All MRI scans were performed with informed consent from volunteers as part of a study approved by our institutional research ethics board.
NOTE: The methods described below have been used on a 3T MRI system. The acquisition is performed using a radial phase contrast MRI sequence. This sequence was prepared by modifying the readout trajectory (to achieve a stellate pattern) of the manufacturer&#39;s Cartesian phase contrast MRI. The sequence and sample protocols are available upon request throu...

<ol>
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S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fetal+movement:+development+and+time+course.">Fetal movement: development and time course.</a> Science. 169 (3940), 95-97 (1970).</li><li>Malamateniou, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motion-Compensation+Techniques+in+Neonatal+and+Fetal+MR+Imaging.">Motion-Compensation Techniques in Neonatal and Fetal MR Imaging.</a> American Journal of Neuroradiology. 34 (6), 1124-1136 (2013).</li><li>Rutherford, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MR+imaging+methods+for+assessing+fetal+brain+development.">MR imaging methods for assessing fetal brain development.</a> Developmental Neurobiology. 68 (6), 700-711 (2008).</li><li>Haris, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Self-gated+fetal+cardiac+MRI+with+tiny+golden+angle+iGRASP:+A+feasibility+study:+Self-Gated+Fetal+Cardiac+MRI+with+iGRASP.">Self-gated fetal cardiac MRI with tiny golden angle iGRASP: A feasibility study: Self-Gated Fetal Cardiac MRI with iGRASP.</a> Journal of Magnetic Resonance Imaging. 46 (1), 207-217 (2017).</li><li>Glenn, O. 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C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Self-gated+cardiac+cine+MRI.">Self-gated cardiac cine MRI.</a> Magnetic Resonance in Medicine. 51 (1), 93-102 (2004).</li><li>Knoll, F., Schwarzl, A., Diwoky, C., Sodickson, D. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=gpuNUFFT-An+open+source+GPU+library+for+3D+regridding+with+direct+Matlab+interface.">gpuNUFFT-An open source GPU library for 3D regridding with direct Matlab interface.</a> Proceedings of the 22nd Annual Meeting of ISMRM. , (2014).</li><li>Klein, S., Staring, M., Murphy, K., Viergever, M. A., Pluim, J. P. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=elastix:+a+toolbox+for+intensity-based+medical+image+registration.">elastix: a toolbox for intensity-based medical image registration.</a> IEEE Transactions on Medical Imaging. 29 (1), 196-205 (2010).</li><li>Walker, P. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Semiautomated+method+for+noise+reduction+and+background+phase+error+correction+in+MR+phase+velocity+data.">Semiautomated method for noise reduction and background phase error correction in MR phase velocity data.</a> Journal of Magnetic Resonance Imaging. 3 (3), 521-530 (1993).</li><li>Heiberg, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Design+and+validation+of+Segment+-+freely+available+software+for+cardiovascular+image+analysis.">Design and validation of Segment - freely available software for cardiovascular image analysis.</a> BMC Medical Imaging. 10 (1), 1 (2010).</li><li>Inder, T. E., Volpe, J. 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This method enables the non-invasive measurement of blood flow in human fetal great vessels and allows for retrospective motion correction and cardiac gating by making use of iterative reconstruction techniques. Fetal blood flow quantification has been performed with MRI in the past1,3,8,9. These studies had a prospective approach to mitigate motion corruption w...

