Dynamic Contrast-enhanced Ultrasound Imaging for Cerebral Perfusion Measurement in Acute Ischemic Stroke

July 8, 2016 updated by: University Hospital Inselspital, Berne

Stroke, a personal, familial, and social disaster, is the first cause of acquired disability, the second cause of dementia, and the third cause of death worldwide. Its associated socio-economic costs are astronomic. The burden of stroke is likely to increase, given the aging of the population and the growing incidence of many vascular risk factors. Therefore, apart from further development of stroke prevention and treatment strategies, rational and effective tools for diagnosis, monitoring, and follow-up for stroke patients have potential high long-term clinical and economic consequences.

For neuroradiological work-up, computed tomography (CT) or magnetic resonance imaging (MRI) are used as gold standard techniques to detect presence or absence, effective state, and extent of stroke. However, these techniques achieve simply a baseline study of ischemia occurred and can deliver only a snapshot of brain parenchyma and vessels. Furthermore, their rapid and actual availability, especially in primary hospitals, and their dynamic capabilities and predictive values for further infarction are poor with critically ill patients have to be repeatedly transferred to the scanning unit for each measurement. Whereas CT examination is associated with x-ray radiation and may miss early detection of stroke, MRI is associated with higher costs and not generally routinely and around-the clock available in all the hospitals. Therefore, a simple, fast, repeatable, non-hazardous, and non-invasive dynamic bedside tool for the detection of acute brain tissue hypoperfusion and monitoring for potential further infarction or efficacy of thrombolysis either by systemic intravenous thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) or by selective intraarterial fibrinolysis and mechanical recanalization, both combined with or without bridging after acute ischemic stroke, is strongly needed.

A promising alternative method of diagnosing stroke represents contrast-enhanced ultrasound perfusion imaging (UPI). What makes UPI so valuable is the advantage of repeatedly and non-invasively detecting brain tissue at risk for infarction by dynamic direct brain tissue perfusion assessment and not by surrogate parameters, like blood flow velocity or vessel diameter. Because of the possibility to screen and repeatedly measure the state of perfusion, the chances increase to diagnose and monitor ischemic stroke and to define the appropriate window for treatment. The perfusion analysis would also allow determination of treatment results and guidance of rapid and adequate further therapy.

Therefore, the present pilot study in 40 patients is initiated. The objectives of this observational diagnostic cohort trial are to evaluate feasibility and practicability of repeated bedside assessments by contrast enhanced UPI in acute ischemic stroke patients and to assess whether UPI can detect alterations in brain tissue perfusion before and after recanalising therapy of strokes. Assessment of cerebral perfusion by CT or MRI serves as reference and its results are compared to UPI data.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background

Stroke is a personal, familial and social disaster. Apart from development of stroke prevention and treatment strategies, the mainstay of stroke research remains new-product development and improvement of current imaging tools for diagnosis, monitoring and follow-up of stroke patients. For initial neuroradiological work-up, usually computed tomography (CT) or magnetic resonance imaging (MRI) are used to detect presence or absence, effective state and extent of stroke. However, their rapid and actual availability, especially in primary hospitals, and their dynamic capabilities and predictive values for further infarction are poor. Currently cerebral CT-perfusion (CTP) imaging can be regarded as the gold standard for assessing tissue hypoperfusion in this setting. It employs, however, both contrast agent and X-ray exposition and patients have to be repeatedly transferred to the scanning unit for each measurement. Therefore, a fast, simple, repeatable, non-hazardous and non-invasive dynamic bedside tool for the detection of acute brain tissue hypoperfusion and monitoring for potential further infarction or efficacy of thrombolysis after ischemic stroke is strongly needed.

Socioeconomic importance of stroke Stroke is the first cause of acquired disability, the second cause of dementia and the third cause of death worldwide, and its associated socio-economic costs are astronomic. The burden of stroke is likely to increase, given the aging of the population and the growing incidence of many vascular risk factors. Therefore, rational and effective diagnostic and therapeutic management in stroke patients has potential high long-term clinical and economic consequences.

Current standard therapy after acute ischemic stroke According to the cause of stroke and apart from medical treatment and surgical options in selected cases, the mainstay of therapeutic management of acute ischemic stroke itself usually remain systemic intravenous thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) or selective intraarterial fibrinolysis and mechanical recanalization, both with or without bridging (combined intravenous and intraarterial thrombolysis). In this regard, reperfusion therapy is the only proven treatment for acute ischemic stroke.

