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

Quantifizierung Der Hirnperfusion Während Kinderherzchirurgischer Operationen Durch Transkraniellen Kontrastmittelverstärkten Ultraschall

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.

Study Overview

• Status: Completed
• Conditions: Heart Defects, Congenital
• Intervention / Treatment: Diagnostic test: TCEUS

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Erlangen, Germany, 91054
    • University Hospital of Erlangen-Nürnberg, Department of Pediatric Cardiac Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 4 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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

3

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University of Erlangen-Nürnberg Medical School
• Investigators: Principal Investigator: André Rüffer, MD, University Hospital Erlangen, Department of Pediatric Cardiac Surgery; Principal Investigator: Jörg Jüngert, MD, University Hospital Erlangen, Department of Pediatrics

Publications and helpful links

General Publications

• Knieling F, Cesnjevar R, Regensburger AP, Wagner AL, Purbojo A, Dittrich S, Munch F, Neubert A, Woelfle J, Jungert J, Ruffer A. Transfontanellar Contrast-enhanced US for Intraoperative Imaging of Cerebral Perfusion during Neonatal Arterial Switch Operation. Radiology. 2022 Jul;304(1):164-173. doi: 10.1148/radiol.212044. Epub 2022 Apr 5.
• Ruffer A, Knieling F, Cesnjevar R, Regensburger A, Purbojo A, Dittrich S, Munch F, Wolfle J, Jungert J. Equal cerebral perfusion during extended aortic coarctation repair. Eur J Cardiothorac Surg. 2022 Jan 24;61(2):299-306. doi: 10.1093/ejcts/ezab415.

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2017
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): August 30, 2021

Study Registration Dates

• First Submitted: July 4, 2017
• First Submitted That Met QC Criteria: July 10, 2017
• First Posted (Actual): July 12, 2017

Study Record Updates

• Last Update Posted (Actual): September 29, 2021
• Last Update Submitted That Met QC Criteria: September 28, 2021
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: contrast enhanced ultrasound; perfusion; CEUS; SonoVue; cerebral perfusion; TCEUS; sulphur hexafluoride
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Cardiovascular Abnormalities; Congenital Abnormalities; Heart Defects, Congenital
• Other Study ID Numbers: 20_17B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No