Comprehensive assessment of the fetal circulation is necessary for monitoring fetal pathologies such as fetal growth restriction (FGR) and congenital heart disease (CHD)1,2,3. In utero, patient management and planning for postnatal care depend on the severity of the fetal pathology4,5,6,7. Feasibility of fetal blood flow quantification with MRI and its applications in assessing fetal pathologies have recently been demonstrated3,8,9. The imaging method, however, faces challenges, such as increased imaging times to achieve high spatiotemporal resolution, lack of cardiac synchronization methods, and unpredictable fetal motion10.
Fetal vasculature comprises small structures (~5 mm diameter for major blood vessels that comprise the descending aorta, ductus arteriosus, ascending aorta, main pulmonary artery, and superior vena cava11,12,13).To resolve these structures and to quantify flow, imaging at high spatial resolution is required. Moreover, the fetal heart rate is about twice that of an adult. A high temporal resolution is thus also required to resolve dynamic cardiac motion and blood flow across the fetal cardiac cycle. Conventional imaging at this high spatiotemporal resolution requires relatively long acquisition times. To address this issue, accelerated fetal MRI14,15,16&#160;has been introduced. Briefly, these acceleration techniques involve undersampling in the frequency domain during data acquisition and retrospective high-fidelity reconstruction using iterative techniques. One such approach is compressed sensing (CS) reconstruction, which allows reconstruction of images from heavily undersampled data when the reconstructed image is sparse in a known domain and undersampling artifacts are incoherent17.
Motion in fetal imaging presents a major challenge. Motion corruption can arise from maternal respiratory motion, maternal bulk motion or gross fetal movement. Maternal respiration leads to periodic translations of the fetus, whereas fetal movements are more complex. Fetal movements can be classified as localized or gross10,18. Localized movements involve motion of only segments of the body. They typically last for about 10-14 s and their frequency increases with gestation (~90 per hour at term)10. These movements generally cause small corruptions and do not affect the imaging area of interest. However, gross fetal movements can lead to severe image corruption with through plane motion components. These movements are whole body movements mediated by the spine and last for 60-90 s.
To avoid artifacts from fetal motion, steps are first taken to minimize maternal motions. Pregnant women are made more relaxed using supportive pillows on the scanner bed and dressed in comfortable gowns and may have their partners present beside the scanner to reduce claustrophobia19,20. To mitigate effects of maternal respiratory motion, studies have performed fetal MR exams under maternal breath-hold21,22,23. However, such acquisitions must be short (~15 s) given the reduced breath-hold tolerance of pregnant subjects. Recently, retrospective motion correction methods have been introduced for fetal MRI14,15,16. These methods track fetal motion using registration toolkits and correct for motion or discard uncorrectable portions of acquired data.
Finally, postnatal cardiac MR images are conventionally acquired using electrocardiogram (ECG) gating to synchronize data acquisition to the cardiac cycle. Without gating, cardiac motion and pulsatile flow from throughout the cardiac cycle are combined, producing artifacts. Unfortunately, the fetal ECG signal suffers from interference from the maternal ECG signal24&#160;and distortions from the magnetic field25. Hence, alternative non-invasive approaches to fetal cardiac gating have been proposed, including self-gating, metric optimized gating (MOG) and doppler ultrasound gating21,26,27,28.
As described in the following sections, our MRI approach to quantify fetal blood flow leverages a novel gating method, MOG, developed in our laboratory and combined with motion correction and iterative reconstruction of accelerated MRI acquisitions. The approach is based on a pipeline in a previously published study14&#160;and is composed of the following five stages: (1) fetal blood flow acquisition, (2) real-time reconstructions, (3) motion correction, (4) cardiac gating, and (5) gated reconstructions.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>elastix</td>
			<td>Image Sciences Institute, University Medical Center Utrecht</td>
			<td></td>
			<td>Image registration software</td>
		</tr>
		<tr>
			<td>Geforce GTX 960&#160;</td>
			<td>Nvidia&#160;</td>
			<td>04G-P4-3967-KR</td>
			<td></td>
		</tr>
		<tr>
			<td>gpuNUFFT</td>
			<td>CAI&#178;R</td>
			<td></td>
			<td>Non-uniform fast Fourier transform</td>
		</tr>
		<tr>
			<td>MAGNETOM Prisma</td>
			<td>Siemens</td>
			<td>10849583</td>
			<td></td>
		</tr>
		<tr>
			<td>MATLAB</td>
			<td>MathWorks</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Radial Phase Contrast MRI sequence</td>
			<td></td>
			<td></td>
			<td>Trajectory modification of manufacturer&#39;s Cartesian Phase Contrast sequence</td>
		</tr>
		<tr>
			<td>Segment</td>
			<td>Medvisio</td>
			<td></td>
			<td>Data analysis</td>
		</tr>
		<tr>
			<td>VENGEANCE</td>
			<td>Corsair</td>
			<td>LPX DDR4-2666&#160;</td>
			<td></td>
		</tr>
	</tbody>
</table>

human fetal blood flow quantification with magnetic resonance imaging and motion compensation

Magnetic resonance imaging (MRI) is an important tool for the clinical assessment of cardiovascular morphology and heart function. It is also the recognized standard-of-care for blood flow quantification based on phase contrast MRI. While such measurement of blood flow has been possible in adults for decades, methods to extend this capability to fetal blood flow have only recently been developed.
Fetal blood flow quantification in major vessels is important for monitoring fetal pathologies such as congenital heart disease (CHD) and fetal growth restriction (FGR). CHD causes alterations in the cardiac structure and vasculature that change the course of blood in the fetus. In FGR, the path of blood flow is altered through the dilation of shunts such that the oxygenated blood supply to the brain is increased. Blood flow quantification enables assessment of the severity of the fetal pathology, which in turn allows for suitable&#160;in utero&#160;patient management and planning for postnatal care.
The primary challenges of applying phase contrast MRI to the human fetus include small blood vessel size, high fetal heart rate, potential MRI data corruption due to maternal respiration, unpredictable fetal movements, and lack of conventional cardiac gating methods to synchronize data acquisition. Here, we describe recent technical developments from our lab that have enabled the quantification of fetal blood flow using phase contrast MRI, including advances in accelerated imaging, motion compensation, and cardiac gating.

In general, phase MRI examinations of flow target six major fetal vessels: the descending aorta, ascending aorta, main pulmonary artery, ductus arteriosus, superior vena cava, and umbilical vein. These vessels are of interest to the clinician as they are often implicated in CHD and FGR, influencing the distribution of blood throughout the fetus9. A typical scan duration with the radial phase contrast MRI is 17 s per vessel such that the scans are short while also allowing time for enough data acqu...

