Name: human fetal blood flow quantification with magnetic resonance imaging and motion compensation
Uploaded: 2021-01-07T13:00:00
Description: Watch this Scientific Journal Video about Human Fetal Blood Flow Quantification with Magnetic Resonance Imaging and Motion Compensation at JoVE.com

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>
	<li>Zhu, M. Y., 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=The+hemodynamics+of+late-onset+intrauterine+growth+restriction+by+MRI.">The hemodynamics of late-onset intrauterine growth restriction by MRI.</a> American Journal of Obstetrics and Gynecology. 214 (3), 1-17 (2016).</li><li>Zhu, M. Y., Jaeggi, E., Roy, C. W., Macgowan, C. K., Seed, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reduced+combined+ventricular+output+and+increased+oxygen+extraction+fraction+in+a+fetus+with+complete+heart+block+demonstrated+by+MRI.">Reduced combined ventricular output and increased oxygen extraction fraction in a fetus with complete heart block demonstrated by MRI.</a> HeartRhythm Case Reports. 2 (2), 164-168 (2016).</li><li>Sun, L., 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=Reduced+Fetal+Cerebral+Oxygen+Consumption+is+Associated+With+Smaller+Brain+Size+in+Fetuses+With+Congenital+Heart+Disease.">Reduced Fetal Cerebral Oxygen Consumption is Associated With Smaller Brain Size in Fetuses With Congenital Heart Disease.</a> Circulation. 131 (15), 1313-1323 (2015).</li><li>Freud, L. R., 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=Fetal+aortic+valvuloplasty+for+evolving+hypoplastic+left+heart+syndrome:+postnatal+outcomes+of+the+first+100+patients.">Fetal aortic valvuloplasty for evolving hypoplastic left heart syndrome: postnatal outcomes of the first 100 patients.</a> Circulation. 130 (8), 638-645 (2014).</li><li>Peleg, D., Kennedy, C. M., Hunter, S. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intrauterine+growth+restriction:+identification+and+management.">Intrauterine growth restriction: identification and management.</a> American Family Physician. 58 (2), 453-467 (1998).</li><li>Krishna, U., Bhalerao, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Placental+Insufficiency+and+Fetal+Growth+Restriction.">Placental Insufficiency and Fetal Growth Restriction.</a> Journal of Obstetrics and Gynaecology of India. 61 (5), 505-511 (2011).</li><li>Seravalli, V., Miller, J. L., Block-Abraham, D., Baschat, A. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ductus+venosus+Doppler+in+the+assessment+of+fetal+cardiovascular+health:+an+updated+practical+approach.">Ductus venosus Doppler in the assessment of fetal cardiovascular health: an updated practical approach.</a> Acta Obstetricia et Gynecologica Scandinavica. 95 (6), 635-644 (2016).</li><li>Seed, 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=Feasibility+of+quantification+of+the+distribution+of+blood+flow+in+the+normal+human+fetal+circulation+using+CMR:+a+cross-sectional+study.">Feasibility of quantification of the distribution of blood flow in the normal human fetal circulation using CMR: a cross-sectional study.</a> Journal of Cardiovascular Magnetic Resonance. 14 (1), 79 (2012).</li><li>Prsa, 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=Reference+ranges+of+blood+flow+in+the+major+vessels+of+the+normal+human+fetal+circulation+at+term+by+phase-contrast+magnetic+resonance+imaging.">Reference ranges of blood flow in the major vessels of the normal human fetal circulation at term by phase-contrast magnetic resonance imaging.</a> Circulation. Cardiovascular Imaging. 7 (4), 663-670 (2014).</li><li>Piontelli, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Development of Normal Fetal Movements: The Last 15 Weeks of Gestation. , (2015).</li><li>Cartier, 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=The+normal+diameter+of+the+fetal+aorta+and+pulmonary+artery:+echocardiographic+evaluation+in+utero.">The normal diameter of the fetal aorta and pulmonary artery: echocardiographic evaluation in utero.</a> American Journal of Roentgenology. 149 (5), 1003-1007 (1987).</li><li>Ruano, R., de F&#225;tima Yukie Maeda, M., Niigaki, J. I., Zugaib, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pulmonary+artery+diameters+in+healthy+fetuses+from+19+to+40+weeks'+gestation.">Pulmonary artery diameters in healthy fetuses from 19 to 40 weeks' gestation.</a> Journal of Ultrasound in Medicine. 26 (3), 309-316 (2007).</li><li>Nowak, D., Koz&#322;owska, H., &#379;urada, A., Gielecki, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diameter+of+the+ductus+arteriosus+as+a+predictor+of+patent+ductus+arteriosus+(PDA).">Diameter of the ductus arteriosus as a predictor of patent ductus arteriosus (PDA).