observer agreement for image quality will be calculated using Cohen kappa statistics and interpreted 
as follows: ≤0.20 slight or poor agreement, 0.20–0.40 fair agreement, 0.40–0.80 moderate agreement, 
≥0.80 excellent agreement. 
 
E.  PROTECTION OF HUMAN SUBJECTS 
E.1 
RISK TO THE SUBJECTS 
E.1.a  Human Subject Involvement and Characteristics 
 
Aim 1 
Inclusion criteria: 
To be eligible for the study: (All answers must be “YES” for subject to be eligible.) 
1. Subject must be referred for a clinically indicated contrast-enhanced stress myocardial 
perfusion MRI scan out of concern of suspected myocardial ischemia.  
2. Subject must be older than 18 years of age. 
3. Subject must provide written informed consent prior to any study-related procedures being 
performed.  
4. Subject must be willing to comply with all clinical study procedures. 
 
Exclusion Criteria: 
The presence of the following excludes subjects from the study: (All answers must be “NO” for 
subject to be eligible.) 
1. Subject is a pregnant or nursing female. Exclude the possibility of pregnancy: 
- 
By testing (serum or urine beta HCG) within 24 hours before study date, or 
- 
By surgical sterilization, or 
- 
Post-menopausal, with minimum one (1) year history without menses. 
2. Subject has an implanted cardiac pacemaker or implantable defibrillator. 
3. Subject has a ferromagnetic vascular clip. 
4. Subject has a neurostimulation system (e.g. TENS-Unit). 

 
6 
Version Date: 10.24.2018 
5. Subject has any type of cochlear implant. 
6. Subject has ocular foreign body (e.g. metal shavings). 
7. Subject carries any implanted device (e.g. insulin pump, drug infusion device). 
8. Subject has shrapnel, bullet, or other type of metal fragments within the body. 
9. Subject has an acute psychiatric disorder or is cognitively impaired. 
10. Subject is using or is dependent on substances of abuse. 
11. Subject is unwilling to comply with the requirements of the protocol. 
12. Subject is in acute unstable condition. 
13. Subject has an allergy against gadolinium based contrast agents or pharmaceutical stressors 
used in this study. 
14. Subject has impaired renal function (creatinine > 1.5 mg/dl). 
15. Subject presenting with acute coronary syndrome. 
16. Positive cardiac enzymes positive troponin, CK-MB, or myosin 
17. ST-elevations, new transient ST changes greater than 0.05mV or T- wave inversions with 
symptoms 
 
Aim 2 
Inclusion criteria: 
To be eligible for the study: (All answers must be “YES” for subject to be eligible.) 
1. Subject must be referred for a clinically indicated contrast-enhanced stress myocardial 
perfusion MRI scan out of concern of suspected myocardial ischemia.  
2. Subject must be older than 18 years of age. 
3. Subject must provide written informed consent prior to any study-related procedures being 
performed.  
4. Subject must be willing to comply with all clinical study procedures. 
 
Exclusion Criteria: 
The presence of the following excludes subjects from the study: (All answers must be “NO” for 
subject to be eligible.) 
1. Subject is a pregnant or nursing female. Exclude the possibility of pregnancy: 
- 
By testing (serum or urine beta HCG) within 24 hours before study date, or 
- 
By surgical sterilization, or 
- 
Post-menopausal, with minimum one (1) year history without menses. 
2. Subject has an implanted cardiac pacemaker or implantable defibrillator. 
3. Subject has a ferromagnetic vascular clip. 
4. Subject has a neurostimulation system (e.g. TENS-Unit). 
5. Subject has any type of cochlear implant. 
6. Subject has ocular foreign body (e.g. metal shavings). 
7. Subject carries any implanted device (e.g. insulin pump, drug infusion device). 
8. Subject has shrapnel, bullet, or other type of metal fragments within the body. 
9. Subject has an acute psychiatric disorder or is cognitively impaired. 
10. Subject is using or is dependent on substances of abuse. 
11. Subject is unwilling to comply with the requirements of the protocol. 
12. Subject is in acute unstable condition. 
13. Subject has an allergy against gadolinium based contrast agents used in this study. 
14. Subject has impaired renal function (creatinine > 1.5 mg/dl). 
 
