Neonatal Brain Ultrasound With CEUS and Elastography

Contrast Enhanced Ultrasound and Elastography of the Neonatal Brain

The aim of our study is to investigate changes of brain perfusion and elasticity in neonates during the time that a neonate is adapting to live outside the womb and during diseases that are suspected to affect neonatal brain perfusion. We use contrast enhanced ultrasound (sulphur hexafluoride) and ultrasound-assisted elastography to evaluate the state of brain perfusion. We will study neonates recruited from the Neonatal Units of Turku University Hospital.

Study Overview

• Status: Not yet recruiting
• Conditions: Neonatal Stroke; Neonatal Hypoxic Ischemic Encephalopathy; Neonatal Encephalopathy, Unspecified
• Intervention / Treatment: Diagnostic test: Brain contrast enhanced ultrasound, brain ultrasound elastography; Drug: Sulfur Hexafluoride

Detailed Description

SonoVue (sulphur hexafluoride) is a contrast agent composed of micro bubbles. It increases echogenicity of the ultrasound thus enhancing the visualisation of vessels and giving better insights into tissue perfusion. The use of sulphur hexafluoride has been approved by FDA and it has been in off-label use in Europe for years. SonoVue is thought to be especially useful for children, because it can enhance the diagnostic capabilities of ultrasound and the examination can be performed without radiation or sedation.

Elastography is a method to investigate the elasticity of a tissue by tracking the shear waves generated by the ultrasound beam. Also this method has been used in Europe and America for years.

The aim of our study is to examine cerebral hemodynamics in neonates using ultrasound of the brain, contrast enhanced ultrasound (CEUS) and ultrasound-guided shear-wave elastography (US-SWE). We aim to recruit four groups of infants: those with no suspected diseases affecting brain perfusion on the first days after birth and infants with either asphyctic injury, stroke or other diseases affecting central nervous system. Total recruitment for different groups is 100 infants in total, during this first study phase. The recruitment period will be up to seven years if needed.

The injections of SonoVue will be administered through pre-existing venous cannulas. The first examination after brain injury will be done as soon as the parental consent has been given. The ultrasound examination altogether is estimated to take about 20 minutes per day. Safety monitoring period is conducted after the injection. The studies will be repeated 0-4 times according to the approval of the caretakers of the child and the disease the child is affected by. CEUS data will be analysed with proper software. US-SWE will be measured repeatedly on both brain hemispheres and on different areas to validate the measurements.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Tiina Laurikainen; Phone Number: +35823135941; Email: tiina.laurikainen@tyks.fi
• Study Contact Backup: Name: Riitta Parkkola; Phone Number: +35823130148; Email: riitta.parkkola@tyks.fi

Study Locations

• Finland
  • Southwestern Finland
    • Turku, Southwestern Finland, Finland, 20520
      • Turku University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 10 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Babies less than 7 months treated at the neonatal units of Turku University hospital

Exclusion Criteria:

• Pre-known genetic disease
• Difficult congenital malformations that need surgical treatment
• Central nervous system tumors
• Weight less than 2,5 kg during examination
• Medical history of SonoVue hypersensitivity
• Uncontrolled systemic hypertension
• Systolic pulmonary artery pressure > 90 mmHg
• Unstable cardiovascular state