</a> Central European Journal of Medicine. 6 (4), 418-424 (2011).</li><li>Goolaub, D. S., 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=Multidimensional+fetal+flow+imaging+with+cardiovascular+magnetic+resonance:+a+feasibility+study.">Multidimensional fetal flow imaging with cardiovascular magnetic resonance: a feasibility study.</a> Journal of Cardiovascular Magnetic Resonance. 20 (1), 77 (2018).</li><li>Roy, C. W., Seed, M., Kingdom, J. C., Macgowan, C. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motion+compensated+cine+CMR+of+the+fetal+heart+using+radial+undersampling+and+compressed+sensing.">Motion compensated cine CMR of the fetal heart using radial undersampling and compressed sensing.</a> Journal of Cardiovascular Magnetic Resonance. 19 (1), 29 (2017).</li><li>van Amerom, J. F. P., 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=Fetal+cardiac+cine+imaging+using+highly+accelerated+dynamic+MRI+with+retrospective+motion+correction+and+outlier+rejection.">Fetal cardiac cine imaging using highly accelerated dynamic MRI with retrospective motion correction and outlier rejection.</a> Magnetic Resonance in Medicine. 79 (1), 327-338 (2018).</li><li>Lustig, M., Donoho, D., Pauly, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sparse+MRI:+The+application+of+compressed+sensing+for+rapid+MR+imaging.">Sparse MRI: The application of compressed sensing for rapid MR imaging.</a> Magnetic Resonance in Medicine. 58 (6), 1182-1195 (2007).</li><li>Edwards, D. D., Edwards, J. 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. A. <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+of+the+fetal+brain.">MR imaging of the fetal brain.</a> Pediatric Radiology. 40 (1), 68-81 (2010).</li><li>Rodr&#237;guez-Soto, A. 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=MRI+Quantification+of+Human+Fetal+O2+Delivery+Rate+in+the+Second+and+Third+Trimesters+of+Pregnancy.">MRI Quantification of Human Fetal O2 Delivery Rate in the Second and Third Trimesters of Pregnancy.</a> Magnetic Resonance in Medicine. 80 (3), 1148-1157 (2018).</li><li>Sameni, R., Clifford, G. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Review+of+Fetal+ECG+Signal+Processing;+Issues+and+Promising+Directions.">A Review of Fetal ECG Signal Processing; Issues and Promising Directions.</a> The Open Pacing, Electrophysiology &amp; Therapy Journal. 3, 4-20 (2010).</li><li>Millis, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Advances+in+Electrocardiograms:+Methods+and+Analysis.">Advances in Electrocardiograms: Methods and Analysis.</a> BoD - Books on Demand. , (2012).</li><li>Jansz, M. S., 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=Metric+optimized+gating+for+fetal+cardiac+MRI.">Metric optimized gating for fetal cardiac MRI.</a> Magnetic Resonance in Medicine. 64 (5), 1304-1314 (2010).</li><li>Yamamura, J., 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=Cardiac+MRI+of+the+fetal+heart+using+a+novel+triggering+method:+initial+results+in+an+animal+model.">Cardiac MRI of the fetal heart using a novel triggering method: initial results in an animal model.</a> Journal of Magnetic Resonance Imaging: JMRI. 35 (5), 1071-1076 (2012).</li><li>Larson, A. 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. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chapter+17+-+Intrauterine,+Intrapartum+Assessments+in+the+Term+Infant.">Chapter 17 - Intrauterine, Intrapartum Assessments in the Term Infant.</a> Volpe's Neurology of the Newborn (Sixth Edition). , 458-483 (2018).</li><li>Pelc, N. J., Herfkens, R. J., Shimakawa, A., Enzmann, D. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Phase+contrast+cine+magnetic+resonance+imaging.">Phase contrast cine magnetic resonance imaging.</a> Magnetic Resonance Quarterly. 7 (4), 229-254 (1991).</li><li>Steeden, J. A., Atkinson, D., Hansen, M. S., Taylor, A. M., Muthurangu, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rapid+flow+assessment+of+congenital+heart+disease+with+high-spatiotemporal-resolution+gated+spiral+phase-contrast+MR+imaging.">Rapid flow assessment of congenital heart disease with high-spatiotemporal-resolution gated spiral phase-contrast MR imaging.</a> Radiology. 260 (1), 79-87 (2011).</li><li>Kowalik, G. T., Knight, D., Steeden, J. A., Muthurangu, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Perturbed+spiral+real-time+phase-contrast+MR+with+compressive+sensing+reconstruction+for+assessment+of+flow+in+children.">Perturbed spiral real-time phase-contrast MR with compressive sensing reconstruction for assessment of flow in children.</a> Magnetic Resonance in Medicine. 83 (6), 2077-2091 (2020).</li></ol>

