Quantification of Cerebral Perfusion by Contrast-enhanced Ultrasound During Neonatal Heart Surgery

Study Overview
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Brief Summary
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Transcranial contrast-enhanced ultrasound for evaluation of cerebral blood flow during pediatric cardiac surgery. This study is aimed as a feasibility study prior to conducting a lager prospective clinical trial including neurologic and developmental outcome measures.

Detailed Description
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The cerebral perfusion of infants with congenital heart defects is a critical determinant during cardiac surgery. The majority of these interventions is performed during deep or moderate hypothermia (25-32°C) with reduced blood flow of the heart-lung-machine (HLM). Assuming a symmetrical anatomy of the cerebral arteries (C. Willisii) a single vessel (T. brachiocephalicus) is then supplying the cerebral blood flow. Using contrast-enhanced ultrasound the cerebral blood flow will be assessed during cardiac surgery interventions.

Official Title
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Quantifizierung Der Hirnperfusion Während Kinderherzchirurgischer Operationen Durch Transkraniellen Kontrastmittelverstärkten Ultraschall

Conditions
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Heart Defects, Congenital

Intervention / Treatment
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* Diagnostic Test: TCEUS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Neonates and infants ≤ 4 month (open fontanelle) Proper ultrasound conditions/window Appropriate general and neurologic state of health Written consent of both parents/guardians Availability of trained sonographer (medical doctor) Exclusion Criteria: Absence of trained sonographer (medical doctor) Intolerance against SonoVue® (bzw. sulphur hexafluoride) Missing signed consent Reduced or inappropriate general and neurologic state of health Preexisting cerebral injury

Ages Eligible for Study
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Maximum Age: 4 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A - TCEUS with HLM<br>General neonatal cardiac surgery with HLM (art. switch, aortopulmonary shunts) | Diagnostic Test: TCEUS<br>* Intravenous sulphur hexafluoride microbubbles<br>* Other names: Transcranial contrast-enhanced ultrasound;|
| Experimental: Group B - TCEUS with HLM<br>Surgery of the aortic arc | Diagnostic Test: TCEUS<br>* Intravenous sulphur hexafluoride microbubbles<br>* Other names: Transcranial contrast-enhanced ultrasound;|
| Active Comparator: Group C - TCEUS without HLM<br>Neonatal cardiac surgery without HLM | Diagnostic Test: TCEUS<br>* Intravenous sulphur hexafluoride microbubbles<br>* Other names: Transcranial contrast-enhanced ultrasound;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-To-Peak (TTP) | Relative/percentage difference of cerebral perfusion by TCEUS-based quantification using VueBox(R) software | Intraoperative (Directly after start of surgical intervention (T1) vs. Directly before end of intervention (T5)) | 
| Mean-Transit-Time (MTT) | Relative/percentage difference of cerebral perfusion by TCEUS-based quantification using VueBox(R) software | Intraoperative (Directly after start of surgical intervention (T1) vs. Directly before end of intervention (T5)) | 
| Maximum Intensity (MI) | Relative/percentage difference of cerebral perfusion by TCEUS-based quantification using VueBox(R) software | Intraoperative (Directly after start of surgical intervention (T1) vs. Directly before end of intervention (T5)) | 
| Relative Blood Volume (RBV) | Relative/percentage difference of cerebral perfusion by TCEUS-based quantification using VueBox(R) software | Intraoperative (Directly after start of surgical intervention (T1) vs. Directly before end of intervention (T5)) | 
| Relative Blood Flow (RBF) | Relative/percentage difference of cerebral perfusion by TCEUS-based quantification using VueBox(R) software | Intraoperative (Directly after start of surgical intervention (T1) vs. Directly before end of intervention (T5)) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-To-Peak (TTP) | Relative/percentage difference of cerebral perfusion by TCEUS-based quantification using VueBox(R) software | Directly after start of surgical intervention (T1) vs. Directly after full flow of HLM at 37°C (T2) | 
| Time-To-Peak (TTP) | Relative/percentage difference of cerebral perfusion by TCEUS-based quantification using VueBox(R) software | Directly after start of surgical intervention (T1) vs. Directly after full flow of HLM at 25-28°C/hypothermia (T3) | 
| Time-To-Peak (TTP) | Relative/percentage difference of cerebral perfusion by TCEUS-based quantification using VueBox(R) software | Directly after start of surgical intervention (T1) vs. Directly after low flow of HLM at 25-28°C/hypothermia (T4) | 
| Mean-Transit-Time (MTT) | Relative/percentage difference of cerebral perfusion by TCEUS-based quantification using VueBox(R) software | Directly after start of surgical intervention (T1) vs. Directly after full flow of HLM at 37°C (T2) | 
| Mean-Transit-Time (MTT) | Relative/percentage difference of cerebral perfusion by TCEUS-based quantification using VueBox(R) software | Directly after start of surgical intervention (T1) vs. Directly after full flow of HLM at 25-28°C/hypothermia (T3) | 
| Mean-Transit-Time (MTT) | Relative/percentage difference of cerebral perfusion by TCEUS-based quantification using VueBox(R) software | Directly after start of surgical intervention (T1) vs. Directly after low flow of HLM at 25-28°C/hypothermia (T4) | 
| Maximum Intensity (MI) | Relative/percentage difference of cerebral perfusion by TCEUS-based quantification using VueBox(R) software | Directly after start of surgical intervention (T1) vs. Directly after full flow of HLM at 37°C (T2) | 
| Maximum Intensity (MI) | Relative/percentage difference of cerebral perfusion by TCEUS-based quantification using VueBox(R) software | Directly after start of surgical intervention (T1) vs. Directly after full flow of HLM at 25-28°C/hypothermia (T3) | 
| Maximum Intensity (MI) | Relative/percentage difference of cerebral perfusion by TCEUS-based quantification using VueBox(R) software | Directly after start of surgical intervention (T1) vs. Directly after low flow of HLM at 25-28°C/hypothermia (T4) | 
| Relative Blood Volume (RBV) | Relative/percentage difference of cerebral perfusion by TCEUS-based quantification using VueBox(R) software | Directly after start of surgical intervention (T1) vs. Directly after full flow of HLM at 37°C (T2) | 
| Relative Blood Volume (RBV) | Relative/percentage difference of cerebral perfusion by TCEUS-based quantification using VueBox(R) software | Directly after start of surgical intervention (T1) vs. Directly after full flow of HLM at 25-28°C/hypothermia (T3) | 
| Relative Blood Volume (RBV) | Relative/percentage difference of cerebral perfusion by TCEUS-based quantification using VueBox(R) software | Directly after start of surgical intervention (T1) vs. Directly after low flow of HLM at 25-28°C/hypothermia (T4) | 
| Relative Blood Flow (RBF) | Relative/percentage difference of cerebral perfusion by TCEUS-based quantification using VueBox(R) software | Directly after start of surgical intervention (T1) vs. Directly after full flow of HLM at 37°C (T2) | 
| Relative Blood Flow (RBF) | Relative/percentage difference of cerebral perfusion by TCEUS-based quantification using VueBox(R) software | Directly after start of surgical intervention (T1) vs. Directly after full flow of HLM at 25-28°C/hypothermia (T3) | 
| Relative Blood Flow (RBF) | Relative/percentage difference of cerebral perfusion by TCEUS-based quantification using VueBox(R) software | Directly after start of surgical intervention (T1) vs. Directly after low flow of HLM at 25-28°C/hypothermia (T4) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CEUS, TCEUS, contrast enhanced ultrasound, perfusion, cerebral perfusion, sulphur hexafluoride, SonoVue