Skip to main content

Advertisement

Log in

Fluid mechanics of blood flow in human fetal left ventricles based on patient-specific 4D ultrasound scans

  • Original Paper
  • Published:
Biomechanics and Modeling in Mechanobiology Aims and scope Submit manuscript

Abstract

The mechanics of intracardiac blood flow and the epigenetic influence it exerts over the heart function have been the subjects of intense research lately. Fetal intracardiac flows are especially useful for gaining insights into the development of congenital heart diseases, but have not received due attention thus far, most likely because of technical difficulties in collecting sufficient intracardiac flow data in a safe manner. Here, we circumvent such obstacles by employing 4D STIC ultrasound scans to quantify the fetal heart motion in three normal 20-week fetuses, subsequently performing 3D computational fluid dynamics simulations on the left ventricles based on these patient-specific heart movements. Analysis of the simulation results shows that there are significant differences between fetal and adult ventricular blood flows which arise because of dissimilar heart morphology, E/A ratio, diastolic–systolic duration ratio, and heart rate. The formations of ventricular vortex rings were observed for both E- and A-wave in the flow simulations. These vortices had sufficient momentum to last until the end of diastole and were responsible for generating significant wall shear stresses on the myocardial endothelium, as well as helicity in systolic outflow. Based on findings from previous studies, we hypothesized that these vortex-induced flow properties play an important role in sustaining the efficiency of diastolic filling, systolic pumping, and cardiovascular flow in normal fetal hearts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • Ahmed BI (2014) The new 3D/4D based spatio-temporal imaging correlation (STIC) in fetal echocardiography: a promising tool for the future. J Matern Fetal Neonatal Med 27:1163–1168

    Article  Google Scholar 

  • Bellhouse B (1972) Fluid mechanics of a model mitral valve and left ventricle. Cardiovasc Res 6:199–210

    Article  Google Scholar 

  • Bombardini T et al (2008) Diastolic time-frequency relation in the stress echo lab: filling timing and flow at different heart rates. Cardiovasc Ultrasound 6:15

    Article  Google Scholar 

  • Chang C-H, Chang F-M, Yu C-H, Liang R-I, Ko H-C, Chen H-Y (2000) Systemic assessment of fetal hemodynamics by Doppler ultrasound. Ultrasound Med Biol 26:777–785

    Article  Google Scholar 

  • Chung M-W, Tsoutsman T, Semsarian C (2003) Hypertrophic cardiomyopathy: from gene defect to clinical disease. Cell Res 13:9–20

    Article  Google Scholar 

  • Davies PF, Remuzzi A, Gordon EJ, Dewey CF, Gimbrone MA (1986) Turbulent fluid shear stress induces vascular endothelial cell turnover in vitro. Proc Natl Acad Sci 83:2114–2117

    Article  Google Scholar 

  • DeVore G, Falkensammer P, Sklansky M, Platt L (2003) Spatio-temporal image correlation (STIC): new technology for evaluation of the fetal heart. Ultrasound Obstet Gynecol 22:380–387

    Article  Google Scholar 

  • Duran C, Angell WW, Johnson AD (2013) Recent progress in mitral valve disease. Elsevier, Amsterdam

    Google Scholar 

  • Elaz MS, Calkoen EE, Westenberg JJ, Lelieveldt BP, Roest AA, van der Geest RJ (2014) Vortex flow during early and late left ventricular filling in normal subjects: quantitative characterization using retrospectively-gated 4D flow cardiovascular magnetic resonance and three-dimensional vortex core analysis. J Cardiovasc Magn Reson 16:78

    Article  Google Scholar 

  • Fortini S, Querzoli G, Espa S, Cenedese A (2013) Three-dimensional structure of the flow inside the left ventricle of the human heart. Exp Fluids 54:1–9

    Article  Google Scholar 

  • Fry DL (1968) Acute vascular endothelial changes associated with increased blood velocity gradients. Circ Res 22:165–197

    Article  Google Scholar 

  • Ghosh E, Shmuylovich L, Kovács SJ (2010) Vortex formation time-to-left ventricular early rapid filling relation: model-based prediction with echocardiographic validation. J Appl Physiol 109:1812–1819

    Article  Google Scholar 

  • Godfrey M, Messing B, Cohen S, Valsky D, Yagel S (2012) Functional assessment of the fetal heart: a review. Ultrasound Obstet Gynecol 39:131–144

