Contrast‐Enhanced Ultrasound in Extracorporeal Support: In Vitro Studies and Initial Experience and Safety Data in the Extreme Premature Fetal Lamb Maintained by the Extrauterine Environment for Neonatal Development

Abstract

Objectives To evaluate the effects of ultrasound contrast agent (UCA) administration on hemodynamic parameters and support equipment in in vitro and in vivo models of extracorporeal support. Methods In vitro, incrementally increasing bolus doses of a UCA were administered proximal to a membrane oxygenator, and ultrasound cine clips were obtained. The rates of microbubble destruction across the oxygenator and over time were calculated from time‐intensity‐curves. Measurements across the membrane oxygenator were recorded and compared by a repeated‐measures analysis of variance. In vivo, 7 premature fetal lambs were transferred from placental support to the extrauterine environment for neonatal development. Contrast agent boluses were administered for contrast‐enhanced ultrasound (CEUS) examinations. Hemodynamic parameters and serum laboratory values were evaluated before and after the examinations by paired t tests. For oxygenator staining, oxygenator membranes from the in vitro circuit, study animals (n = 4), and control animals (n = 4) were stained for the adherent UCA. Results In vitro, with all doses (0.1–4 mL), there was no difference in measured parameters across the oxygenator (P ≥ .09). Contrast agent destruction (3%–14%) across the oxygenator was observed at the first pass with a progressive decline in contrast intensity over time. In vivo, there was no difference in hemodynamic parameters or serum laboratory values (P ≥ .08) with any CEUS examination (n = 17). For oxygenator staining, all oxygenator membranes were negative for UCA with lipid staining. Conclusions The UCA had no detectable effect on the oxygenator or measured parameters in in vitro and in vivo studies, thus providing additional safety data to support the use of CEUS in the setting of extracorporeal support.

Contrast‐enhanced ultrasound imaging can be used to evaluate fetal cerebral perfusion: potential implications for fetal surgery

“…Ewes were anesthetized with intramuscular ketamine (15 mg/kg) and inhaled isoflurane (1-4 % in O 2 ) and positioned in left lateral decubitus. Ventilator tidal volume (8-10 ml/kg/min) and respiratory rate (10)(11)(12)(13)(14)(15)(16)(17)(18) were adjusted to achieve a maternal end-tidal CO 2 of 35-40mm Hg and arterial CO 2 of 35-45 mm Hg.…”

“…Lumason® (sulfur hexafluoride lipid-type A microspheres; Bracco Diagnostics Inc., Monroe Township, NJ, USA) ultrasound contrast agent was administered as a bolus via the fetal umbilical vein (ex utero, 0.2mL) or via fetal arterial catheter (in utero, 0.3mL) with simultaneous ultrasound cine acquisition. Previous literature has documented CEUS safety data in the EXTEND model [17]. Ninety-second cine clips were obtained of the brain in a transaxial (ex utero) or coronal (in utero) plane which included the thalami (Figs.…”

Contrast-enhanced Ultrasound Imaging Can be Used to Evaluate Fetal Cerebral Perfusion: Potential Implications for Fetal Surgery

“…15 Ewes were anesthetized with intramuscular ketamine (15 mg/kg) and inhaled iso urane (1-4% in O 2 ) and positioned in left lateral decubitus. Ventilator tidal volume (8-10 ml/kg/min) and respiratory rate (10)(11)(12)(13)(14)(15)(16)(17)(18) were adjusted to achieve a maternal end-tidal CO 2 of 35-40 mm Hg and arterial CO 2 of 35-45 mm Hg.…”

“…Previous literature has documented CEUS safety data in the EXTEND model. 17 Ninety-second cine clips were obtained of the brain in a transaxial (ex utero) or coronal (in utero) plane which included the thalami ( Fig. 2A).…”

Contrast‐Enhanced Brain Ultrasound Perfusion Metrics in the EXTra‐Uterine Environment for Neonatal Development (EXTEND): Correlation With Hemodynamic Parameters

“…[9][10][11] We have previously shown that CEUS can be used safely to evaluate brain perfusion metrics in this model. 12 Using this preclinical ovine model, our objective was to determine the association between fetal hemodynamics and concurrently measured CEUS perfusion parameters to attain greater understanding of the applications of these quantitative techniques.…”