Skip to main content
SpringerLink
Log in

Assessment of BOLD response in the fetal lung

  • Paediatric
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objective

Assessment of lung development and maturity is of utmost importance in prenatal counseling. Blood oxygen level–dependent (BOLD) effect MRI was developed for functional evaluations of organs. To date, no data are available in fetal lungs and nothing is known about the existence of a BOLD effect in the lungs. The aim of our study was to evaluate if a BOLD response could be detected in fetal lungs.

Materials and methods

From January 2014 to December 2016, 38 healthy pregnant women were prospectively enrolled. After a routine scan on a 1.5-T MRI device (normoxic period), maternal hyperoxia was induced for 5 min before the BOLD sequence (hyperoxic period). R2* was evaluated by fitting average intensity of the signal, both for normoxic (norm) and hyperoxic (hyper) periods.

Results

A significant BOLD response was observed after maternal hyperoxia in the lungs with a mean R2* decrease of 12.1 ± 2.5% (p < 0.001), in line with the placenta response with a mean R2* decrease of 19.2 ± 5.9% (p < 0.0001), confirming appropriate oxygen uptake. Conversely, no significant BOLD effect was observed for the brain nor the liver with a mean ∆R2* of 3.6 ± 3.1% (p = 0.64) and 2.8 ± 3.7% (p = 0.23).

Conclusion

This study shows for the first time in human that a BOLD response can be observed in the normal fetal lung despite its prenatal “non-functional status.” If confirmed in congenital lung and chest malformations, this property could be used in addition to the lung volume for a better prediction of postnatal respiratory status.

Key Points

• Blood oxygen level–dependent (BOLD) effect MRI was developed for functional evaluations of organs and could have interesting implications for the fetal organs.

• Assessment of lung development is of utmost importance in prenatal counseling, but to date no data are available in fetal lungs.

• BOLD response can be observed in the normal fetal lung opening the way to studies on fetus with pathological lungs.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

BOLD:

Blood oxygen level–dependent

GA:

Gestational age

LHR:

Lung-to-head ratio

MRI:

Magnetic resonance imaging

ROI:

Regions of interest

SEM:

Standard error to the mean

TE:

Echo time effective

TR:

Repetition

References

  1. Marshall J, Salemi JL, Tanner JP et al (2015) Prevalence, correlates, and outcomes of omphalocele in the United States, 1995-2005. Obstet Gynecol 126(2):284–293

    Article  Google Scholar 

  2. Morris JK, Springett AL, Greenlees R et al (2018) Trends in congenital anomalies in Europe from 1980 to 2012. PLoS One 13(4):e0194986

    Article  Google Scholar 

  3. Ramakrishnan R, Salemi JL, Stuart AL et al (2018) Trends, correlates, and survival of infants with congenital diaphragmatic hernia and its subtypes. Birth Defects Res 6

  4. Donn SM, Sinha SK (2017) Pulmonary diagnostics. Semin Fetal Neonatal Med 22(4):200–205

    Article  Google Scholar 

  5. Quinn TM, Hubbard AM, Adzick NS (1998) Prenatal magnetic resonance imaging enhances fetal diagnosis. J Pediatr Surg 33(4):553–558

    Article  CAS  Google Scholar 

  6. Debus A, Hagelstein C, Kilian AK et al (2013) Fetal lung volume in congenital diaphragmatic hernia: association of prenatal MR imaging findings with postnatal chronic lung disease. Radiology. 266(3):887–895

    Article  Google Scholar 

  7. Jani J, Cannie M, Sonigo P et al (2008) Value of prenatal magnetic resonance imaging in the prediction of postnatal outcome in fetuses with diaphragmatic hernia. Ultrasound Obstet Gynecol 32:793–799

    Article  CAS  Google Scholar 

  8. Shieh HF, Barnewolt CE, Wilson JM et al (2017) Percent predicted lung volume changes on fetal magnetic resonance imaging throughout gestation in congenital diaphragmatic hernia. J Pediatr Surg 52(6):933–937

    Article  Google Scholar 

  9. Vergani P (2012) Prenatal diagnosis of pulmonary hypoplasia. Curr Opin Obstet Gynecol 24(2):89–94

    Article  Google Scholar 

  10. Rubesova E (2016) Why do we need more data on MR volumetric measurements of the fetal lung? Pediatr Radiol 46(2):167–171

    Article  Google Scholar 

  11. Russo FM, Eastwood MP, Keijzer R et al (2017) Lung size and liver herniation predict need for extracorporeal membrane oxygenation but not pulmonary hypertension in isolated congenital diaphragmatic hernia: systematic review and meta-analysis. Ultrasound Obstet Gynecol 49:704–713

    Article  CAS  Google Scholar 

  12. Kasprian G, Balassy C, Brugger PC, Prayer D (2006) MRI of normal and pathological fetal lung development. Eur J Radiol 57(2):261–270