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Term neonates; Diagnostic Test: Brain ultrasound, brain contrast enhanced ultrasound, brain ultrasound elastography, cardiac ultrasound To study brain perfusion with brain ultrasound, contrast enhanced ultrasound of the brain and ultrasound-guided shear-wave elastography Drug: Sulfur Hexafluoride To evaluate brain perfusion in infants with no suspected brain pathology using CEUS. Later, different patient groups could be compared to infants with no suspected brain pathology. Other Names: • SonoVue	Diagnostic test: Brain contrast enhanced ultrasound, brain ultrasound elastography; To study brain perfusion with brain ultrasound, contrast enhanced ultrasound of the brain and ultrasound-guided shear-wave elastography; Drug: Sulfur Hexafluoride; To evaluate the differences in brain perfusion studied by CEUS, comparing different patient groups and babies with no suspected brain pathology; Other Names: SonoVue
Experimental: Neonatal asphyxia; Diagnostic Test: Brain ultrasound, brain contrast enhanced ultrasound, brain ultrasound elastography To study brain perfusion with brain ultrasound, contrast enhanced ultrasound of the brain and ultrasound-guided shear-wave elastography Drug: Sulfur Hexafluoride To evaluate brain perfusion in neonates after birth asphyxia Other Names: • SonoVue	Diagnostic test: Brain contrast enhanced ultrasound, brain ultrasound elastography; To study brain perfusion with brain ultrasound, contrast enhanced ultrasound of the brain and ultrasound-guided shear-wave elastography; Drug: Sulfur Hexafluoride; To evaluate the differences in brain perfusion studied by CEUS, comparing different patient groups and babies with no suspected brain pathology; Other Names: SonoVue
Experimental: Neonatal stroke; Diagnostic Test: Brain contrast enhanced ultrasound, brain ultrasound elastography To study brain perfusion with brain ultrasound, contrast enhanced ultrasound of the brain and ultrasound-guided shear-wave elastography Drug: Sulfur Hexafluoride To evaluate brain perfusion after neonatal stroke Other Names: • SonoVue	Diagnostic test: Brain contrast enhanced ultrasound, brain ultrasound elastography; To study brain perfusion with brain ultrasound, contrast enhanced ultrasound of the brain and ultrasound-guided shear-wave elastography; Drug: Sulfur Hexafluoride; To evaluate the differences in brain perfusion studied by CEUS, comparing different patient groups and babies with no suspected brain pathology; Other Names: SonoVue
Experimental: Other neonatal brain pathologies; Diagnostic Test: Brain ultrasound, brain contrast enhanced ultrasound, brain ultrasound elastography To study brain perfusion with brain ultrasound, contrast enhanced ultrasound of the brain and ultrasound-guided shear-wave elastography Drug: Sulfur Hexafluoride To evaluate brain perfusion in infants with other type (no asphyxia, stroke or preterm birth related) of brain pathology, like hydrocephalus, hemorrhage or central nervous system infection Other Names: • SonoVue	Diagnostic test: Brain contrast enhanced ultrasound, brain ultrasound elastography; To study brain perfusion with brain ultrasound, contrast enhanced ultrasound of the brain and ultrasound-guided shear-wave elastography; Drug: Sulfur Hexafluoride; To evaluate the differences in brain perfusion studied by CEUS, comparing different patient groups and babies with no suspected brain pathology; Other Names: SonoVue

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Repeated qualitative and quantitative assessment of neonatal brain perfusion using contrast-enhanced ultrasound of the brain	Visual assessment of contrast enhancement on both brain hemispheres. Quantitative analysis of proper ultrasound parameters, such as wash-in and wash-out curves, during the adaptive period and during different brain pathologies and their treatment.	20 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Repeated qualitative assessment of neonatal brain elasticity using ultrasound-guided shear wave elastography	Quantitative analysis of repeated US-SWE measurements on both hemispheres and areas of interest estimated by brain ultrasound and CEUS	20 days
Comparing the brain perfusion in neonates with no diseases affecting brain perfusion and neonates with different brain pathologies	Quantitative analysis of proper contrast-enhanced ultrasound parameters, such as wash-in and wash-out curves, in neonates with normal brain perfusion compared to neonates with different brain pathologies.	20 days

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Investigators: Principal Investigator: Tiina Laurikainen, Turku University Hospital; Study Director: Riitta Parkkola, Turku University Hospital; Study Chair: Vilhelmiina Parikka, Turku University Hospital; Study Chair: Jussi Hirvonen, Turku University Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2023
• Primary Completion (Anticipated): July 1, 2029
• Study Completion (Anticipated): December 1, 2029

Study Registration Dates

• First Submitted: December 5, 2022
• First Submitted That Met QC Criteria: December 5, 2022
• First Posted (Actual): December 13, 2022

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 24, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Hypoxia; Hypoxia, Brain; Brain Ischemia; Brain Diseases; Hypoxia-Ischemia, Brain
• Other Study ID Numbers: TL16102021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No