Utility of MRI With Doppler Ultrasound Gating for Advanced Fetal Monitoring
Phase: NA
Conditions: Congenital Heart Disease
Sponsor: The Hospital for Sick Children

September 19, 2019 
 
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Study Protocol 
Title:  
Utility of MRI with ultrasound gating for advanced fetal monitoring  
Institution: 
This Hospital for Sick Children 
 
Team Members 
Principal Investigator:  Dr. Chris Macgowan (Imaging Scientist; SickKids) 
Qualified Investigator: Dr. Mike Seed (Cardiologist; SickKids) 
Research Coordinator: Anjana Ravi Chandran (Research Coordinator; SickKids) 
Co-investigators: 
Dr. Fabian Kording (Scientist; University Medical Centre Hamburg-Eppendorf) 
Dr. Greg Stortz (Research Analyst; SickKids) 
Dr. Eric Schrauben (Postdoctoral Fellow; SickKids) 
Christopher Huynh (Ph.D. Student; University of Toronto) 
Datta Goolaub (Ph.D. Student; University of Toronto) 
 
 
Study Period: 
1 year  
 
BACKGROUND AND SIGNIFICANCE 
 
Abstract 
This is a pilot study involving simultaneous magnetic resonance imaging (MRI) and ultrasound in 
pregnant participants with fetal congenital heart disease. The aim of this research study is to integrate 
non-imaging Doppler ultrasound to provide fetal cardiac gating during the MRI acquisition. This aim 
encompasses making clear images of the fetal heart and blood vessels, and reproducible measurements 
of fetal blood flow. MRI-derived blood flow waveforms in the fetus and anatomical images of the fetal 
heart will be compared with those from diagnostic ultrasound for validation.  
 
Rationale 
Fetal MRI can be used in adjunct to conventional obstetric ultrasound to assess and monitor the health 
of the fetus in the case of complicated pregnancies. For example, once the fetus is diagnosed with 
congenital heart disease (CHD) through initial ultrasound screening, the patients may be referred to our 
MRI program for additional fetal cardiovascular assessment. We would like to develop and apply MRI for 
advanced fetal cardiovascular assessment to better manage complicated pregnancies with the intent to 
improve patient care and postnatal health outcomes. Results from MRI may aid in the guidance of fetal 
interventions, managing optimal timing of delivery and planning for post-natal care. 
 
Our group has studied the fetal circulation in healthy pregnancies and in the settings of CHD and 
intrauterine growth restriction (IUGR) [1]. Despite our early successes in studying the fetal heart and 
circulation by MRI, such studies have been limited by practical challenges including the small size of fetal 
structures, the high fetal heart rate and unpredictable motion of the fetus. For example, in late 
gestation the diameter of a normal left ventricle is only 15 mm and major vessels are even smaller with 
diameters less than 8 mm [2]. These small dimensions coupled with high heart rates (between 110-180 
bpm) necessitate high spatial and temporal resolutions to capture cardiac dynamics [3].  
 
To address these limitations, state-of-the-art MRI techniques originally designed for evaluating the adult 
heart must be translated to fetal imaging [4]. Phase contrast (PC) MRI is the gold standard for non-

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invasive measurement of blood flow in post-natal subjects. Cardiovascular anatomical MRI is an 
essential diagnostic tool in the evaluation of the heart post-natally. It is non-invasive, provides excellent 
soft tissue contrast and has the ability to perform multi-planar imaging in any orientation. PC MRI and 
anatomical MRI of the heart necessitate synchronization of image acquisition with the cardiac phase, 
which is most often facilitated by an electrocardiogram (ECG) signal.  
 