    Article  Google Scholar 

  13. Cannie M, Jani J, De Keyzer F, Roebben I, Breysem L, Deprest J (2011) T2 quantifications of fetal lungs at MRI-normal ranges. Prenat Diagn 31(7):705–711

    Article  CAS  Google Scholar 

  14. Terui K, Omoto A, Osada H et al (2011) Prediction of postnatal outcomes in congenital diaphragmatic hernia using MRI signal intensity of the fetal lung. J Perinatol 31(4):269–273

    Article  CAS  Google Scholar 

  15. Moshiri M, Mannelli L, Richardson ML, Bhargava P, Dubinsky TJ (2013) Fetal lung maturity assessment with MRI fetal lung-to-liver signal-intensity ratio. AJR Am J Roentgenol 201(6):1386–1390

    Article  Google Scholar 

  16. Lee W, Krisko A, Shetty A et al (2009) Non-invasive fetal lung assessment using diffusion-weighted imaging. Ultrasound Obstet Gynecol 34(6):673–677

    Article  CAS  Google Scholar 

  17. Yablonskiy DA, Sukstanskii AL, He X (2013) Blood oxygenation level-dependent (BOLD)-based techniques for the quantification of brain hemodynamic and metabolic properties - theoretical models and experimental approaches. NMR Biomed 26:963–986

    Article  CAS  Google Scholar 

  18. Cao J, Lu KH, Oleson ST et al (2019) Gastric stimulation drives fast BOLD responses of neural origin. Neuroimage. 15(197):200–211

    Article  Google Scholar 

  19. Niles DJ, Artz NS, Djamali A, Sadowski EA, Grist TM, Fain SB (2016) Longitudinal assessment of renal perfusion and oxygenation in transplant donor-recipient pairs using arterial spin labeling and blood oxygen level-dependent magnetic resonance imaging. Invest Radiol 51:113–120

    Article  CAS  Google Scholar 

  20. Grover S, Lloyd R, Perry R et al (2019) Assessment of myocardial oxygenation, strain, and diastology in MYBPC3-related hypertrophic cardiomyopathy: a cardiovascular magnetic resonance and echocardiography study. Eur Heart J Cardiovasc Imaging 20:932–938

    Article  Google Scholar 

  21. Lee J, Kim CK, Gu KW, Park W (2019) Value of blood oxygenation level-dependent MRI for predicting clinical outcomes in uterine cervical cancer treated with concurrentchemoradiotherapy. Eur Radiol. 29(11):6256–6265

    Article  Google Scholar 

  22. Siauve N, Chalouhi GE, Deloison B et al (2015) Functional imaging of the human placenta with magnetic resonance. Am J Obstet Gynecol 213(4 Suppl):S103–S114

    Article  Google Scholar 

  23. Huen I, Morris DM, Wright C et al (2013) R1 and R2 * changes in the human placenta in response to maternal oxygen challenge. Magn Reson Med 70(5):1427–1433

    Article  CAS  Google Scholar 

  24. Semple SI, Wallis F, Haggarty P et al (2001) The measurement of fetal liver T(*)(2) in utero before and after maternal oxygen breathing: progress towards a non-invasive measurement of fetal oxygenation and placental function. Magn Reson Imaging 19(7):921–928

    Article  CAS  Google Scholar 

  25. Sørensen A, Peters D, Simonsen C et al (2013) Changes in human fetal oxygenation during maternal hyperoxia as estimated by BOLD MRI. Prenat Diagn 33(2):141–145

    Article  Google Scholar 

  26. Luo J, Abaci Turk E, Bibbo C et al (2017) In vivo quantification of placental insufficiency by BOLD MRI: a human study. Sci Rep 7(1):3713

    Article  Google Scholar 

  27. Bland JM, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1(8476):307–310

    Article  CAS  Google Scholar 

  28. Chalouhi GE, Alison M, Deloison B et al (2013) Fetoplacental oxygenation in an intrauterine growth restriction rat model by using blood oxygen level-dependent MR imaging at 4.7 T. Radiology. 269(1):122–129

    Article  Google Scholar 

  29. Ingram E, Morris D, Naish J, Myers J, Johnstone E (2017) MR imaging measurements of altered placental oxygenation in pregnancies complicated by fetal growth restriction. Radiology. 285(3):953–960

    Article  Google Scholar 

  30. Kivilevitch Z, Salomon LJ, Yagel S, Achiron R (2011) Bowel circulation in normally grown and growth-restricted fetuses. J Ultrasound Med 30(11):1529–1537

    Article  Google Scholar 

  31. Godfrey KM, Haugen G, Kiserud T et al (2012) Fetal liver blood flow distribution: role in human developmental strategy to prioritize fat deposition versus brain development. PLoS One 7(8):e41759

    Article  CAS  Google Scholar 

  32. Stampalija T, Casati D, Monasta L et al (2016) Brain sparing effect in growth-restricted fetuses is associated with decreased cardiac acceleration and deceleration capacities: a case-control study. BJOG. 123(12):1947–1954

