CEUS Evaluation of Hydrocephalus in Neonates and Infants

NCT ID: NCT06693752

Last Updated: 2025-12-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-15
• Study Completion Date: 2027-08-01

Brief Summary

Hydrocephalus affects up to 2 out of every 500 births and results in long-term disability in up to 78% of those affected. The standard treatment of hydrocephalus is cerebrospinal fluid (CSF) diversion via placement of an invasive ventricular shunt to relieve elevated intracranial pressure (ICP). The clinical decision for CSF diversion is based on the ventricular size and clinical symptoms which are not robust indicators of brain health in neonatal hydrocephalus. The purpose of this study is to assess the safety and feasibility of performing brain contrast-enhanced ultrasound (CEUS) in neonates and infants with diagnosed and/or suspected hydrocephalus.

Detailed Description

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.

Conditions

Hydrocephalus in Infants; Hydrocephalus Acquired

Keywords

Ultrasound; Contrast-enhanced ultrasound; Infant hydrocephalus

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Brain contrast-enhanced ultrasound

The study duration per subject will be up to 30 minutes including the time to prepare the contrast agent, perform the pre-contrast imaging and the contrast-enhanced ultrasound (CEUS), as well as the 60-minute monitoring period after the administration of the contrast agent. A second CEUS exam may be performed within 1-2 weeks from the first scan for up to two CEUS exams of 1 hour and 30-minute duration each. Study participation will be complete when the 60-minute monitoring period of the last CEUS performed is complete.

Group Type: EXPERIMENTAL

Sulfur Hexafluoride Lipid Type A Microspheres 25 mg Injection Powder for Suspension [LUMASON]

Intervention Type: DRUG

Injection of Sulfur hexafluoride lipid-type A microspheres contrast agent will be performed via the existing peripheral intravenous line using the FDA-recommended dose of 0.03 mg/kg before performing the contrast-enhanced ultrasound. The weight-based dose of 0.03 mL per kg will be repeated one time during a single examination. Following each injection, an intravenous flush of 0.9% Sodium Chloride is injected.

Interventions

Sulfur Hexafluoride Lipid Type A Microspheres 25 mg Injection Powder for Suspension [LUMASON]

Injection of Sulfur hexafluoride lipid-type A microspheres contrast agent will be performed via the existing peripheral intravenous line using the FDA-recommended dose of 0.03 mg/kg before performing the contrast-enhanced ultrasound. The weight-based dose of 0.03 mL per kg will be repeated one time during a single examination. Following each injection, an intravenous flush of 0.9% Sodium Chloride is injected.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Males and females younger than 1.5 years old with diagnosed and/or suspected hydrocephalus.

2. Post menstrual age of 26 weeks or older.

3. Inpatients at the Children's Hospital of Philadelphia.

4. Parental/Legally authorized representative permission.

Exclusion Criteria

1. Medical history of Lumason hypersensitivity.

2. Hemodynamic instability as defined by rapid escalation of cardiopulmonary support in the past 12-24 hours, as defined by the clinical care team.

3. Respiratory instability as defined by rapid escalation of respiratory support in the past 12-24 hours (Increased fraction of inspired oxygen (FiO2) requirement and/or nitric oxide).

• Minimum Eligible Age: 1 Minute
• Maximum Eligible Age: 18 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital of Philadelphia

OTHER

Sponsor Role: lead

Responsible Party

Misun Hwang, MD

Sponsor Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Misun Hwang, MD

Role: CONTACT

Phone: 267-425-7110

Email: hwangm@chop.edu

Maria Mezher, MD

Role: CONTACT

Phone: 267-425-5821

Email: mezherm@chop.edu

Facility Contacts

Misun Hwang, MD

Role: primary

Maria Mezher, MD

Role: backup

Other Identifiers

24-022232

Identifier Type: -

Identifier Source: org_study_id