In the case of fetal cardiovascular complications such as CHD, evaluation of the fetal heart is important 
for guiding treatment of disease, timing of delivery, and planning appropriate care after birth. Detection 
of the fetal heart beat through ECG has been done by placing electrodes on the mother’s abdomen. 
Even after decades of developments in fetal ECG, detection of the fetal heart beat through ECG has 
been shown to be fundamentally unreliable due to the relatively small electric potentials generated 
from the fetal heart, interference from other potentials generated by the mother, and shielding from 
many layers of tissue [5]. A very low conductivity layer of tissue called the vernix caseosa which forms 
around the fetus between the 28th and 32nd weeks of gestation, makes detection of an fetal ECG signal 
particularly difficult [5]. Lack of an available ECG signal from the fetus necessitates the use of novel 
cardiac gating techniques for MRI. For this, we propose to investigate the use of an MRI-compatible 
Doppler ultrasound probe to produce a gating signal from the fetal heart. The Doppler ultrasound probe 
detects blood flow through the fetal heart, which can be used to trigger MRI data acquisition and 
produce dynamic images of the fetal heart. Our collaborators have successfully used this technique to 
produce a cardiac gating signal for MRI gating in non-pregnant adult humans [6], fetal humans [7], and 
fetal sheep [8].   
 
This study will be conducted in compliance with this research protocol, GCP guidelines and with the 
Hospital for Sick Children’s regulatory requirements.  
 
Significance 
Cardiac gated fetal MRI methods will enable accurate assessment of fetal cardiovascular function and 
development. The prospective gating provided by the Doppler ultrasound probe will allow direct 
translation of postnatal MRI techniques to the evaluation of pathologies like fetal heart disease and 
intrauterine growth restriction, to better guide treatments such as early delivery and to plan appropriate 
care after birth.  
 
Hypotheses/Research Questions 
Our proposal is geared toward method development and validation of MRI scanning techniques. We will 
compare dynamic cardiac images and blood flow patterns obtained using prospectively gated MRI with 
those obtained using conventional diagnostic ultrasound imaging. We will also compare MRI 
measurements made with the newly developed prospective gating method to un-gated and 
retrospectively gated MRI. 
 
Our primary objective is to assess the feasibility of using Doppler ultrasound gated MRI for advanced 
fetal monitoring, which would include understanding the relationship between maternal-placental-fetal 
cardiovascular physiologies in utero. To achieve the primary objective, the following foundational 
objectives need to be accomplished: 
 
(1) Incorporate fetal gating information from a novel Doppler ultrasound probe into our existing MRI 
pulse sequences and reconstruction software 

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(2) Validate Doppler ultrasound gated MRI by comparison to MRI images created without gating 
information from the Doppler ultrasound probe, in addition to measurements made with clinical 
ultrasound 
(3) Assess utility of prospective Doppler ultrasound gating for fetal MRI compared to un-gated and 
retrospectively gated fetal MRI 
Procedures 
Pregnant volunteers carrying a fetus affected by congenital heart disease who are scheduled for a 
clinical fetal ultrasound examination at the Fetal Echocardiography Clinic at SickKids will be invited to 
undergo an MRI, where MRI techniques incorporating Doppler ultrasound gating will be tested. 
Participants will be scanned with the Siemens PrismaFIT or Siemens Magnatom Skyra, both which are 3T 
MRIs at SickKids. We will enroll 20 pregnant volunteers (10 in the 2nd trimester and 10 in the 3rd), 
allowing for method development and testing at different gestational ages, providing more dramatic 
variation in anatomy and vessel size and more variation in the types and magnitude of fetal motion.  
During scanning, pregnant mothers will be asked to remain still for periods of time on the order of 5 
minutes as pulse sequences are run.  
 
The Doppler ultrasound fetal gating device, which will be placed on the patient’s abdomen by a 
registered MRI technician and held in place with a flexible elastic band, will be connected to the gating 
input of the MRI for either the entirety of, or a portion of the MRI examination. As is the case with all 
clinical ultrasound examinations, a water-based gel will be applied to the mother’s skin below where the 
gating device is placed. Foam padding will be placed around the transducer cable to shield from possible 
heating of the cable. The gating device will detect when each fetal cardiac cycle begins and trigger MRI 
acquisition. MRI examinations will be up to 60 minutes in length. The MRI examination will be scheduled 
on the same day that volunteers have their clinical ultrasound appointment, with both examinations 
occurring within the shortest time-period that can reasonably be achieved.  
 