Watch this Scientific Journal Video about Human Fetal Blood Flow Quantification with Magnetic Resonance Imaging and Motion Compensation at JoVE.com

Human Fetal Blood Flow Quantification with Magnetic Resonance Imaging and Motion Compensation

Here we present a protocol for measuring fetal blood flow rapidly with MRI and retrospectively performing motion correction and cardiac gating.

Magnetic resonance imaging (MRI) is an important tool for the clinical assessment of cardiovascular morphology and heart function. It is also the ...

Fetal MRI faces several challenges. This protocol addresses the issues of fetal motion, high, spatial and temporal resolution requirements, and lack of external gating methods. This technique makes use of accelerated imaging through compressed sensing which reduces the imaging time, retrospectively corrects for fetal motion, and allows extraction of the fetal heart rate using metric optimized gating.Currently, this technique is only for research, however it has the potential for the monitoring and therapy guidance for fetal pathologies, such as congenital heart disease and intrauterine growth restriction. After assisting the mother in an appropriate comfortable position on the MRI table, set the instrument to run a localizer exam to locate the fetal body at a 0.9 by 0.9 by 10 cubic centimeter resolution, an echo time of five milliseconds, a repetition time of 15 milliseconds, a field of view of 450 by 450 square millimeter and six slices. Set the parameters for running a refined localizer exam to locate the fetal vasculature with the slice group centered on the fetal heart at 1.1 by 1.1 by six cubic millimeter resolution, echo time of 2.69 milliseconds, repetition time of 1335.4 milliseconds, a field of view of 350 by 350 square millimeters, 10 slices and an axial to fetus orientation.Then repeat the refined localizers with sagittal and coronal orientations to obtain a clearer view of the fetal vessels. To measure the fetal blood flow, after locating the fetal vessels identify the vessels of interest. For example, the descending aorta is a long straight vessel near the spine in the sagittal plains, the ascending aorta and main pulmonary arteries can be identified as vessels leaving the left and right ventricles respectively.The ductus arteriosus can be tracked as a downstream segment of the main pulmonary artery proximal to the descending aorta. The superior vena cava can be identified from axial plains near the base of the fetal heart as the vessel adjacent to the ascending aorta. Prescribe a slice perpendicular to the axis of the fetal vessel of interest and rotate and move the slice guideline on the MRI console such that the slice intersects the target vessel perpendicularly.Set the scan parameters to a radial phase contrast MRI acquisition, a 1.3 by 1.3 by five cubic millimeter resolution, echo time of 3.25 milliseconds, resolution time of 5.75 milliseconds, field of view of 240 by 240 square millimeters, one slice, 100 to 150 centimeter per second velocity and coating according to the vessel of interest, through the plane, radio views velocity and coating direction, and 1500 per end code free breathing. After running the scan, verify the prescription based on the initial time averaged reconstruction performed and displayed on the MRI console. Repeat for each target blood vessel and if the target vessel is absent or identifiable.After reconstructing fetal flow CINEs, load the reconstructed data files into an appropriate flow analysis software program, and draw a region of interest encompassing the lumen of the blood vessel of interest in the anatomical and velocity sensitive images. Propagate the region of interest to all the cardiac phases and correct for changes in the vessel's diameter. Then record the flow measurements within each region of interest.In this representative analysis, the extracted motion parameters for fetus one and fetus two depict the motion of the descending aorta over the duration of the scan. Here, the shared mutual information of each real time frame with all of the other co registered frames for fetus one and fetus two can be observed. The second real time reconstructions used to derive the cardiac gating information took 10 minutes per slice, and the fetal heartbeat intervals were derived by metric optimized gating using a multi parameter model as demonstrated.Final CINE reconstructions. Using the retrospectively motion corrected and gated data took three minutes per slice, and allowed the generation of anatomical and velocity reconstructions for the fetuses, at peak systole. Reconstructions with motion correction show vessels with sharper walls.Without motion correction, the descending aorta is blurrier and less conspicuous. The measured flow curves from each fetus revealed higher peak and mean flows in the reconstructions without motion correction than those with motion correction. The technique is being used to study the blood distribution in fetal pathologies.An extension of this method has allowed multi-dimensional fetal flow visualization and measurement.

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JoVE Journal

Medicine

1.8K visualizações.  University of Toronto. A ressonância magnética fetal enfrenta vários desafios. Este protocolo aborda as questões de movimento fetal, requisitos de resolução alta, espacial e temporal e falta de métodos de bloqueio externo. Esta técnica faz uso de imagem acelerada através de sensoriamento comprimido que reduz o tempo de imagem, corrige retrospectivamente o movimento fetal e permite a extração da frequência cardíaca fetal usando o gating otimizado por métricas.Atualmente, essa técnica é apenas ...