Reference Ranges of Blood Flow in the Major Vessels of the Normal Human Fetal Circulation at Term by Phase Contrast Magnetic Resonance Imaging Prsa et al: Normal Fetal Flows by PC MRI Milan Prsa 1 , MD; Liqun Sun 1 , MD; Joshua van Amerom 2 , BASc; Shi-Joon Yoo 2 , MD; Lars Grosse-Wortmann 1 , MD; Edgar Jaeggi 1 , MD; Christopher Macgowan 3 , PhD; Mike Seed 1,2 , MD 1 Division of Pediatric Cardiology, Department of Pediatrics, University of Toronto and Hospital for Sick Children, Toronto, Canada 2 Department of Diagnostic Imaging, University of Toronto and Hospital for Sick Children, Toronto, Canada 3 Department of Physiology and Experimental Medicine, University of Toronto and Hospital for Sick Children, Toronto, Canada Correspondence to Mike Seed Division of Paediatric Cardiology Department of Pediatrics, Hospital for Sick Children 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada Fax: 416-813-7547 Tel: 416-813-7654 ext. 204067 Email: [email protected]DOI: 10.1161/CIRCIMAGING.113.001859 Journal Subject Codes: [6] Cardiac development, [30] CT and MRI, [41] Pediatric and congenital heart disease, [156] Pulmonary biology and circulation. v v v v v er ersi si si i si ity ty o o o o o o f f To To To o o o oro ro ro ro ro ro ron n g k s a gno no o no n stic Ima ma ma a agi gi ging ng ng g ng, Un Un Un Un Univ iv iv iv ive e er e e si si sity o o of T T Tor r r r ro o o on o to to to to to a and nd n H H H H Hos s s s spi pi pi pi pita ta ta ta tal l l l l fo fo fo f for r r r r Si Si Si Si Sick c c c c siology y y y a a a a and nd nd nd nd E E E E Exp x xp xp x er er er er erim im im im imen en en en enta a a a al l l l l Me Me Me Me Medi di di di di ci ci ci ci cine ne ne n , , , Un Un Un Un Univ iv v v ver er er er ersi si si si sity ty ty ty ty o o o o of f f f f To To To To Toro r r r nto a by guest on April 22, 2018 http://circimaging.ahajournals.org/ Downloaded from
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Reference Ranges of Blood Flow in the Major Vessels of the Normal Human Fetal
Circulation at Term by Phase Contrast Magnetic Resonance Imaging
Prsa et al: Normal Fetal Flows by PC MRI
Milan Prsa1, MD; Liqun Sun1, MD; Joshua van Amerom2, BASc;
Shi-Joon Yoo2, MD; Lars Grosse-Wortmann1, MD; Edgar Jaeggi1, MD;
Christopher Macgowan3, PhD; Mike Seed1,2, MD
1Division of Pediatric Cardiology, Department of Pediatrics, University of Toronto and Hospital
for Sick Children, Toronto, Canada
2Department of Diagnostic Imaging, University of Toronto and Hospital for Sick Children,
Toronto, Canada
3Department of Physiology and Experimental Medicine, University of Toronto and Hospital for
Sick Children, Toronto, Canada
Correspondence to Mike Seed Division of Paediatric Cardiology Department of Pediatrics, Hospital for Sick Children 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada Fax: 416-813-7547 Tel: 416-813-7654 ext. 204067 Email: [email protected]
DOI: 10.1161/CIRCIMAGING.113.001859
Journal Subject Codes: [6] Cardiac development, [30] CT and MRI, [41] Pediatric and
congenital heart disease, [156] Pulmonary biology and circulation.
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proximal to any portal vein branches. The image parameters used for the PC MRI acquisitions
were as follows: slice thickness 5mm, field of view 240 mm, phase field of view 100% + 33%
phase oversampling, matrix size 192×192, voxel size 1.25×1.25×5 mm, echo time 2.92 ms,
repetition time 6.55 ms, flip angle 20°, 1 average and 4 views per segment. This results in a
temporal resolution of ~ 50 ms giving approximately 10 true cardiac phases, which were
interpolated to 15 calculated phases. A velocity sensitivity (VENC) of 150 cm/s was used for the
AAo, MPA, DAo, DA; 100 cm/s for the SVC, RPA and LPA; and 50 cm/s for the UV. A typical
scan time for each vessel was 34 seconds, with a total scan time of approximately 30 minutes.