Data Collection / Analysis 
Anatomic MR images of the fetal heart (be they single or multi-slice), phase-contrast MR images of 
blood flow in great fetal vessels, and T1 and T2 maps in great fetal vessels will be acquired using 
prospective gating information from the Doppler ultrasound probe. Similarly, anatomical images, phase 
contrast images, and T1 and T2 maps will be acquired without any gating input. From the ultrasound 
examination during the patient’s visit to the Fetal Echocardiography Clinic, we will retrieve anatomical 
images of the fetal heart in addition to flow waveforms acquired in the great fetal vessels.  
 
MR data acquired without the Doppler ultrasound gating signal will be reconstructed without any gating 
information, and will also be reconstructed using retrospective gating techniques that we have 
previously developed [9], [10]. Anatomic MR images will be compared quantitatively in terms of 
myocardial border sharpness, with the anticipated result that Doppler gated MR will show higher border 
sharpness than un-gated or retrospectively gated MR. Ejection fraction will be calculated from 
anatomical cardiac images. These estimates of ejection fraction will be compared to ejection fraction 
calculated from the ultrasound images, with the anticipated result that Doppler gated MR will agree 
better with ultrasound images than un-gated or retrospectively gated MR.  
 

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T1 and T2 maps will be compared in terms of the standard deviation of T1/T2 values in ROIs placed in 
the larger great fetal vessels, with the anticipated result that Doppler gated MR will provide a tighter 
distribution than un-gated or retrospectively gated MR. From the ungated, retrospectively gated, and 
Doppler ultrasound gated cardiac images, we will calculate ejection fraction.  
 
Flow waveforms in great fetal vessels derived from retrospectively gated and Doppler ultrasound gated 
phase contrast images will be compared to flow waveforms measured with clinical Doppler ultrasound 
during the patient’s visit to the Fetal Echocardiography Clinic (which we view as a gold standard). We 
anticipate that flow waveforms derived from Doppler ultrasound gated MR will prove to be more similar 
to the gold standard than flow waveforms derived from retrospectively gated MR.  
 
Once enrolled, participants will be assigned a study number and all data and images gathered from the 
study procedures will be de-identified so to be identifiable only by this number and not any personal 
health information. Results of this study will be published in conference presentations and proceedings, 
peer reviewed journals, and academic rounds.  
 
Inclusion and exclusion criteria 
Inclusion criteria: 
-pregnant adults (age 18 and up) with fetus affected by congenital heart disease 
-singleton pregnancy in their 2nd and 3rd trimesters 
-scheduled for a clinical fetal ultrasound examination at the Fetal Echocardiography Clinic at SickKids  
 
Exclusion criteria: 
Exclusion criteria that prevent the mother from having an MRI 
-claustrophobia 
-cardiac pacemaker 
-non-MRI compatible implants 
 
Other exclusion criteria 
-non-singleton pregnancy 
-obesity (BMI > 30)  
 
Possible harm to the patients: 
Fetal MRI has been used for more than 25 years and poses no risk to the fetus in the 2nd and 3rd 
trimesters of pregnancy [11]. MRI does not use ionizing radiation, which is known to be harmful to the 
fetus, and risks are primarily related to the rise in body temperature due to absorption of radio-
frequency energy. The UK National Radiological Protection Board suggests that MRI be restricted to the 
2nd and 3rd trimester because of theoretical concerns about teratogenesis with MRI in early pregnancy 
[12], however recent studies of incidental MRI use in 1st trimester pregnancies have demonstrated no 
increase in adverse outcomes in these cases when no MR contrast agent is used [13].  In fetal MRI, 
current data and research studies have failed to demonstrate any reproducible harmful effects on 
pregnant women and their fetuses at magnetic field strengths of 3T or less [14].  The International 
Commission on Non-Ionizaing Radiation Protection concludes that “adverse developmental effects [on 
the fetus] will be avoided with a margin of safety if the body temperature of pregnant women does not 
rise by more than 0.5 ˚C and the temperature of the fetus is less that 38 ˚C” [15].  
 

