Preterm Neonates Brain Ultrasound With CEUS and Elastography

The aim of the study is to investigate levels of brain perfusion and elasticity in preterm neonates when they reach the estimated due date and to compare the data with magnetic resonance imaging at term. Contrast enhanced ultrasound (sulphur hexafluoride) and ultrasound-assisted elastography will be used to evaluate the state of brain perfusion with ultrasound. Different appropriate imaging sequences will be used regarding MRI, including asl-perfusion. Neonates recruited from the Neonatal Intensive Care Unit (NICU) of Turku University Hospital will be recruited.

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 this study is to examine cerebral hemodynamics in preterm neonates reaching term age, using ultrasound of the brain, contrast enhanced ultrasound (CEUS) and ultrasound-guided shear-wave elastography (US-SWE). The brain ultrasound, CEUS and US-SWE to preterm babies is planned to take place while having a clinically appointed brain magnetic resonance imaging at about term. Total recruitment for the study is 100 infants in total. The recruitment period will be up to seven years if needed. The injections of SonoVue will be administered through pre-existing venous cannulas. The examination will be done in addition to the MR-imaging, after 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. 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. Ultrasound data will be evaluated comparing preterm neonates with and without MRI-proven brain pathology and comparing the ultrasound-achieved data to magnetic resonance imaging.

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 at term in infants born prematurely Other Names: • SonoVue

To study brain perfusion with brain ultrasound, contrast enhanced ultrasound of the brain and ultrasound-guided shear-wave elastography

To evaluate the differences in brain perfusion and elasticity studied by CEUS and shear-wave elastography, comparing term neonates with and without MRI verified brain pathologies and to compare the ultrasound CEUS and elastography data to MRI.

Quantitative assessment of neonatal brain perfusion using calculated time-intensity curve of enhancement in brain CEUS at term

Quantitative analysis will be executed from a time-intensity curve generated from a region of interest and from left and right talami. Wash-in slope and wash-out slope (measured in echo power units per second) will be measured and compared on healthy versus diseased preterm neonates at term.

Quantitative assessment of neonatal brain peak enhancement using calculated time-intensity curve of enhancement in brain CEUS at term

Quantitative analysis will be executed from a time-intensity curve generated from a region of interest and from left and right talami. Peak enhancement will be measured as maximum echo power on time-intensity curve.

Quantitative assessment of neonatal brain perfusion time to peak using calculated time-intensity curve of enhancement in brain CEUS at term

Quantitative analysis will be executed from a time-intensity curve generated from a region of interest and from left and right talami. Time to peak will be measured in seconds in time-intensity curve.

Quantitative assessment of neonatal brain perfusion volume using calculated time-intensity curve of enhancement in brain CEUS at term

Quantitative analysis will be executed from a time-intensity curve generated from a region of interest and from left and right talami. Area under the curve reporting total enhancement volume from time-intensity curve.

Neonatal brain perfusion assessed with time-intensity curves of contrast enhanced ultrasound compared with brain magnetic resonance asl perfusion imaging

Time-intensity curves of CEUS and MRI ASL-perfusion studies will be performed comparing time to peak, peak enhancement, wash-in and wash-out curves and mean transit times on different imaging methods. Assessment will be done in correlation with clinical information.

Quantitative analysis of repeated US-SWE measurements on both hemispheres of thalami and areas of interest estimated by brain ultrasound and elastography. Tissue elasticity will be reported in kilopascals, comparing the findings of thalami and regions of interest on the left and on the right.

Inclusion Criteria: Preterm neonates attending brain MR-imaging at term 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