Using software created in our laboratory (MATLAB, MathWorks, USA) the correct R-R
intervals for each acquisition were determined retrospectively by MOG using raw data acquired
at an R-R interval of 545ms to ensure fetal heart rates down to 110 bpm were adequately
oversampled for correct reconstruction. The details of MOG are given in previous publications
(5,7). The reconstructed images were post-processed on a commercial software package for flow
quantification (Q-flow 5.2, Medis Medical Imaging Systems, Leiden, Netherlands). The total
post-processing time for each study including fetal weight estimation was approximately 90
minutes.
The morphology of the fetal hearts was assessed at the initial echocardiogram using a
segmental sequential analysis of the anatomy (13). At follow up echocardiography we measured
the mitral, tricuspid, aortic, and pulmonary valve dimensions and the end-diastolic diameters of
the right and left ventricles according to previously published techniques (14). Z-scores were
calculated for each of these structures. The morphology of the interatrial septum was assessed
and size of the foramen ovale measured. Each subject underwent Doppler assessment of the
umbilical artery, umbilical vein, middle cerebral artery and ductus venosus. As newborns, the
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ventricular septal defect and one because no Dopplers were recorded. Complete
echocardiograms and a complete set of MRI flow measurements were obtained in all of the
remaining 40 subjects. All 40 of these fetuses were subsequently born at term with normal birth
weights and there were no significant perinatal complications or postnatal medical problems
identified. MRI was performed at a mean gestational age of 37 weeks (SD 1.1 weeks) with a
mean fetal weight of 3.0 kg (SD 0.5 kg).
The first five fetuses had repeat PC MRI measurements made in each of the vessels. The
comparison reveals good reproducibility with no significant bias (r = 0.96, p = <0.0001, bias -
10.8, SD of bias 71.3 ml/min), as shown in Figure 1. Measurements made in the last ten fetuses
were examined for inter-observer correlation and showed good agreement with no significant
bias (r = 0.97, p = 0.0001, bias = -21.2, SD of bias 48.3 ml/min) (Figure 2). In this same group
of ten fetuses, the MRI measurements correlated reasonably well with US measurements of flow
in the MPA and AAo (r = 0.77, p = 0.0001), with a small bias of 26 ml/min for higher flows by
ultrasound (SD of bias 98.6 ml/min) (Figure 3). The assessment of internal validation between
MRI flow measurements through comparison of direct and indirect measurements of PBF for the
whole study group also revealed reasonable agreement with no significant bias (r = 0.43, p =
0.004, bias = 10.5, SD of bias 56.0 ml/min/kg), as shown in Figure 4.
The results of the flow measurements are shown in Table 1 and Figures 5 and 6, with a
full table of individual flows and cardiac morphology included in the supplementary information.
The mitral, tricuspid, aortic and pulmonary valves and right and left ventricular diameters were
all with two standard deviations of the mean. A significant inverse correlation was found
between FO flow and PBF (r = -0.64, p = <0.0001) as shown in Figure 7. We found a moderate
correlation between the ratio of MPA to AAo flow by MRI and the ratio of right to left
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Other modifications in the human estimates reported in the more recent edition of
Rudolph’s text result in significant differences compared with the MRI results, including lower
DA, FO, and DAo flows and higher PBF flow. The modifications are reportedly an attempt to
accommodate subsequent human ultrasound results. However, as acknowledged by Rudolph,
ultrasound measurements of flow are prone to potential inaccuracies arising from problems with
vessel diameter measurement, flow alignment and the inability to account for the different
velocities across the lumen of the vessel (15). In our study, the US flow measurements were
consistently slightly higher than the MRI measurements, which may be due to the fact that our
ultrasound technique assumed a constant flow velocity across the vessel lumen, where in reality
flow was likely slower around the vessel periphery than in the middle of the vessel where it was
sampled. In addition to intrinsic inaccuracies in our US and MRI measurements, we are also
aware of the possibility that although the two techniques were performed on the same day,
changes in the physiologic state of the fetus during and between the MRI and US could have
affected their agreement.