    Article  Google Scholar 

  • Groenenberg I, Stijnen T, Wladimiroff J (1990) Blood flow velocity waveforms in the fetal cardiac outflow tract as a measure of fetal well-being in intrauterine growth retardation. Pediatr Res 27:379–382

  • Groenendijk BC, Hierck BP, Vrolijk J, Baiker M, Pourquie MJ, Gittenberger-de Groot AC, Poelmann RE (2005) Changes in shear stress-related gene expression after experimentally altered venous return in the chicken embryo. Circ Res 96:1291–1298

    Article  Google Scholar 

  • Heiberg E, Ebbers T, Wigström L, Karlsson M (2003) Three-dimensional flow characterization using vector pattern matching. IEEE Trans Vis Comput Graph 9:313–319

    Article  Google Scholar 

  • Hogers B, DeRuiter M, Baasten A, Gittenberger-de Groot A, Poelmann R (1995) Intracardiac blood flow patterns related to the yolk sac circulation of the chick embryo. Circ Res 76:871–877

    Article  Google Scholar 

  • Holmes WM, McCabe C, Mullin JM, Condon B, Bain MM (2008) Noninvasive self-gated magnetic resonance cardiac imaging of developing chick embryos in ovo. Circulation 117:e346–e347

    Article  Google Scholar 

  • Hove JR, Köster RW, Forouhar AS, Acevedo-Bolton G, Fraser SE, Gharib M (2003) Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis. Nature 421:172–177

    Article  Google Scholar 

  • Jeong J, Hussain F (1995) On the identification of a vortex. J Fluid Mech 285:69–94

  • Johnson BM, Garrity DM, Dasi LP (2013) Quantifying function in the early embryonic heart. J Biomechan Eng 135:041006

    Article  Google Scholar 

  • Johnson P, Maxwell D, Tynan M, Allan L (2000) Intracardiac pressures in the human fetus. Heart 84:59–63

    Article  Google Scholar 

  • Kilner PJ, Yang GZ, Mohiaddin RH, Firmin DN, Longmore DB (1993) Helical and retrograde secondary flow patterns in the aortic arch studied by three-directional magnetic resonance velocity mapping. Circulation 88:2235–2247

    Article  Google Scholar 

  • Le TB, Sotiropoulos F (2012) On the three-dimensional vortical structure of early diastolic flow in a patient-specific left ventricle. Eur J Mech B Fluids 35:20–24

    Article  Google Scholar 

  • Liu S, Masliyah JH (1993) Axially invariant laminar flow in helical pipes with a finite pitch. J Fluid Mech 251:315–353

    Article  MATH  Google Scholar 

  • Mäkikallio K et al (2006) Fetal Aortic valve stenosis and the evolution of hypoplastic left heart syndrome patient selection for fetal intervention. Circulation 113:1401–1405

    Article  Google Scholar 

  • Marian A, Salek L, Lutucuta S (2001) Molecular genetics and pathogenesis of hypertrophic cardiomyopathy. Minerva medica 92:435

  • Markl M et al (2005) Time-resolved three-dimensional magnetic resonance velocity mapping of aortic flow in healthy volunteers and patients after valve-sparing aortic root replacement. J Thorac Cardiovasc Surg 130:456–463

    Article  Google Scholar 

  • Maron BJ, Anan TJ, Roberts WC (1981) Quantitative analysis of the distribution of cardiac muscle cell disorganization in the left ventricular wall of patients with hypertrophic cardiomyopathy. Circulation 63:882–894

    Article  Google Scholar 

  • Maron BJ, Sato N, Roberts WC, Edwards JE, Chandra RS (1979) Quantitative analysis of cardiac muscle cell disorganization in the ventricular septum. Comparison of fetuses and infants with and without congenital heart disease and patients with hypertrophic cardiomyopathy. Circulation 60:685–696

    Article  Google Scholar 

  • Marshall AC et al (2004) Creation of an atrial septal defect in utero for fetuses with hypoplastic left heart syndrome and intact or highly restrictive atrial septum. Circulation 110:253–258

    Article  Google Scholar 

  • Martínez-Legazpi P et al (2014) Contribution of the diastolic vortex ring to left ventricular filling. J Am Coll Cardiol 64:1711–1721

