CEUS Evaluation of Hydrocephalus in Neonates and Infants

Contrast-enhanced ultrasound (CEUS) is a clinically used imaging technique that uses gas-filled microbubbles to enhance the visualization of blood vessels. Ultrasound contrast agents have been approved for use in Europe for around two decades, and in the United States, the FDA has approved the use of Lumason, a second-generation lipid/sulfur hexafluoride ultrasound contrast agent, for the evaluation of focal hepatic lesions, opacification of the left ventricular chamber of the heart and assessment of vesicoureteral reflux in pediatric patients. Unlike computed tomography or magnetic resonance imaging (MRI) contrast agents, ultrasound contrast agents have no associated renal toxicity and do not require ionizing radiation or sedation. The risk of adverse events is the lowest of all contrast agents available, with only minor adverse events reported in children, such as altered taste, tinnitus, light-headedness, and nausea. Previous investigation on cerebral physiology in hydrocephalus has shown that increasing ventricular dilation results in reduced cerebral blood flow, as well as reduced cerebral oxygen saturation and higher oxygen extraction. These findings have been studied with currently available tools such as transcranial Doppler, MRI, and near infrared spectroscopy (NIRS). However, there is no standardized tool for robust assessment of brain health in neonatal hydrocephalus. In this regard, prior work by the study team has shown a promising brain CEUS biomarker of ICP and brain ischemia in the porcine neonatal hydrocephalus model. Specifically, cerebral microvascular flows as measured using brain CEUS correlated with invasively measured ICP and brain ischemia. Therefore, there is a dire need to introduce better imaging tools such as CEUS to the clinical setting that can detect changes in ICP and brain ischemia in patients with hydrocephalus at an early stage and prompt therapeutic implementation/monitoring. The study seeks to validate first the safety and feasibility of performing brain CEUS in neonatal hydrocephalus. Injection of Lumason contrast agent will be performed via the existing peripheral intravenous line or central line using the FDA-recommended dose of up to 0.03 mg/kg. Contrast-agent injection will be performed twice per CEUS scan to ensure image quality and test reproducibility. Two bolus injections will performed to evaluate for dynamic brain perfusion and several 2-minute cine clips as well as static images will be acquired during the exam. Baseline and demographic characteristics will be summarized by standard descriptive statistics. Qualitative analysis will be performed by visual rating by 2 teams, blinded to clinical information, consisting of primary investigator and second radiologist (co-investigator). Each scan will be rated for diagnostic quality and qualitative rating of cranial perfusion. Quantitative analysis will be performed using time-intensity based analysis and the particle image and/or tracking velocimetry (PIV/PTV) method. These calculations will be performed after transferring the DICOM data obtained during the research procedure. The purpose is to utilize post-processing techniques available to the study team.