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.

human-fetal-blood-flow-quantification-with-magnetic-resonance-imaging

Research

JoVE Journal

Medicine

Magnetic Resonance Derived Myocardial Strain Assessment Using Feature Tracking

Purpose: An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that strain is a more sensitive and earlier marker for contractile dysfunction than the frequently used parameter EF. Current technologies for CMR are time consuming and difficult to implement in clinical practice. Feature tracking is a technology that can lead to more automization and robustness of quantitative analysis of medical images with less time consumption than comparable methods.
Methods: An automatic or manual input in a single phase serves as an initialization from which the system starts to track the displacement of individual patterns representing anatomical structures over time. The specialty of this method is that the images do not need to be manipulated in any way beforehand like e.g. tagging of CMR images.
Results: The method is very well suited for tracking muscular tissue and with this allowing quantitative elaboration of myocardium and also blood flow.
Conclusions: This new method offers a robust and time saving procedure to quantify myocardial tissue and blood with displacement, velocity and deformation parameters on regular sequences of CMR imaging. It therefore can be implemented in clinical practice.

An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that strain is a more sensitive and earlier marker for contractile dysfunction than the frequently used parameter EF.

Purpose: An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that ...

Magnetic Resonance Imaging Quantification of Pulmonary Perfusion using Calibrated Arterial Spin Labeling