Differences in sampling techniques may explain the wide variation in results obtained in
different human ultrasound studies. For example, Rasenen found an RV/LV output ratio of 1.5
in late gestation fetuses, compared with a ratio of 1.08 at term in De Smedt’s study (27,28). Our
results indicate a ratio of 1.27, in keeping with the 1.28 found by Kenny (16). Estimates of mean
CVO range from 425 ml/min/kg to 553 ml/min/kg, although most estimates are approximately
450 ml/min/kg, which is in keeping with the MRI result of 465 ml/min/kg (29). The good
correlation we found between the ratio of MPA by AAo flow by MRI with echocardiographic
measurements of the ratio of the right and left ventricular end diastolic dimensions was a
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reassuring demonstration of congruent physiologic and morphologic parameters of the relative
dominance of each ventricle with respect to the CVO by two different imaging modalities.
Previous ultrasound measurements of mean fetal PBF range from 47 ml/min/kg or 11%
of CVO in Mielke’s large cohort to 25% of CVO in third trimester fetuses in Rasanen’s study
(27,30). One reason for the wide range of PBF found by different authors might be the different
measurement techniques used, as in the majority of studies the PBF is calculated by subtraction
of the DA flow from the MPA. Rasanen used direct ultrasound measurements of PBF and found
that PBF increased from 13% at 20 weeks to ~ 25% of CVO at 30 weeks and then dropped again
to ~ 20% of CVO by 38 weeks (27). Rasanen’s results indicate that the increase in PBF seen in
the third trimester was associated with a reduction in FO shunt but no change in AAo flow. This
inverse relationship between PBF and FO shunt was also seen in our study, although in our case
the variation in PBF and FO flow was seen in fetuses of the same gestational age. In Rasanen’s
study, there was an approximately 2-3 fold range in PBF at 37 weeks, while in our own study,
the range of PBF was higher with at least a ten-fold difference between the subject with the
lowest PBF of 13 ml/kg/min or 2% of CVO and the highest PBF of 187 ml/min/kg or 30% of
CVO. The reason for this discrepancy is not clear. Rasanen reports a higher level of agreement
between direct and indirect measurements of PBF using US than we obtained using MRI, raising
the possibility that inaccuracy of the MRI measurements could have resulted in the discrepancy.
The pulmonary arteries are certainly the smallest vessels we measured by MRI, and are at the
lower limit of size for established criteria for PC MRI accuracy (22). However, it is also
possible that the sample size had an influence, as although Rasanen’s study included 63 patients,
these were evenly distributed across a gestational age range of 18 to 40 weeks, while our own 40
subjects were concentrated around the same gestational age of 37 weeks. The wider range of
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streaming of the umbilical venous return, which by convention is preferentially directed through
the ductus venosus and left lobe of the liver to form a high velocity stream in the leftward
posterior aspect of the IVC which is directed towards the FO (17). In fetal lambs, this
mechanism maintains a higher oxygen content of the blood in the left heart than the right,
although the wide variation in the FO shunt seen our study suggests this mechanism may be
subject to some variation.
Strengths and limitations
Although this study establishes provisional reference ranges for MRI flows, the sample size of
40 is too small to establish normal ranges. However, one strength of our study compared with
previous ultrasound studies is that flow was measured in each of the large vessels. This allows
for characterization of distribution of the whole fetal circulation, which has been a conceptually
helpful aspect of the fetal lamb research and permits internal validation of the measurements.
