Brain PERfusion Evaluation by Contrast-Enhanced UltraSound (PerCEUS)

Quantification of Cerebral Perfusion at the Patient's Bedside When Performing Contrast-enhanced Ultrasound in Neurointensive Care Patients

The objective of the study is to assess brain tissue perfusion by contrast-enhanced ultrasound perfusion imaging (PerCEUS) in acute brain injuries. More precisely, it aims :

• to evaluate the heterogeneity of brain perfusion and thus diagnose brain tissue hypoperfusion with contrast-enhanced ultrasound.
• to correlate contrast-enhanced ultrasound with perfusion measurements by usual multimodal monitoring.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke; Subarachnoid Hemorrhage; Cerebral Hemorrhage; Cerebrovascular Circulation; Perfusion
• Intervention / Treatment: Diagnostic test: Measuring contrast-enhanced ultrasound perfusion with phase inversion harmonic imaging

Detailed Description

The main aim is to evaluate the heterogeneity of brain perfusion, thus diagnosing brain tissue hypoperfusion with PerCEUS, then to correlate it with the usual multimodal monitoring.

Earlier after hospitalization in neurointensive care, when the study physician needs to realize a contrast ultrasound imaging and without delaying any emergency procedure, a PerCEUS will be performed in patients with an acute brain injury. After acquisition, data from PerCEUS will be transferred to an external evaluation unit and analysed offline, using commercially available software Qlab (Philips ®). According to the localization of acute brain injuries with magnetic resonance imaging (MRI) and/or computed tomography (CT), several regions-of-interest (ROI, at least three in each area) will be chosen :

• Area 1 : in the core of the lesion (supposed non perfused)
• Area 2 : just next to the lesion (supposed hypoperfused)
• Area 3 : in the saner hemisphere, symmetrically to area 2 each time it's possible (supposed well-perfused).

Every parameters of multimodal monitoring used at the moment of PerCEUS will be relieved :

• intracranial pressure (ICP), cerebral perfusion pressure (CPP), mean arterial pressure (MAP)
• mean flow velocity (MFV) by transcranial doppler (TCD)
• regional cerebral oxygen saturation (rSO2) by Near infrared spectroscopy (NIRS)
• jugular venous oximetry (SjvO2).

The actual PerCEUS measurement takes place at the bedside, is performed by the study physician, and takes about 5 minutes.

The trial duration per patient is 30 minutes, ending after 25 minutes of oversight

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Romain BARTHELEMY, MD; Phone Number: +33 (0)1 49 95 85 15; Email: romain.barthelemy@aphp.fr
• Study Contact Backup: Name: Benjamin Glenn CHOUSTERMAN, MD PhD; Phone Number: +33 (0)1 49 95 85 18; Email: benjamin.chousterman@aphp.fr

Study Locations

• France
  • Paris, France, 75010
    • Recruiting
    • Lariboisiere Hospital
    • Contact: Romain BARTHELEMY, MD; Phone Number: +33149958515; Email: romain.barthelemy@aphp.fr
    • Contact: Benjamin Glenn CHOUSTERMAN, MD PhD; Phone Number: +33149958518; Email: benjamin.chousterman@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients hospitalized in neurosurgical intensive care in Lariboisière Hospital, Paris, with acute brain injuries

Description

Inclusion Criteria:

• Age ≥18
• Intensive care unit admission for acute brain injury
• Proven acute brain injury by CT and/or MRI
• Requiring a contrast ultrasound imaging
• Informed consent of patient or relative

Exclusion Criteria:

• Pregnancy
• Not sufficient temporal window
• Contraindications to Sonovue ® : acute coronary syndromes, severe ischemic heart disease (requiring revascularization), pulmonary arterial hypertension > 90 mmHg, right-left shunt, ARDS, dobutamine's use, known allergy or adverse reaction to Sonovue®
• Patient on State Medical Assistance

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients with acute brain injuries when a contrast ultrasound imaging is requested by the physician; Contrast-enhanced ultrasound perfusion imaging (PerCEUS)