This demonstrates a MR imaging method to measure the spatial distribution of pulmonary blood flow in healthy subjects 
during normoxia (inspired O2, fraction (FIO2) = 0.21) hypoxia (FIO2 = 0.125), and hyperoxia 
(FIO2 = 1.00). In addition, the physiological responses of the subject are monitored in the MR scan environment. MR images 
were obtained on a 1.5 T GE MRI scanner during a breath hold from a sagittal slice in the right lung at functional residual capacity. An arterial 
spin labeling sequence (ASL-FAIRER) was used to measure the spatial distribution of pulmonary blood flow 1,2 and a multi-echo fast 
gradient echo (mGRE) sequence 3 was used to quantify the regional proton (i.e. H2O) density, allowing the quantification 
of density-normalized perfusion for each voxel (milliliters blood per minute per gram lung tissue). 
With a pneumatic switching valve and facemask equipped with a 2-way non-rebreathing valve, different oxygen concentrations 
were introduced to the subject in the MR scanner through the inspired gas tubing. A metabolic cart collected expiratory gas via expiratory tubing. Mixed expiratory O2 and CO2 concentrations, oxygen consumption, carbon dioxide production, respiratory exchange ratio, 
respiratory frequency and tidal volume were measured. Heart rate and oxygen saturation were monitored using pulse-oximetry. 
Data obtained from a normal subject showed that, as expected, heart rate was higher in hypoxia (60 bpm) than during normoxia (51) or hyperoxia (50) and the arterial oxygen saturation (SpO2) was reduced during hypoxia to 86%. Mean ventilation was 8.31 L/min BTPS during hypoxia, 7.04 L/min during normoxia, and 6.64 L/min during hyperoxia. Tidal volume was 0.76 L during hypoxia, 0.69 L during normoxia, and 0.67 L during hyperoxia. 
Representative quantified ASL data showed that the mean density normalized perfusion was 8.86 ml/min/g during hypoxia, 8.26 ml/min/g during normoxia and 8.46 ml/min/g during hyperoxia, respectively. In this subject, the relative dispersion4, an index of global heterogeneity, was increased in hypoxia (1.07 during hypoxia, 0.85 during normoxia, and 0.87 during hyperoxia) while the fractal dimension (Ds), another index of heterogeneity reflecting vascular branching structure, was unchanged (1.24 during hypoxia, 1.26 during normoxia, and 1.26 during hyperoxia). 
Overview. This protocol will demonstrate the acquisition of data to measure the distribution of pulmonary perfusion noninvasively under conditions of normoxia, hypoxia, and hyperoxia using a magnetic resonance imaging technique known as arterial spin labeling (ASL). 
Rationale: Measurement of pulmonary blood flow and lung proton density using MR technique offers high spatial resolution images which can be quantified and the ability to perform repeated measurements under several different physiological conditions. In human studies, PET, SPECT, and CT are commonly used as the alternative techniques. However, these techniques involve exposure to ionizing radiation, and thus are not suitable for repeated measurements in human subjects.

A MR imaging method to study the distribution of pulmonary blood flow under a variety of physiological conditions, in this case exposure to three different inspired oxygen concentrations: hypoxia, normoxia, and hyperoxia, is described. This technique utilizes human pulmonary physiology research techniques in an MR scanning environment.

This demonstrates a MR imaging method to measure the spatial distribution of pulmonary blood flow in healthy subjects 
during normoxia (inspired O2, ...

Tracking the Mammary Architectural Features and Detecting Breast Cancer with Magnetic Resonance Diffusion Tensor Imaging

Breast cancer is the most common cause of cancer among women worldwide. Early detection of breast cancer has a critical role in improving the quality of life and survival of breast cancer patients. In this paper a new approach for the detection of breast cancer is described, based on tracking the mammary architectural elements using diffusion tensor imaging (DTI). 
The paper focuses on the scanning protocols and image processing algorithms and software that were designed to fit the diffusion properties of the mammary fibroglandular tissue and its changes during malignant transformation. The final output yields pixel by pixel vector maps that track the architecture of the entire mammary ductal glandular trees and parametric maps of the diffusion tensor coefficients and anisotropy indices. 
The efficiency of the method to detect breast cancer was tested by scanning women volunteers including 68 patients with breast cancer confirmed by histopathology findings. Regions with cancer cells exhibited a marked reduction in the diffusion coefficients and in the maximal anisotropy index as compared to the normal breast tissue, providing an intrinsic contrast for delineating the boundaries of malignant growth. Overall, the sensitivity of the DTI parameters to detect breast cancer was found to be high, particularly in dense breasts, and comparable to the current standard breast MRI method that requires injection of a contrast agent. Thus, this method offers a completely non-invasive, safe and sensitive tool for breast cancer detection.

We describe how to obtain parametric and vector maps of the diffusion tensor of the breast using magnetic resonance imaging. The protocol and final output following imaging processing are tailored for tracking breast architectural features and detecting breast malignancy.

Breast cancer is the most common cause of cancer among women worldwide. Early detection of breast cancer has a critical role in improving the quality of ...