There will not be any eligibility criteria for any subpopulations. In addition, there will not be any 
targeted involvement of special classes of subjects, such as fetuses, neonates, pregnant women, 

 
7 
Version Date: 10.24.2018 
children, prisoners, institutionalized individuals, or others who may be considered vulnerable 
populations. All race and ethnicities and both genders will be considered for inclusion into the study. 
Subjects under the age of 18 will not be considered for inclusion into this study.  
 
Targeted/Planned Enrollment Table 
 
Total Planned Enrollment: 90 (Aims 1 and 2 combined) 
 
Table 1: Targeted/planned enrollment (number of subjects). 
Ethnic Category 
Sex/Gender 
Females 
Males 
Total 
Hispanic or Latino 
3 
3 
6 
Not Hispanic or Latino 
42 
42 
90 
Ethnic Category: Total of All Subjects 
90 
Racial Categories 
 
American Indian/Alaska Native 
0 
0 
0 
Asian 
1 
1 
2 
Native Hawaiian or Other Pacific Islander 
0 
0 
0 
Black or African American 
12 
12 
24 
White 
32 
32 
64 
Racial Categories: Total of All Subjects 
45 
45 
90 
 
 
E.1.b Sources of Materials 
The research materials that will be obtained from living human subjects are: the MR images, report, 
injection report, progress notes, medication records, vital signs, medical history and demographics, 
and all other applicable clinical information.   
 
The Principal Investigator, Sub-Investigator(s) and the Study Coordinator(s) will be the only personnel 
who will have access to subject identities, with the exception of any regulatory personnel (MUSC IRB 
auditors, etc.). All subject identities will be removed prior to publication. 
 
Contrast and Drug Management 
Contrast agents (Dotarem and Gadavist) and stress agent (Regadenoson) will be ordered and 
dispensed from the MUSC inpatient pharmacy per clinical protocol. 
 
 
E.1.c Potential Risks 
Vein puncture 
Patients could experience bruising, pain, and rare incidence of infection at the vein puncture site. This 
is like a blood test. This puncture is used to inject the contrast agents. Care will be taken to avoid these 
possible risks. Skin or vein irritation, fainting, blood clot formation, bleeding at the injection site, or an 
infection could also occur. 
 
Adverse reactions caused by gadolinium contrast agent 
Gadolinium contrast agent will be administered as part of the clinical protocol, independently from the 
research component of the study. The research protocol will not increase the risk of contrast related 
adverse reactions in any of the research aims. Despite excluding patients with known history of allergy 

 
8 
Version Date: 10.24.2018 
to gadolinium-based contrast material, there is a small risk that a patient will have an allergic reaction 
to contrast medium. In this event, the attending physician supervising the MRI acquisition in the study 
will administer appropriate care. In patients with pre-existing renal dysfunction, gadolinium-based 
contrast material may cause further deterioration in renal function. Therefore, patients with decreased 
renal function (more than 1.50 mg/dL serum creatinine) will be excluded from this study.  
 
Risks from Contrast Agent Extravasation 
Although extremely rare, it is possible that an IV needle is not properly located within the vein or 
becomes dislodged when the patient lies down on the examination table. When contrast material is 
injected, it may then leak into the surrounding tissue. This can be painful and in very few instances has 
been reported to cause pressure on underlying nerves or vessels that needs to be surgically relieved. 
Usually, however, a contrast media extravasation is noticed early on by the personnel monitoring the 
procedure. However, even if a full dose of contrast material is injected in the tissue surrounding a vein, 
permanent damage is extremely unlikely. Usually the contrast material is fully absorbed by the body 
within a day without any harmful effect. In addition, in our department we use the latest automated 
contrast media injector generation, which also comprises of an automated extravasation detection 
device attached to the arm of the patient. Since the implementation of this device we have not 
experienced any major extravasation of contrast material. 
 