    Article  Google Scholar 

  • Olesen S-P, Claphamt D, Davies P (1988) Haemodynamic shear stress activates a K+ current in vascular endothelial cells. Nature 331:168–170

    Article  Google Scholar 

  • Pagon RA et al (2014) Hypertrophic cardiomyopathy overview

  • Pasipoularides A (2009) Heart’s vortex: intracardiac blood flow phenomena. PMPH-USA

  • Pasipoularides A (2012) Diastolic filling vortex forces and cardiac adaptations: probing the epigenetic nexus. Hellenic J Cardiol 53:458–469

    Google Scholar 

  • Pasipoularides A (2013) Evaluation of right and left ventricular diastolic filling. J Cardiovasc Transl Res 6:623–639

    Article  Google Scholar 

  • Pasipoularides A, Murgo JP, Miller JW, Craig WE (1987) Nonobstructive left ventricular ejection pressure gradients in man. Circ Res 61:220–227

    Article  Google Scholar 

  • Pedrizzetti G, Domenichini F (2014) Left ventricular fluid mechanics: the long way from theoretical models to clinical applications. Ann Biomed Eng 43:26–40

    Article  Google Scholar 

  • Raz D, Zaretsky U, Einav S, Elad D (2005) Cellular alterations in cultured endothelial cells exposed to therapeutic ultrasound irradiation. Endothelium 12:201–213

    Article  Google Scholar 

  • Taddei F, Franceschetti L, Signorelli M, Prefumo F, Fratelli N, Frusca T, Groli C (2007) Spatio-Temporal Imaging Correlation (STIC) in fetal echocardioraphy

  • Tobita K, Keller BB (2000) Right and left ventricular wall deformation patterns in normal and left heart hypoplasia chick embryos. Am J Physiol Heart Circ Physiol 279:H959–H969

    Google Scholar 

  • Tulzer G, Khowsathit P, Gudmundsson S, Wood DC, Tian Z-Y, Schmitt K, Huhta JC (1994) Diastolic function of the fetal heart during second and third trimester: a prospective longitudinal Doppler-echocardiographic study. Eur J Pediatr 153:151–154

    Article  Google Scholar 

  • Tworetzky W et al (2004) Balloon dilation of severe aortic stenosis in the fetus potential for prevention of hypoplastic Left Heart Syndrome: Candidate selection technique, and results of successful intervention. Circulation 110:2125–2131

  • Wang Y, Dur O, Patrick MJ, Tinney JP, Tobita K, Keller BB, Pekkan K (2009) Aortic arch morphogenesis and flow modeling in the chick embryo. Ann Biomed Eng 37:1069–1081

  • Wigström L, Ebbers T, Fyrenius A, Karlsson M, Engvall J, Wranne B, Bolger AF (1999) Particle trace visualization of intracardiac flow using time-resolved 3D phase contrast MRI. Magn Reson Med 41:793–799

    Article  Google Scholar 

  • Yamashita S et al (2007) Visualization of hemodynamics in intracranial arteries using time-resolved three-dimensional phase-contrast MRI. J Magn Reson Imaging 25:473–478

    Article  Google Scholar 

  • Yang Q, Sanbe A, Osinska H, Hewett TE, Klevitsky R, Robbins J (1998) A mouse model of myosin binding protein C human familial hypertrophic cardiomyopathy. J Clin Investig 102:1292

    Article  Google Scholar 

  • Yap CH, Liu X, Pekkan K (2014) Characterization of the vessel geometry, flow mechanics and wall shear stress in the great arteries of wildtype prenatal mouse. PloS One 9(1):e86878

Download references

Acknowledgments

The authors would like to thank Singapore Ministry of Health, National Medical Research Council Grant Number NMRC/BNIG/2020/2014 (PI: Yap) for funding.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Choon Hwai Yap.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (mp4 2178 KB)

Supplementary material 2 (mp4 1820 KB)

Supplementary material 3 (mp4 1322 KB)

Supplementary material 4 (mp4 1043 KB)

Supplementary material 5 (mp4 1839 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lai, C.Q., Lim, G.L., Jamil, M. et al. Fluid mechanics of blood flow in human fetal left ventricles based on patient-specific 4D ultrasound scans. Biomech Model Mechanobiol 15, 1159–1172 (2016). https://doi.org/10.1007/s10237-015-0750-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10237-015-0750-5

Keywords

Navigation