Quantitative Magnetic Resonance Imaging of Skeletal Muscle Disease

Quantitative magnetic resonance imaging (qMRI) describes the development and use of MRI to quantify physical, chemical, and/or biological properties of living systems. Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multi-faceted pathology. The goal of this protocol is to characterize this pathology using qMRI methods. The MRI acquisition protocol begins with localizer images (used to locate the position of the body and tissue of interest within the MRI system), quality control measurements of relevant magnetic field distributions, and structural imaging for general anatomical characterization. The qMRI portion of the protocol includes measurements of the longitudinal and transverse relaxation time constants (T1 and T2, respectively). Also acquired are diffusion-tensor MRI data, in which water diffusivity is measured and used to infer pathological processes such as edema. Quantitative magnetization transfer imaging is used to characterize the relative tissue content of macromolecular and free water protons. Lastly, fat-water MRI methods are used to characterize fibro-adipose tissue replacement of muscle. In addition to describing the data acquisition and analysis procedures, this paper also discusses the potential problems associated with these methods, the analysis and interpretation of the data, MRI safety, and strategies for artifact reduction and protocol optimization.

Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multi-faceted pathology. The goal of this protocol is to characterize this pathology using non-invasive magnetic resonance imaging methods.

Quantitative magnetic resonance imaging (qMRI) describes the development and use of MRI to quantify physical, chemical, and/or biological properties of ...

Simultaneous PET/MRI Imaging During Mouse Cerebral Hypoxia-ischemia

Dynamic changes in tissue water diffusion and glucose metabolism occur during and after hypoxia in cerebral hypoxia-ischemia reflecting a bioenergetics disturbance in affected cells. Diffusion weighted magnetic resonance imaging (MRI) identifies regions that are damaged, potentially irreversibly, by hypoxia-ischemia. Alterations in glucose utilization in the affected tissue may be detectable by positron emission tomography (PET) imaging of 2-deoxy-2-(18F)fluoro-&#7429;-glucose ([18F]FDG) uptake. Due to the rapid and variable nature of injury in this animal model, acquisition of both modes of data must be performed simultaneously in order to meaningfully correlate PET and MRI data. In addition, inter-animal variability in the hypoxic-ischemic injury due to vascular differences limits the ability to analyze multi-modal data and observe changes to a group-wise approach if data is not acquired simultaneously in individual subjects. The method presented here allows one to acquire both diffusion-weighted MRI and [18F]FDG uptake data in the same animal before, during, and after the hypoxic challenge in order to interrogate immediate physiological changes.

The method presented here uses simultaneous positron emission tomography and magnetic resonance imaging. In the cerebral hypoxia-ischemia model, dynamic changes in diffusion and glucose metabolism occur during and after injury. The evolving and irreproducible damage in this model necessitates simultaneous acquisition if meaningful multi-modal imaging data are to be acquired.

Dynamic changes in tissue water diffusion and glucose metabolism occur during and after hypoxia in cerebral hypoxia-ischemia reflecting a bioenergetics ...

Cardiac Magnetic Resonance Imaging at 7 Tesla

CMR at an ultra-high field (magnetic field strength B0&#160;&#8805; 7 Tesla) benefits from the signal-to-noise ratio (SNR) advantage inherent at higher magnetic field strengths and potentially provides improved signal contrast and spatial resolution. While promising results have been achieved, ultra-high field CMR is challenging due to energy deposition constraints and physical phenomena such as transmission field non-uniformities and magnetic field inhomogeneities. In addition, the magneto-hydrodynamic effect renders the synchronization of the data acquisition with the cardiac motion difficult. The challenges are currently addressed by explorations into novel magnetic resonance technology. If all impediments can be overcome, ultra-high field CMR may generate new opportunities for functional CMR, myocardial tissue characterization, microstructure imaging or metabolic imaging. Recognizing this potential, we show that multi-channel radio frequency (RF) coil technology tailored for CMR at 7 Tesla together with higher order B0 shimming and a backup signal for cardiac triggering facilitates high fidelity functional CMR. With the proposed setup, cardiac chamber quantification can be accomplished in examination times similar to those achieved at lower field strengths. To share this experience and to support the dissemination of this expertise, this work describes our setup and protocol tailored for functional CMR at 7 Tesla.