Our reference ranges are indexed by fetal weight rather than gestational age. This allows for
comparison with the lamb measurements and is made possible by the high accuracy of fetal
weight measurement by MR segmentation at term (40). Our study differs from the majority of
ultrasound studies, because all of the subjects were studied during a short gestational age
window. While this might be regarded as a limitation, we would argue that it allows for a more
homogeneous study group, focusing on a period of the pregnancy when PC MRI is less prone to
movement artifact but when sonographic windows are more limited. However, we wish to
emphasize that our results can only be applied to the late gestation human fetus. Furthermore,
our technique is not currently suitable for studying fetuses at younger gestational ages because of
the inherent difficulties encountered with imaging small moving structures using MRI. The
MRI flows, theheheeheee s
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fetal lamb research and permits internal validation of the me
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vulnerability of MRI to movement artifact resulting from fetal motion represents a significant
drawback of the technique compared with ultrasound.
Conclusion
This study provides a comprehensive set of measurements of blood flow in the major vessels of
the late gestation human fetal circulation. The results are consistent with a previous estimate of
human fetal flows based on detailed measurements made in fetal lambs using radioactive
microspheres and provide a preliminary set of reference data for future MRI and ultrasound
measurements of the fetal circulation. A new observation was the wide range and inverse
relationship of PBF and FO shunt amongst fetuses of the same gestational age. We propose that
the mechanism and implications of this finding deserve further investigation.
Acknowledgements
We would like to thank Luke Itani for his illustration for Figure 6.
Sources of Funding
This research was funded by a grant awarded by the Labbatt Family Innovations Fund
Disclosures
None.
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1. Fratz S, Chung T, Greil GF, Samyn MM, Taylor AM, Valangiacomo Beuchel ER, Yoo S-J, Powell AJ. Guidelines and protocols for cardiovascular magnetic resonance in children and adults with congenital heart disease: SCMR expert group on congenital heart disease. J Cardiovas Magn Reson. 2013; 15:51.
2. Yamamura J, Frish M, Ecker H, Graessner J, Hecher K, Adam G, Wedegartner U. Self-gating MR imaging of the fetal heart: comparison with real cardiac triggering. EurRadiol. 2011;21:142-149.
3. Yamamura J, Kopp I, Frisch M, Fischer R, Valett K, Hecher K, Adam G, Wedergartner U. Cardiac MRI of the fetal heart using a novel triggering method: initial results in an animal model. J Magn Reson Imaging. 2012;35:1071-1076.
4. Schoennagel BP, Remus CC, Yamamura J, Kording F, de Sousa MT, Hecher K, Fischer R, Ueberle F, Boehme M, Adam G, Kooijman H, Wedergartner U. Fetal blood flow velocimetry by phase-contrast MRI using a new triggering method and comparison with Doppler ultrasound in a sheep model: a pilot study. MAGMA. 2013. doi: 10.1007/s10334-013-0397-0.
5. Jansz M, Seed M, van Amerom, Wong D, Grosse-Wortmann L, Yoo SJ, Macgowan CK. Metric optimized gating for fetal cardiac MRI. Magn Reson Med. 2010; 64:1304-1314.
6. Roy CW, Seed M, van Amerom JFP, Al Nafisi B, Grosse-Wortmann L, Yoo S-J, Macgowan CK. Dynamic imaging of the fetal heart using metric optimized gating. Magn Reson Med. 2013;70:1598-1607.
7. Seed M, van Amerom JFP, Yoo SJ, Al Nafisi B, Grosse-Wortmann L, Jaeggi E, Jansz MS, Macgowan CK. Feasibility of quantification of the distribution of blood flow in the normal human fetal circulation using CMR: a cross-sectional study. J Cardiovas Magn Reson. 2012;26:14.
8. Al Nafisi B, van Amerom JFP, Forsey J, Jaeggi E, Grosse-Wortmann L, Yoo SJ, Macgowan CK, Seed M. Fetal circulation in left-sided congenital heart disease measured by cardiovascular magnetic resonance: a case-control study. J Cardiovas Magn Reson.2013;15:65.
9. Porayette P, van Amerom JFP, Yoo SJ, Macgowan CK, Seed M. MRI shows limited mixing between systemic and pulmonary circulations – a potential cause of in utero pulmonary vascular disease. Cardiol Young. In-press.