Adverse reactions caused by stress agent administration 
The following reactions are listed as warnings and precautions when using regadenoson (Lexiscan): 
Myocardial ischemia, sinoatrial and atrioventricular nodal block, hypotension, bronchoconstriction. 
The following adverse reactions associated with regadenoson are considered transient and are listed 
in the package insert: dyspnea or urge to breathe deeply, headache, flushing, chest discomfort, angina 
pectoris or ST segment depression, lightheadedness/dizziness, chest pain, nausea, abdominal 
discomfort, impaired taste, feeling hot. In addition, dyspnea can occur during stress myocardial 
perfusion imaging with associated arrhythmias such as hypoxia induced bundle branch block. The first 
signs of these rare side effects will cause the termination of the examination. Note, that stress agent 
will not be administered for research purposes.  
 
Risk of metal objects in the body 
Patients may suffer bodily harm in the course of the MRA examination from having metal objects in 
their clothing, from metal implants (e.g. pacemaker, implanted defibrillator, cochlear implants, 
cerebral aneurysm clips), or any other metal within the body (shrapnel, bullet or metal fragments). 
Before patients undergo the procedure, they will be prompted to take out any metal objects. Patients 
will be asked a series of detailed questions about any metal that they may have their body. 
 
Acquisition of patient information 
The risks associated with gathering this information are believed to be very low. This information will 
be stored on a password-protected computer and network server and in a locked office (ART Cardiac 
Imaging Research Office). The data from this study will be accessible only to the team of researchers 
from this application. 
 
E.2   ADEQUACY OF PROTECTION AGAINST RISKS  
E.2.a   Recruitment and Informed Consent 
Patients who have been referred for a stress myocardial perfusion MRI (Aim 1) or myocardial viability 
MRI (Aim 2) as part of a standard clinical evaluation determined by the treating physician(s) will be 
eligible for the study and recruited from the MUSC MRI schedule. The MRI technologist or member of 
the nursing staff will speak with potential subjects to ensure their willingness to be approached by a 
member of the research team. Willing patients will be approached and will undergo the informed 

 
9 
Version Date: 10.24.2018 
consent process. Consented subjects will undergo their clinically indicated MRI using the standard 
stress protocol (Aim 1) or the modified viability protocol (Aim 2).  
 
Patients will be screened by approved study personnel from the MUSC MRI schedule under a HIPAA 
waiver.  Study eligibility determination and study enrollment will be assessed and performed by and 
investigator in concert with a study coordinator delegated by the PI and approved by the IRB as being 
authorized to obtain informed consent.  
 
The PI, Sub-I(s) or the Study Coordinator(s) will obtain informed consent prior to enrollment into the 
study. The subject will be taken to a quiet/private area (which may include the scanning room, the 
patient bays or other private areas) and the study purpose, procedures, duration, risks/discomforts, 
benefits, alternatives, new information procedures and privacy statements will be explained to the 
subject. 
 
The subject will be asked to verbally repeat pertinent study information to ensure subject understands 
the nature of the research. Subjects will be provided the opportunity to ask any questions they may 
have. Consent will be documented in the currently IRB approved version of the informed consent and 
will be signed and dated by the person obtaining informed consent and the subject. 
 
E.2.b  Protection against Risk 
To minimize the risk of post-contrast nephropathy, patients with decreased renal function (creatinine 
>1.5 mg/dL) will not be eligible for this study. To minimize the risk of allergic reactions to gadolinium 
contrast material, patients with a history of allergic reactions to gadolinium contrast material will also 
be excluded.  
 
All subjects’ medical records will be confined in the usual medical health information office according 
to their policies and procedures. Each staff member that has approved access to electronic medical 
records will be given their own password and will be instructed not to reveal that password to anyone 
else. In addition, those copies of subject information utilized for the research protocol will be kept 
locked in the Radiology Research suite (ART 2244) in a research specific folder that will identify the 
subject on the outside of the folder only by initials, subject code (subsequent subject identifiers, i.e. 
001, 002, 003, etc., this number will not be able to identify the subject), protocol name, and IRB study 
number (Pro #). Any data that are used in publication, analyses, etc. will not identify the subject by 
name, etc. Subjects will be monitored in clinic as per clinical standard practice for any possible side 
effects and treated as indicated. 
 