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MRI manufacturers have adapted the International Electrotechnical Commission (IEC) standard IEC 606-
1-2-33, which defines three levels of MRI RF exposure risk. The lowest risk level, normal mode, sets a 
maximum specific absorption rate (SAR) of 2 W/kg and a maximum temperature rise of 0.5 ˚C. Before 
any MR pulse sequence is run, an estimate of whole-body SAR and temperature rise is made, which 
accounts for the patient’s height, weight, ambient temperature and humidity, and details of the MR 
pulse sequence. When operating in normal mode, the scanner will simply not run a pulse sequence if 
the estimated SAR or temperature rise exceeds the thresholds defined by IEC normal mode.  It is known 
that the fetal temperature rests ~0.5 ˚C above the maternal body temperature (which is 37 ˚C) due to 
limited pathways for heat transfer [16]. Numerical simulations suggest that fetal temperature will not 
pass 38˚C when a mother is scanned in normal mode [16], giving assurance that we will operate within 
internationally recognized safety limits.  
 
Concerns related to the loud noises generated by the MR coils and their potential to cause acoustic 
damage to the fetus have been dispelled by several studies [11]. 
 
In addition to the ultrasound that volunteers will undergo to validate our MRI techniques, ultrasound is 
the enabling technology behind the Doppler ultrasound probe used for fetal cardiac gating. Doppler 
ultrasound detects blood velocity by transmitting acoustic waves into the patient and then detecting 
waves that reflect back from moving red blood cells. Ultrasounds are included in routine prenatal care 
around the world and no harmful effects have ever been detected. Theoretical concerns are related to 
tissue heating (as in MRI) in addition to ultrasonic gaseous cavitation [17]. The Doppler ultrasound probe 
will be built by our collaborators from the Department of Diagnostic and Interventional Radiology at the 
University Medical Centre in Hamburg, Germany where they have received ethics approval for use in 
non-pregnant adult human volunteers [6] and later, for fetal imaging in pregnant adult volunteers [7]. 
The transducer transmits acoustic energy at a maximum (pulse averaged) power of 1.5 mW/cm2, which 
is well below the limit of 20 mW/cm2 set by Health Canada for Doppler ultrasound based fetal heart rate 
monitors [18].  
 
This study will not proceed before we receive Health Canada approval to use this new medical device.  
 
It is known that use of ultrasonic gels carries a small risk of spreading bacterial infections [19]. Health 
Canada mandates that sterile gels be used in all procedures that pass a device through tissue (such as 
ultrasound guided tissue biopsy) or where the ultrasound transducer makes contact with a mucus 
membrane. Because we will only put the ultrasound gel on intact skin, there is minimal risk of spreading 
infection. The ultrasound transducer will be cleaned with an antibacterial disinfectant after each use, 
and Health Canada guide-lines regarding use of non-sterile ultrasound gels, as outlined in [20] will be 
followed.  
 
The device manufacturer reports that in rare circumstances, the cable that connects to the transducer 
can heat to up to 70 °C. They have insulated the cable with foam padding. With the insulation attached, 
the surface temperature of the cable will not exceed 43 °C. Since the cable can make contact with the 
participant’s skin, this may cause minor discomfort.  
 
Any adverse events (such as injury during MRI examination) will be reported to the SickKids Research 
Ethics Board. 
 