10. Van Amerom JFP, Roy CW, Prsa M, Kingdom, JC, Macgowan CK, Seed M. Assessment of Late-Onset Fetal Growth Restriction by Phase Contrast MR. Abstract. Proc Int Soc Mag Reson Med 21. 2013.4129.
11. Lai WW, Geva T, Shirali GS, Frommelt PC, Humes RA, Brook MM, Pignatelli RC, Rychick J. Guidelines and standards for performance of a pediatric echocardiogram: a report from the task force of the Pediatric Council of the American Society of Echocardiography. J Am Soc Echocardiogr. 2006;19:1413-1430.
12. Baker PN, Johnson IR, Gowland PA, Hykin J, Harvey PR, Freeman A, Adams V, Mansfield P, Worthington BS. Fetal weight estimation by echo-planar magnetic resonance imaging. Lancet. 1994;343:644-645.
13. Yoo SJ, Lee YH, Cho KS, Kim DY. Sequential segmental analysis of fetal congenital heart disease. Cardiol Young. 1999;9:430-444.
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ed M, van Amerom JFP, Al N fisi B, Grosse-Wortmann L YC z
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wan CK. Feeeeeasasasaasibibibibibilililili ititiii yyyy ofofofofof qqqqquauauauauantntntntntifififificicicaaaaatititititionoonono oooof ff f f thththththeeeee didididdistststststririririribubbbb tion of bananan fffetetetalalal cccirirircucuculalalatititiononon uuusisisinnng g g gg CMCMCMR:R:R: aaa cccrororooossssss ss-sececectititiionononalalall ssstututudydydyy. JJJ CaCaCa;2;2;26:6:6:141414
14. Schneider C, McCrindle BW, Carvalho JS, Hornberger LK, McCarthy KP, Daubeney PEF. Development of Z-scores for fetal cardiac dimensions from echocardiography. Ultrasound Obstet Gynecol. 2005;26:599-605.
15. Gill RW. Measurement of blood flow by ultrasound: accuracy and sources of error.Ultrasound Med Bio. 1985;7:625-42.
16. Kenny JF, Plappert T, Doublilet P, Saltzman DH, Cartier M, Zollars L, Leatherman GF, St John Sutton MG. Changes in intra-cardiac blood flow velocities and right and left ventricular stroke volumes with gestational age in the normal human fetus: a prospective Doppler echocardiographic study. Circulation. 1986;60:338-342.
17. Rudolph AM. Congenital Diseases of the Heart: Clinical-Physiological Considerations.2nd edition. Chichester: Wiley Blackwell, 2001.
18. Han SP. A Globally Convergent Method for Nonlinear Programming. Journal of Optimization Theory and Applications. 1977;22:297-309.
19. Powell MJD. A Fast Algorithm for Nonlinearly Constrained Optimization Calculations. Lecture notes in mathematics. 1978;630:144-157.
20. Mangasarian OL, Meyer RR, Robinson SM. The Convergence of Variable Metric Methods for Nonlinearly Constrained Optimization Calculations, in Nonlinear programming 3. London and New York: Academic Press, 1978.
21. Lotz J, Meier C, Leppert A, Galanski M. Cardiovascular Flow Measurement with Phase-Contrast MR Imaging: Basic Facts and Implementation. Radiographics. 2002;22:651-671.
22. Hofman MBM, Visser FC, Van Rossum AC, Vink GQM, Sprenger M, Westerhof N. In vivo validation of magnetic resonance blood volume flow measurements with limited spatial resolution in small vessels. Magn Reson Med. 1995;33:778-784.
23. Rudolph AM, Heymann MA. The circulation of the fetus in utero: methods for studying distribution of blood flow, cardiac output, and organ blood flow. Circ Res. 1967;21:163-184.
24. Rudolph AM. Congenital Diseases of the Heart: Clinical-Physiological Considerations. 3rd edition. Chichester: Wiley Blackwell, 2009.