The sensitivity gain inherent to ultrahigh field magnetic resonance holds promise for high spatial resolution imaging of the heart. Here, we describe a protocol customized for functional cardiovascular magnetic resonance (CMR) at 7 Tesla using an advanced multi-channel radio-frequency coil, magnetic field shimming and a triggering concept.

CMR at an ultra-high field (magnetic field strength B0&#160;&#8805; 7 Tesla) benefits from the signal-to-noise ratio (SNR) advantage inherent at higher ...

Phase Contrast Magnetic Resonance Imaging in the Rat Common Carotid Artery

Phase contrast magnetic resonance imaging (PC-MRI) is a noninvasive approach that can quantify flow-related parameters such as blood flow. Previous studies have shown that abnormal blood flow may be associated with systemic vascular risk. Thus, PC-MRI can facilitate the translation of data obtained from animal models of cardiovascular diseases to pertinent clinical investigations. In this report, we describe the procedure for measuring blood flow in the common carotid artery (CCA) of rats using cine-gated PC-MRI and discuss relevant analysis methods. This procedure can be performed in a live, anesthetized animal and does not require euthanasia after the procedure. The proposed scanning parameters yield repeatable measurements for blood flow, indicating excellent reproducibility of the results. The PC-MRI procedure described in this article can be used for pharmacological testing, pathophysiological assessment, and cerebral hemodynamics evaluation.

The overall goal of this procedure is to measure the blood flow in the rat common carotid artery by using noninvasive phase contrast magnetic resonance imaging.

Phase contrast magnetic resonance imaging (PC-MRI) is a noninvasive approach that can quantify flow-related parameters such as blood flow. Previous ...

Quantification of Levator Ani Hiatus Enlargement by Magnetic Resonance Imaging in Males and Females with Pelvic Organ Prolapse

Here we present a protocol to examine the levator ani hiatus in males and females with pelvic organ prolapse, during the Valsalva maneuver and while evacuating acoustic gel, using a horizontally oriented 1.5 T magnetic resonance (MR) scanner. On midsagittal images, the vertical distance of pelvic organs is measured in millimeters relative to the hymen plane (female) and to the lower border of the symphysis pubis (male), preceded by - (above) or + ( below) signs. On axial images, the levator ani area is calculated in square centimeters with a free-hand tracing method from three key images, passing through the midsymphysis (level I), tangential to the lower border of the symphysis (level II), and at the maximal anterior rectal wall bulging (level III). Areas at rest and strained are compared to find evidence of a percentage of increase. The purpose is to provide objective evidence of the maximal extent of pelvic organs descent and hiatus enlargement without the interference of foreign objects or the examiner&#39;s proximity, so as to overcome the limitations of pelvic examination and transperineal sonography (i.e., subjectivity and sex-related limitations [female only]).

Here we present a protocol to standardize the measurement of the levator ani hiatus size&#160;by magnetic resonance imaging. The purpose is to extract biomechanical inferences from image analysis by comparing resting and straining values in patients of both sexes with pelvic prolapse, using consistent anatomical bony landmarks.

Here we present a protocol to examine the levator ani hiatus in males and females with pelvic organ prolapse, during the Valsalva maneuver and while ...