 
 
 

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Possible benefit to the patient: 
Fetal cardiac MRI provides a way of making pictures of the fetus, in addition to conventional ultrasound 
screening, and may result in visualization of previously undetected abnormalities. The probability of 
such benefits to the patients is very small because such abnormalities would likely have been detected 
by ultrasound during normal standard of care. In such a situation, Dr. Mike Seed, who is in the patient’s 
circle of care, will be informed of the findings and will take appropriate action.  
 
 
Possible benefit to society: 
Fetal cardiac MRI methods will enable more accurate assessment of fetal cardiovascular function and 
development. The imaging techniques provided by the methods we develop will allow for early 
evaluation of fetal heart and/or placental disease to better guide treatments such as early delivery and 
to plan appropriate care after birth. 
 
Data collection and storage: 
The source images from the study will be de-identified and stored on the secure hospital research PACS 
system with password-protected access. The de-identified data will be associated with a code, and the 
key-code will be stored in password-protected files on an internal hospital directory. The data will be 
destroyed after a period of 7 years. De-identified MRI and ultrasound data will be shared with our 
collaborator (Fabian Kording) at the University Medical Centre Hamburg-Eppendorf in Hamburg, 
Germany. Data will be transferred using the SickKids RIT-FTP service. Only the study team identified will 
have access to the patient data.  
 
Withdrawal from study participation: 
Participants can withdraw from the study at any point, for any reason, specified or unspecified, without 
penalty. No new data will be collected or linked to other data from that point on. Upon request any 
processed and unprocessed data can be destroyed. 
 
Research budget and funding:  
The main cost of this study is the cost of the MRI examinations, which are $500 per hour. Each 
participant will be reimbursed for travel and parking, costing up to $33.50. We will pay to make our 
publications open access, for which we will allocate $2000. The total cost of this project could reach 
$12,670. A total sum $30,000 is available through CIHR funding. 
 