E.3  
POTENTIAL BENEFITS OF THE PROPOSED RESEARCH TO THE SUBJECTS AND OTHERS 
The subjects whose data, documents, and records will be reviewed are not likely to receive any benefit 
from the proposed research. However, the quantitative and qualitative evaluation of myocardial 
perfusion has an important role in patient diagnosis, therapy and prognosis. The improved and more 
reliable detection of myocardial perfusion defects may provide faster diagnosis and better patient 
management, as well as avoid unnecessary tests (including invasive procedures and radiation 
exposure). As of today, Dotarem is the only gadolinium-based contrast agent without any reported 
nephrogenic systemic fibrosis case. Broadening the clinical use of Dotarem towards the cardiac MRI 
field would provide substantial benefit to patients, especially those who suffer from pre-existing renal 
disease.  
 
E. 4  IMPORTANCE OF THE KNOWLEDGE TO BE GAINED 
Clinical stress myocardial perfusion MRI is a contrast enhanced acquisition that requires the 
administration of gadolinium-based contrast agent. Currently, there is no FDA label exist for such 

 
10 
Version Date: 10.24.2018 
applications, thus all the clinical contrast-enhanced cardiac MRI scans are performed off-label. This 
study will further strengthen the evidence that such clinical indication is warranted and will also 
demonstrate that Dotarem is a suitable agent to provide diagnostics perfusion data. 
 
E.5  
SUBJECT SAFETY AND MINIMIZING RISKS (DATA AND SAFETY MONITORING PLAN) 
Eligibility in each case will be confirmed by a named investigator. The source data will be collected by 
an independent technician and/or study coordinator, maintained securely by the PI and checked by 
the named investigators. Clinical data will be recorded on a Case Report Form (CRF). However, formal 
monitoring of site records will not be completed as part of the general conduct of the study. Data 
collected will be authentic, accurate and complete and the study will be conducted in accordance with 
the currently approved protocol (and any future approved amendments), Good Clinical Practiced (GCP) 
and all applicable regulatory requirements.   
 
Any event meeting the criteria of an unanticipated problem involving risks to subjects or others will be 
reported to the MUSC IRB, as required by HRPP 4.7- Unanticipated Problems and Adverse Events Policy 
and Procedures. Clinical data will not be monitored by a 3rd party (i.e. Contract Research Organization) 
or sponsor but the results of the study will be written as a paper and may be submitted as abstracts to 
various conferences. Every effort will be made to ensure patient safety and confidentiality.  
 
F. FACILITIES AVAILABLE 
The Radiology department on the 2nd floor of the Ashley River Tower houses the MAGNETOM™ Avanto 
on which the MRI will occur. Nursing and physician preparation and monitoring of the patient, 
including the serum creatinine test, will occur in the patient bays of the Radiology department.   
 
G.  REFERENCES  
1. 
Gibbons RJ, Balady GJ, Bricker JT, et al. ACC/AHA 2002 guideline update for exercise testing: 
summary article. A report of the American College of Cardiology/American Heart Association 
Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). 
J Am Coll Cardiol. 2002;40:1531-1540 
2. 
Atkinson DJ, Burstein D, Edelman RR. First-pass cardiac perfusion: evaluation with ultrafast MR 
imaging. Radiology. 1990;174:757-762 
3. 
Gerber BL, Raman SV, Nayak K, et al. Myocardial first-pass perfusion cardiovascular magnetic 
resonance: history, theory, and current state of the art. J Cardiovasc Magn Reson. 2008;10:18 
4. 
Gerber TC, Carr JJ, Arai AE, et al. Ionizing radiation in cardiac imaging: a science advisory from 
the American Heart Association Committee on Cardiac Imaging of the Council on Clinical 
Cardiology and Committee on Cardiovascular Imaging and Intervention of the Council on 
Cardiovascular Radiology and Intervention. Circulation. 2009;119:1056-1065 
5. 
Schwitter J, Wacker CM, Wilke N, et al. MR-IMPACT II: Magnetic Resonance Imaging for 
Myocardial Perfusion Assessment in Coronary artery disease Trial: perfusion-cardiac magnetic 
resonance vs. single-photon emission computed tomography for the detection of coronary 
artery disease: a comparative multicentre, multivendor trial. Eur Heart J. 2013;34:775-781 
6. 
Schwitter J, Wacker CM, van Rossum AC, et al. MR-IMPACT: comparison of perfusion-cardiac 
magnetic resonance with single-photon emission computed tomography for the detection of 
coronary artery disease in a multicentre, multivendor, randomized trial. Eur Heart J. 
2008;29:480-489 
7. 
Greenwood JP, Motwani M, Maredia N, et al. Comparison of cardiovascular magnetic 
resonance and single-photon emission computed tomography in women with suspected 
coronary artery disease from the Clinical Evaluation of Magnetic Resonance Imaging in 
Coronary Heart Disease (CE-MARC) Trial. Circulation. 2014;129:1129-1138 