    Article  CAS  Google Scholar 

  33. Morton SU, Brodsky D (2016) Fetal physiology and the transition to extrauterine life. Clin Perinatol 43(3):395–407

    Article  Google Scholar 

  34. Wu TW, Azhibekov T, Seri I (2016) Transitional hemodynamics in preterm neonates: clinical relevance. Pediatr Neonatol 57(1):7–18

    Article  Google Scholar 

  35. DeKoninck P, Jimenez J, Russo FM, Hodges R, Gratacós E, Deprest J (2014) Assessment of pulmonary vascular reactivity to oxygen using fractional moving blood volume in fetuses with normal lung development and pulmonary hypoplasia in congenital diaphragmatic hernia. Prenat Diagn 34(10):977–981

    Article  CAS  Google Scholar 

  36. Schoennagel BP, Yamamura J, Fischer R et al (2015) BOLD MRI in the brain of fetal sheep at 3T during experimental hypoxia. J Magn Reson Imaging 41:110–116

    Article  Google Scholar 

  37. Sørensen A, Holm D, Pedersen M et al (2011) Left-right difference in fetal liver oxygenation during hypoxia estimated by BOLD MRI in a fetal sheep model. Ultrasound Obstet Gynecol 38(6):665–672

    Article  Google Scholar 

  38. Cannie M, Jani J, De Keyzer F, Roebben I, Dymarkowski S, Deprest J (2009) Diffusion-weighted MRI in lungs of normal fetuses and those with congenital diaphragmatic hernia. Ultrasound Obstet Gynecol 34(6):678–686

    Article  CAS  Google Scholar 

  39. Avni R, Golani O, Akselrod-Ballin A et al (2016) MR imaging-derived oxygen-hemoglobin dissociation curves and fetal-placental oxygen-hemoglobin affinities. Radiology. 280(1):68–77

    Article  Google Scholar 

  40. Sørensen A, Sinding M, Peters DA et al (2015) Placental oxygen transport estimated by the hyperoxic placental BOLD MRI response. Physiol Rep 3(10):e12582

    Article  Google Scholar 

  41. Nagao M, Yamasaki Y, Kawanami S et al (2017) Quantification of myocardial oxygenation in heart failure using blood-oxygen-level-dependent T2* magnetic resonance imaging: comparison with cardiopulmonary exercise test. Magn Reson Imaging 39:138–143

    Article  Google Scholar 

Download references

Acknowledgments

Analysis of MRI BOLD data was performed at the Life Imaging Facility of Paris Descartes University (Plateforme Imageries du Vivant), supported by France Life Imaging (grant ANR-11-INBS-0006) and Infrastructures Biologie-Santé.

Funding

The authors state that this work has not received any funding.

Author information

Authors and Affiliations

  1. EA FETUS and LUMIERE PLATEFORM – Faculte Paris Descartes, Paris, France

    Naziha Khen-Dunlop, Anne-Elodie Millischer, Nathalie Siauve & Laurent J Salomon

  2. Laboratoire de Recherche en Imagerie (LRI), INSERM U970, Equipe 2, Paris Cardiovascular Research Center - PARCC, 56 Rue Leblanc, 75015, Paris, France

    Naziha Khen-Dunlop, Gihad Chalouhi, Augustin Lecler, Afef Bouchouicha, Bertrand Tavitian, Nathalie Siauve & Daniel Balvay

  3. Department of Pediatric Surgery, Necker-Enfants Malades Hospital, 149 Rue de Sevres, 75105, Paris, France

    Naziha Khen-Dunlop

  4. Department of Pediatric Radiology, Necker-Enfants Malades Hospital, Paris, France

    Anne-Elodie Millischer

  5. Department of Radiology, Georges Pompidou European Hospital, Paris Descartes Medical University, Paris, France

    Bertrand Tavitian

  6. Department of Radiology, Louis Mourier Hospital, Colombes, France

    Nathalie Siauve

  7. Department of Obstetrics, Necker-Enfants Malades Hospital, Paris, France

    Laurent J Salomon

Authors
  1. Naziha Khen-Dunlop
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gihad Chalouhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Augustin Lecler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Afef Bouchouicha
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anne-Elodie Millischer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bertrand Tavitian
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nathalie Siauve
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Daniel Balvay
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Laurent J Salomon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Naziha Khen-Dunlop.

Ethics declarations

Guarantor

The scientific guarantor of this publication is Bertand Tavitian, head of the department.

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

One of the authors has significant statistical expertise (Dr. Afef Bouchouicha).

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Written informed consent was waived by the Institutional Review Board.

Ethical approval

Institutional Review Board approval was obtained.

Methodology

• prospective case- observational

• performed at one institution

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khen-Dunlop, N., Chalouhi, G., Lecler, A. et al. Assessment of BOLD response in the fetal lung. Eur Radiol 31, 3090–3097 (2021). https://doi.org/10.1007/s00330-020-07272-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-020-07272-z

Keywords

Search

Navigation