25. Van Lierde M, Oberweis D, Thomas K. Ultrasonic measurement of aortic and umbilical blood flow in the human fetus. Obstet Gynecol. 1984;63:801-805.
26. Sutton MG, Plapper T and Doubilet P. Relationship between placental blood flow and combined ventricular output with gestational age in normal human fetus. Cardiovasc Res. 1991;25:603-608.
27. Rasanen J, Wood DC, Weiner S, Ludomirski A, Huhta JC. Role of the pulmonary circulation in the distribution of the human fetal cardiac output during the second half of pregnancy. Circulation. 1996;94:1068-1073.
28. De Smedt MCH, Visser GHA, Meijboom, EF. Fetal cardiac output estimated by Doppler echocardiography during mid- and late gestation. Am J Cardiol. 1987;60:338-342.
29. St John Sutton M, Groves A and MacNeill A, Sharland G, Allan L. Assessment of changes in blood flow through the lungs and foramen ovale in the normal human fetus with gestational age: a prospective Doppler echocardiographic study. Br Heart J.1994;71:232-237.
30. Mielke G, Benda N. Cardiac Output and central distribution of blood flow in the human fetus. Circulation. 2001;103:1662-1668.
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31. Kiserud T, Ebbing C, Kessler J, Rasmussen S. Fetal cardiac output, distribution to the placenta and impact of placental compromise. Ultrasound Obstet Gynecol. 2006;28:126-136.
32. Phillipos EZ, Robertson MA, Still KD. The echocardiographic assessment of the human fetal foramen ovale. J Am Soc Echocardiography. 1994;7:257-263.
33. Naeye RL. Arterial changes during the perinatal period. Arch Pathol. 1961;71:121-128. 34. Noori S, Wlodaver A, Gottipati V, McCoy M, Schultz D, Escobedo M. Transitional
Changes in Cardiac and Cerebral Hemodynamics in Term Neonates at Birth. J Pediatr. 2012;160:943-948.
35. Konduri GG, Gervasio CT and Theodorou AA. Role of Adenosine Triphosphate and Adenosine in Oxygen-Induced Pulmonary Vasodilation in Fetal Lambs. Pediatr Res. 1993;33:533-539.
36. Rasanen J, Wood DC, Debbs RH, Cohen J, Weiner S, Huhta JC. Reactivity of the Human Fetal Pulmonary Circulation to Maternal Hyperoxygenation Increases During the Second Half of Pregnancy - A Randomized Study. Circulation. 1998;97:257-262.
37. Gregg AR, Weiner CP. "Normal" Umbilical Arterial and Venous Acid-Base and Blood Gas Values. Clin Obstet Gynecol. 1993;36:24-32.
38. Wedergartner U, Kooijman H, Yamamura J, Frisch M, Weber C, Buchert R, Huff A, Hecher K, Adam G. In vivo measurement of fetal blood oxygen saturation in cardiac ventricles of fetal sheep: a feasibility study. Magn Reson Med. 2010;64:32-41.
39. Sun L, Al-Rujaib M, van Amerom JFP, Macgowan CK, Seed M. Comprehensive assessment of late gestation human fetal circulation by phase contrast MRI and T2 mapping. Abstract. Proc Int Soc Mag Reson Med 22. 2014.8084.
40. Zaretsky M, Reichel TF, McIntire DD, Twickler DM. Comparison of magnetic resonance imaging to ultrasound in the estimation of birthwieght at term. Am J Obstet Gynecol.2003;189:1017-1020.
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Table 1. Means, standard deviations and reference ranges (mean ± 2SD) of flows in 40 normal late gestation human fetuses measured by phase contrast MRI
expressed in ml/min/kg and as percentages and as modeled mean percentages of the combined ventricular output. CVO – combined ventricular output, MPA -
main pulmonary artery, AAo – ascending aorta, SVC – superior vena cava, DA – ductus arteriosus, PBF – pulmonary blood flow, DAo – descending aorta, FO –
foramen ovale. FO flow was calculated as the difference between the left ventricular output and pulmonary blood flow.
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