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References 
[1] 
M. Y. Zhu, N. Milligan, S. Keating, R. Windrim, J. Keunen, V. Thakur, A. Ohman, S. Portnoy, J. G. Sled, E. Kelly, 
S. J. Yoo, L. Gross-Wortmann, E. Jaeggi, C. K. MacGowan, J. C. Kingdom, and M. Seed, “The hemodynamics 
of late-onset intrauterine growth restriction by MRI,” Am. J. Obstet. Gynecol., vol. 214, no. 3, p. 367.e1-
367.e17, Mar. 2016. 
[2] 
G. R. DeVore, “Assessing fetal cardiac ventricular function.,” Semin. Fetal Neonatal Med., vol. 10, no. 6, pp. 
515–41, Dec. 2005. 
[3] 
H. F. Sandmire and R. K. DeMott, “Electronic fetal heart rate monitoring: research guidelines for 
interpretation.,” Am. J. Obstet. Gynecol., vol. 179, no. 1, pp. 276–277, 1998. 
[4] 
Y. Li and X. Zhang, “Advanced MR Imaging Technologies in Fetuses,” Omi. J Radiol, vol. 1, no. (4), pp. e113-
119, 2012. 
[5] 
R. Sameni and G. D. Clifford, “A Review of Fetal ECG Signal Processing; Issues and Promising Directions.,” 
Open Pacing Electrophysiology Therapy J., vol. 3, pp. 4–20, 2010. 
[6] 
F. Kording, B. Schoennagel, G. Lund, F. Ueberle, C. Jung, G. Adam, and J. Yamamura, “Doppler ultrasound 
compared with electrocardiogram and pulse oximetry cardiac triggering: A pilot study,” Magn. Reson. Med., 
vol. 74, no. 5, pp. 1257–1265, Nov. 2015. 
[7] 
J. Yamamura, B. Schoennagel, M. Tavares, M. Kladeck, G. Adam, C. Ruprecht, and F. Kording, “Fetal cardiac 
MRI and Flow-measurement using Optimized Doppler-Ultrasound Sensor (DUS) gating,”  ISMRM Conference 
Record, 2016, p. abstract 0974. 
[8] 
F. Ueberle, E. Dettmann, C. Eden, J. Jayakumar, M. Jelinek, C. Much, B. Schönnagel, M. Tavares de Sousa, U. 
Wedegärtner, and J. Yamamura, “Cardiac MR: Imaging of the Foetal Heart Dynamics using Doppler 
Ultrasound Triggering.,” Biomed TEch, vol. 57, no. Suppl.1, pp. 1–4, 2012. 
[9] 
M. S. Jansz, M. Seed, J. F. P. Van Amerom, D. Wong, L. Grosse-Wortmann, S. J. Yoo, and C. K. MacGowan, 
“Metric optimized gating for fetal cardiac MRI,” Magn. Reson. Med., vol. 64, no. 5, pp. 1304–1314, 2010. 
[10] 
C. W. Roy, M. Seed, and C. K. Macgowan, “Accelerated MRI of the fetal heart using compressed sensing and 
metric optimized gating,” Magn. Reson. Med., vol. 0, pp. 1–11, 2016. 
[11] 
F. V. Coakley, O. A. Glenn, A. Qayyum, A. J. Barkovich, R. Goldstein, and R. A. Filly, “Fetal MRI: A Developing 
Technique for the Developing Patient,” Am. J. Roentgenol., vol. 182, no. 1, pp. 243–252, 2004. 
[12] 
National Radiological Protection Board, “Principles for the Protection of Patients and Volunteers during 
Clinical Magnetic Resonance Diagnostic Procedures,” Ann. N. Y. Acad. Sci., vol. 649, no. 1, pp. 372–375, 
1992. 
[13] 
J. G. Ray, M. J. Vermeulen, A. Bharatha, W. J. Montanera, and A. L. Park, “Association Between MRI 
Exposure During Pregnancy and Fetal and Childhood Outcomes,” JAMA, vol. 316, no. 9, p. 952, 2016. 
[14] 
S. Tocchio, B. Kline-Fath, E. Kanal, V. J. Schmithorst, and A. Panigrahy, “MRI evaluation and safety in the 
developing brain,” Seminars in Perinatology, vol. 39, no. 2., pp. 73–104, 2015. 

September 19, 2019 
 
Page 8 of 8 
  
[15] 
International Commission on Non-Ionizing Radiation Protection, “Statement on medical magnetic 
resonance (MR) procedures: protection of patients,” Health Phys., vol. 87, no. 2, p. 197, 2004. 
[16] 
J. W. Hand, Y. Li, and J. V Hajnal, “Numerical study of RF exposure and the resulting temperature rise in the 
foetus during a magnetic resonance procedure,” Phys Med Biol, vol. 55, pp. 913–930, 2010. 
[17] 
D. L. Miller, “Safety Assurance in Obstetrical Ultrasound,” Semin. Ultrasound, CT MRI, vol. 29, no. 2, pp. 
156–164, 2008. 
[18] 
Health Canada, “GUIDANCE FOR INDUSTRY - Device Licence Applications for Ultrasound Diagnostic Systems 
and 
Transducers.,” 
2006, 
url: 
http://www.hc-sc.gc.ca/dhp-mps/md-im/applic-demande/guide-
ld/ultrasound_ultrasons-eng.php 
[19] 
S. C. Oleszkowicz, P. Chittick, V. Russo, P. Keller, M. Sims, and J. Band, “Infections Associated with Use of 
Ultrasound Transmission Gel: Proposed Guidelines to Minimize Risk,” Infect. Control Hosp. Epidemiol., vol. 
33, no. 12, pp. 1235–1237, 2012. 
[20] 
Health Canada, “Notice to Hospitals: Important Safety Information on Ultrasound and Medical Gels.”, url: 
http://www.healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2004/14290a-
eng.php?_ga=1.243051650.1024799928.1416943151