Quantitative Mapping of Specific Ventilation in the Human Lung using Proton Magnetic Resonance Imaging and Oxygen as a Contrast Agent

Specific ventilation imaging (SVI) is a functional magnetic resonance imaging technique capable of quantifying specific ventilation &#8213; the ratio of the fresh gas entering a lung region divided by the region&#8217;s end-expiratory volume &#8213; in the human lung, using only inhaled oxygen as a contrast agent. Regional quantification of specific ventilation has the potential to help identify areas of pathologic lung function. Oxygen in solution in tissue shortens the tissue&#8217;s longitudinal relaxation time (T1), and thus a change in tissue oxygenation can be detected as a change in T1-weighted signal with an inversion recovery acquired image. Following an abrupt change between two concentrations of inspired oxygen, the rate at which lung tissue within a voxel equilibrates to a new steady-state reflects the rate at which resident gas is being replaced by inhaled gas. This rate is determined by specific ventilation. To elicit this sudden change in oxygenation, subjects alternately breathe 20-breath blocks of air (21% oxygen) and 100% oxygen while in the MRI scanner. A stepwise change in inspired oxygen fraction is achieved through use of a custom three-dimensional (3D)-printed flow bypass system with a manual switch during a short end-expiratory breath hold. To detect the corresponding change in T1, a global inversion pulse followed by a single shot fast spin echo sequence was used to acquire two-dimensional T1-weighted images in a 1.5&#160;T MRI scanner, using an eight-element torso coil. Both single slice and multi-slice imaging are possible, with slightly different imaging parameters. Quantification of specific ventilation is achieved by correlating the time-course of signal intensity for each lung voxel with a library of simulated responses to the air/oxygen stimulus. SVI estimations of specific ventilation heterogeneity have been validated against multiple breath washout and proved to accurately determine the heterogeneity of the specific ventilation distribution.

Specific ventilation imaging is a functional magnetic resonance imaging technique that allows for quantification of regional specific ventilation in the human lung, using inhaled oxygen as a contrast agent. Here, we present a protocol to collect and analyze specific ventilation imaging data.

Specific ventilation imaging (SVI) is a functional magnetic resonance imaging technique capable of quantifying specific ventilation &#8213; the ratio of ...

Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla

The overall goal of this article is to demonstrate a state-of-the-art ultrahigh field (UHF) magnetic resonance (MR) protocol of the brain at 7.0 Tesla in multiple sclerosis (MS) patients. MS is a chronic inflammatory, demyelinating, neurodegenerative disease that is characterized by white and gray matter lesions. Detection of spatially and temporally disseminated T2-hyperintense lesions by the use of MRI at 1.5 T and 3 T represents a crucial diagnostic tool in clinical practice to establish accurate diagnosis of MS based on the current version of the 2017 McDonald criteria. However, the differentiation of MS lesions from brain white matter lesions of other origins can sometimes be challenging due to their resembling morphology at lower magnetic field strengths (typically 3 T). Ultrahigh field MR (UHF-MR) benefits from increased signal-to-noise ratio and enhanced spatial resolution, both key to superior imaging for more accurate and definitive diagnoses of subtle lesions. Hence, MRI at 7.0 T has shown encouraging results to overcome the challenges of MS differential diagnosis by providing MS-specific neuroimaging markers (e.g., central vein sign, hypointense rim structures and differentiation of MS grey matter lesions). These markers and others can be identified by other MR contrasts other than T1 and T2 (T2*, phase, diffusion) and substantially improve the differentiation of MS lesions from those occurring in other neuroinflammatory conditions such as neuromyelitis optica and Susac syndrome. In this article, we describe our current technical approach to study cerebral white and grey matter lesions in MS patients at 7.0 T using different MR acquisition methods. The up-to-date protocol includes the preparation of the MR setup including the radio-frequency coils customized for UHF-MR, standardized screening, safety and interview procedures with MS patients, patient positioning in the MR scanner and acquisition of dedicated brain scans tailored for examining MS.

Here, we present a protocol to acquire magnetic resonance (MR) images of multiple sclerosis (MS) patient brains at 7.0 Tesla. The protocol includes preparation of the setup including the radio-frequency coils, standardized interview procedures with MS patients, subject positioning in the MR scanner and MR data acquisition.

The overall goal of this article is to demonstrate a state-of-the-art ultrahigh field (UHF) magnetic resonance (MR) protocol of the brain at 7.0 Tesla in ...