 
11 
Version Date: 10.24.2018 
8. 
Hsu LY, Groves DW, Aletras AH, et al. A quantitative pixel-wise measurement of myocardial 
blood flow by contrast-enhanced first-pass CMR perfusion imaging: microsphere validation in 
dogs and feasibility study in humans. JACC Cardiovasc Imaging. 2012;5:154-166 
9. 
Hsu LY, Kellman P, Arai AE. Nonlinear myocardial signal intensity correction improves 
quantification of contrast-enhanced first-pass MR perfusion in humans. J Magn Reson 
Imaging. 2008;27:793-801 
10. 
Shen Y, Goerner FL, Snyder C, et al. T1 relaxivities of gadolinium-based magnetic resonance 
contrast agents in human whole blood at 1.5, 3, and 7 T. Invest Radiol. 2015;50:330-338 
11. 
Rofsky NM, Sherry AD, Lenkinski RE. Nephrogenic systemic fibrosis: a chemical perspective. 
Radiology. 2008;247:608-612 
12. 
Canet Soulas EP, Marchand B, Casali C, et al. Evaluation of MR contrast agents with high 
relaxivity and reduced interstitial diffusion for contrast material-enhanced MRA and 
myocardial perfusion studies. Acad Radiol. 2002;9 Suppl 1:S88-91 
13. 
Rahsepar AA, Ghasemiesfe A, Suwa K, et al. Detection of Myocardial Scar by Late Gadolinium 
Enhancement Cardiac MR using Gafoterate Meglumine. RSNA. 2017:SSQ03-04 
14. 
Kiss P, Suranyi P, Simor T, et al. In vivo R1-enhancement mapping of canine myocardium using 
ceMRI with Gd(ABE-DTTA) in an acute ischemia-reperfusion model. J Magn Reson Imaging. 
2006;24:571-579 
15. 
Muscogiuri G, Rehwald WG, Schoepf UJ, et al. T(Rho) and magnetization transfer and INvErsion 
recovery (TRAMINER)-prepared imaging: A novel contrast-enhanced flow-independent dark-
blood technique for the evaluation of myocardial late gadolinium enhancement in patients 
with myocardial infarction. J Magn Reson Imaging. 2017;45:1429-1437 
16. 
Suranyi P, Kiss P, Ruzsics B, et al. Equilibrium signal intensity mapping, an MRI method for fast 
mapping of longitudinal relaxation rates and for image enhancement. Magn Reson Imaging. 
2007;25:641-651 
17. 
Varga-Szemes A, Kiss P, Rab A, et al. In Vitro Longitudinal Relaxivity Profile of Gd(ABE-DTTA), 
an Investigational Magnetic Resonance Imaging Contrast Agent. PLoS One. 2016;11:e0149260 
18. 
Varga-Szemes A, van der Geest RJ, Spottiswoode BS, et al. Myocardial Late Gadolinium 
Enhancement: Accuracy of T1 Mapping-based Synthetic Inversion-Recovery Imaging. 
Radiology. 2016;278:374-382