Novel Contrast‐Enhanced Ultrasound Evaluation in Neonatal Hypoxic Ischemic Injury: Clinical Application and Future Directions

Abstract

Sensitive, specific, and safe bedside evaluation of brain perfusion is key to the early diagnosis, treatment, and improved survival of neonates with hypoxic ischemic injury. Contrast-enhanced ultrasound (US) imaging is a novel imaging technique in which intravenously injected gas-filled microbubbles generate enhanced US echoes from an acoustic impedance mismatch. This article describes contrast-enhanced US imaging in 2 neonates with hypoxic ischemic injury and future directions on developing quantitative contrast-enhanced US techniques for improved characterization of perfusion abnormalities. The importance of studying the temporal evolution of brain perfusion in neonatal hypoxic ischemic injury is also highlighted.

Contrast‐Enhanced Ultrasound and Elastography Imaging of the Neonatal Brain: A Review

“…When a region of interest is placed a time‐intensity curve is generated allowing for the calculation of the wash‐in (time from injection to peak intensity of contrast), peak intensity (maximum value of contrast on the time‐intensity curve), half washout (time between peak intensity and time when half the enhancement has disappeared), and washout (the time from peak enhancement to when enhancement has completely disappeared) can be calculated (Fig ). The area under the curve is calculated from the beginning of contrast enhancement to the end of washout that can be thought of as a surrogate for perfusion within that region of interest (Fig ) . Two quantitative methods are being developed by our group to rapidly and accurately detect perfusion abnormalities: 1) drawing regions of interest in gray versus the white matter to detect ratio of perfusion changes, in cases of diffuse white matter ischemia 2) generating a microbubble velocity mapping technique to detect regions of ischemia (unpublished data).…”

“…Two quantitative methods are being developed by our group to rapidly and accurately detect perfusion abnormalities: 1) drawing regions of interest in gray versus the white matter to detect ratio of perfusion changes, in cases of diffuse white matter ischemia 2) generating a microbubble velocity mapping technique to detect regions of ischemia (unpublished data). With both qualitative and quantitative data, we believe that cranial CEUS can detect subtle ischemic injuries that cannot be detected with noncontrast cranial United States that correlate well with gold standard MRI . At our institution, we started applying TCEUS for the evaluation of neonatal hypoxic ischemic injury.…”

“…At our institution, we started applying TCEUS for the evaluation of neonatal hypoxic ischemic injury. Using both qualitative and quantitative parameters, we have been able to characterize global perfusion abnormalities in neonates with different etiologies of hypoxic ischemic injury (Fig ) …”

Advanced Pediatric Neurosonography Techniques: Contrast‐Enhanced Ultrasonography, Elastography, and Beyond

“…This approach transforms US from a primarily, often experience‐based, qualitative imaging tool, toward an objective, reproducible quantitative test. Hwang et al have proposed utilizing gray versus white matter perfusion ratios for detection of diffuse, symmetric injuries . As a novel quantification tool, Hwang's research team has also applied microbubble velocity mapping to the brain, which is based on the mapping of velocity and trajectory of individual microbubble across multiple time frames.…”

Head Ultrasound in Neonatal Hypoxic-Ischemic Injury and Its Mimickers for Clinicians: A Review of the Patterns of Injury and the Evolution of Findings Over Time

“…The technique permits real-time quantification of tissue perfusion, specifically via generation of perfusion kinetics curves from which perfusion parameters including wash-in, time to peak, peak intensity, and area under the curve can be derived. The application of the contrast-enhanced US technique is in the preliminary stages due to off-label use in the neonatal brain, but it is showing promise based on the initial case series on neonatal HII [86]. Dynamic color Doppler sonography permits perfusion quantification of a region of interest without intravenous contrast.…”