Diagnostic test: Measuring contrast-enhanced ultrasound perfusion with phase inversion harmonic imaging; Contrast-enhanced ultrasound perfusion imaging (PerCEUS) will be performed by a dedicated study team. The transcranial color duplex sonography will be performed with a 1-5 MHz dynamic sector array (S5-1) from a Philips Epiq 7 ultrasound machine (Philips Healthcare, Andover, MA). The field-of-view will be set to an imaging depth of 150 mm in a sector angle of 90°. The imaging plane will be then tilted to the diencephalic, in which the frontal horns of the side ventricles and the third ventricle serve as landmarks and where the anterior and posterior middle cerebral artery (MCA) territory and the basal ganglia (BG) as region of interest could be identified without artefacts from major vessels. High mechanical index bolus imaging will be performed from the sanest side of the head. Data acquisition of 45 seconds will be recorded immediately after the beginning of the contrast ultrasound imaging, using a mechanical index (MI) setting of 1.1 and a frame rate of 33 Hz.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the heterogeneity of brain perfusion by time-to-peak (TPI) measurement	Comparison between time-to-peak (TPI) intensities measured in ROIs in each area by PerCEUS	30 minutes after PerCEUS
Evaluation of the heterogeneity of brain perfusion by peak-intensities (PI) measurement	Comparison between peak-intensities (PI) measured in ROIs in each area by PerCEUS	30 minutes after PerCEUS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between PerCEUS parameters and cerebral perfusion as assessed by ICP and MAP	Correlations test between TPI/PI and ICP/CPP/MAP	30 minutes after PerCEUS
Correlation between PerCEUS parameters and cerebral perfusion as assessed by TCD	Correlations test between TPI/PI and MFV	30 minutes after PerCEUS
Correlation between PerCEUS parameters and cerebral perfusion as assessed by NIRS	orrelations test between TPI/PI and rSO2	30 minutes after PerCEUS
Correlation between PerCEUS parameters and cerebral perfusion as assessed by SjvO2	Correlations test between TPI/PI and SjvO2	30 minutes after PerCEUS

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Romain BARTHELEMY, MD, AP-HP Lariboisière Hospital, Department of Anaesthesia and Intensive Care

Publications and helpful links

General Publications

• Eyding J, Krogias C, Wilkening W, Postert T. Detection of cerebral perfusion abnormalities in acute stroke using phase inversion harmonic imaging (PIHI): preliminary results. J Neurol Neurosurg Psychiatry. 2004 Jun;75(6):926-9. doi: 10.1136/jnnp.2003.026195.
• Eyding J, Fung C, Niesen WD, Krogias C. Twenty Years of Cerebral Ultrasound Perfusion Imaging-Is the Best yet to Come? J Clin Med. 2020 Mar 17;9(3):816. doi: 10.3390/jcm9030816.
• Vinke EJ, Kortenbout AJ, Eyding J, Slump CH, van der Hoeven JG, de Korte CL, Hoedemaekers CWE. Potential of Contrast-Enhanced Ultrasound as a Bedside Monitoring Technique in Cerebral Perfusion: a Systematic Review. Ultrasound Med Biol. 2017 Dec;43(12):2751-2757. doi: 10.1016/j.ultrasmedbio.2017.08.935. Epub 2017 Sep 28.
• Fung C, Heiland DH, Reitmeir R, Niesen WD, Raabe A, Eyding J, Schnell O, Rolz R, Z Graggen WJ, Beck J. Ultrasound Perfusion Imaging for the Detection of Cerebral Hypoperfusion After Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care. 2022 Aug;37(1):149-159. doi: 10.1007/s12028-022-01460-z. Epub 2022 Feb 24.
• Bilotta F, Robba C, Santoro A, Delfini R, Rosa G, Agati L. Contrast-Enhanced Ultrasound Imaging in Detection of Changes in Cerebral Perfusion. Ultrasound Med Biol. 2016 Nov;42(11):2708-2716. doi: 10.1016/j.ultrasmedbio.2016.06.007. Epub 2016 Jul 27.

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: May 29, 2023
• First Submitted That Met QC Criteria: May 29, 2023
• First Posted (Actual): June 7, 2023

Study Record Updates

• Last Update Posted (Actual): June 19, 2025
• Last Update Submitted That Met QC Criteria: June 16, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Diagnostic imaging; Ultrasound perfusion imaging; Brain perfusion; Cerebral blood flow; Transcranial Doppler; Doppler ultrasound; Contrast-enhanced ultrasonography; Contrast enhanced ultrasound; Neurocritical care; Contrast ultrasound; Intracerebral hematoma; Ultrasonography Doppler; Ultrasound contrast agent; Intra-cranial pressure
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Intracranial Hemorrhages; Stroke; Ischemic Stroke; Hemorrhage; Cerebral Hemorrhage; Subarachnoid Hemorrhage
• Other Study ID Numbers: APHP230489; 2023-A00939-36 (Other Identifier: IDRCB number)

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
• product manufactured in and exported from the U.S.: No