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Quantitative contrast-enhanced ultrasound of the brain on twin fetal lambs maintained by the extrauterine environment for neonatal development (EXTEND): initial experience

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Abstract

Background

With the development of an artificial environment to support the extremely premature infant, advanced imaging techniques tested in this extrauterine system might be beneficial to evaluate the fetal brain.

Objective

We evaluated the feasibility of (a) performing contrast-enhanced ultrasound (CEUS) and (b) quantifying normal and decreased brain perfusion in fetal lambs maintained on the extrauterine environment for neonatal development (EXTEND) system.

Materials and methods

Twin premature fetal lambs (102 days of gestational age) were transferred to the EXTEND system. Twin B was subjected to sub-physiological flows (152 mL/kg/min) and oxygen delivery (15.9 mL/kg/min), while Twin A was maintained at physiological levels. We administered Lumason contrast agent into the oxygenator circuit and performed serial CEUS examinations. We quantified perfusion parameters and generated parametric maps. We also recorded hemodynamic parameters, serum blood analysis, and measurements across the oxygenator. Postmortem MRIs were performed.

Results

No significant changes in hemodynamic variables were attributable to CEUS examinations. On gray-scale images, Twin B demonstrated ventriculomegaly and progressive parenchymal volume loss culminating in hydranencephaly. By CEUS, Twin B demonstrated decreased peak enhancement and decreased overall parenchymal perfusion when compared to Twin A by perfusion parameters and parametric maps. Changes in perfusion parameters were detected immediately following blood transfusion. Postmortem MRI confirmed ultrasonographic findings in Twin B.

Conclusion

In this preliminary experience, we show that CEUS of the brain is feasible in fetal lambs maintained on the EXTEND system and that changes in perfusion can be quantified, which is promising for the application of CEUS in this extrauterine system supporting the premature infant.

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Acknowledgments

Preliminary results were presented at the Society for Pediatric Radiology annual meeting May 18, 2018, in Nashville, TN.

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Authors and Affiliations

  1. Department of Radiology, The Children’s Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA, 19104, USA

    Anush Sridharan, Juan S. Martin-Saavedra & Ryne A. Didier

  2. Department of Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Kendall M. Lawrence, Marcus G. Davey & Alan W. Flake

  3. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Alan W. Flake & Ryne A. Didier

Authors
  1. Anush Sridharan
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  2. Kendall M. Lawrence
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  3. Juan S. Martin-Saavedra
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  4. Marcus G. Davey
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  5. Alan W. Flake
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  6. Ryne A. Didier
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Corresponding author

Correspondence to Ryne A. Didier.

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Conflicts of interest

Dr. Marcus Davey and Dr. Alan Flake are patent holders on the described extrauterine support device. The authors report no financial conflicts of interest pertaining to the data reported in this manuscript.

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Supplementary Material 1

Contrast-enhanced US (CEUS) examination in Twin A. Cine clip in a transcranial coronal view using dual-mode imaging with gray-scale US (left) and CEUS (right) images following intravenous contrast administration. Wash-in perfusion of the brain up to peak enhancement in Twin A at gestational age 105 days (AVI 8136 kb)

Supplementary Material 2

Contrast-enhanced US (CEUS) examination in Twin B. Cine clip in a transcranial coronal view using dual-mode imaging with gray-scale US (left) and CEUS (right) images following intravenous contrast administration. Wash-in perfusion of the brain up to peak enhancement in Twin B at gestational age 108 days (AVI 15226 kb)

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Sridharan, A., Lawrence, K.M., Martin-Saavedra, J.S. et al. Quantitative contrast-enhanced ultrasound of the brain on twin fetal lambs maintained by the extrauterine environment for neonatal development (EXTEND): initial experience. Pediatr Radiol 51, 103–111 (2021). https://doi.org/10.1007/s00247-020-04797-9

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  • DOI: https://doi.org/10.1007/s00247-020-04797-9

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