Current problems in diagnosis and monitoring of stroke patients At present, CT and MRI are usually applied for diagnosis and follow-up of stroke. However, both CT and MRI achieve simply a baseline study of ischemia occurred and can deliver only a snapshot of brain parenchyma and vessels. Furthermore, whereas CT examination is associated with x-ray radiation and may miss early detection of stroke, MRI is associated with higher costs and is not generally routinely and around-the clock available in all the hospitals. Both imaging methods require transportation and intensive care of the often critically ill patients to the scanning unit for each measurement.

There is unanimous agreement about the need for a bedside assessment of the status of tissue perfusion. Invasive cerebral angiography is indicated in cases of further evaluation of stroke causes and intended endovascular therapy.

Potential of ultrasound perfusion imaging (UPI) What makes contrast enhanced UPI so valuable is the possibility to repeatedly and non-invasively detect brain tissue at risk for infarction by direct brain tissue perfusion assessment and not by surrogate parameters, like blood flow velocity or vessel diameter. Because of the possibility to screen and repeatedly measure the state of perfusion, the chances increase to diagnose and monitor ischemic stroke and to define the appropriate window for treatment. The perfusion analysis would also allow determination of treatment results and guidance of rapid and adequate further therapy.

Objective

The objective of the present study is to assess whether cerebral hypoperfusion can be detected by ultrasound perfusion imaging (UPI) before and after treatment of acute ischemic stroke.

Methods

Patients with acute middle cerebral artery (MCA) territory ischemic stroke are evaluated for potential thrombolysis/thrombectomy according to the Bernese neurologic stroke algorithm. An experienced neurosonographer performs contrast-enhanced ultrasound perfusion imaging (UPI) after prospective study enrollment and specific stroke CT/MRI with perfusion measurement. Clinical status is documented by use of the NIHSS on admission /first day after the intervention. UPI and CT/MRI perfusion data is analyzed. Two different quantification algorithms, standard versus patient-adjusted, are used. Data is analyzed by descriptive statistics using the mean, median and standard deviation of the ROIs. Sensitivity and specificity analyses are calculated using Pearson's chi-square test. Receiver-operator characteristic curves are calculated for UPI/perfusion MRI/CT parameters. Pearson correlation is used to evaluate correlations between absolute values of UPI and MRI TTP data.

Study Type

Observational

Enrollment (Actual)

33

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Bern, Switzerland, 3010
        • Department of Neurosurgery, Bern University Hospital Bern

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The trial population comprises of patients with acute ischemic stroke treated at the University Hospital Bern.

Description

Inclusion Criteria:

  • All patients with an indication for iv thrombolysis or endovascular treatment according to the current stroke guidelines of the University Hospital Bern
  • Age ≥18
  • Written informed consent by patient or next of kin
  • Signed consent of independent physician

Exclusion Criteria

  • Positive pregnancy test and breast feeding
  • Acute coronary syndromes, severe ischemic heart disease (requiring revascularization), severe aortic and mitral valve disease, severe congestive heart failure (NYHA >III/IV)
  • Severe pulmonary or renal dysfunction
  • Known allergy or adverse reaction to contrast material

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
All study participants
Patients with Stroke
Other: Ultrasound perfusion imaging
Dynamic perfusion imaging of brain parenchyma with modern ultrasound is possible with the use of ultrasound contrast media that serve as echo signal amplifier.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of participants with detection of cerebral hypoperfusion before and after thrombolytic treatment and correlation to established diagnostic gold standard CT- or MRI-perfusion studies by measurement of time to peak values
Time Frame: 1 day after intervention
1 day after intervention

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of Patients with Adverse Events as a Measure of Safety and Tolerability and detection of early clinical outcome by NIHSS
Time Frame: 1 day after intervention
1 day after intervention
Quantitative analysis of metric parameters of UPI
Time Frame: 1 day after intervention
1 day after intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Inselspital, Berne

Investigators

  • Principal Investigator: Jürgen Beck, Prof. Dr. med., Department of Neurosurgery, Bern University Hospital Bern

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2012

Primary Completion (Actual)

March 1, 2014

Study Completion (Actual)

April 1, 2016

Study Registration Dates

First Submitted

March 27, 2015

First Submitted That Met QC Criteria

April 8, 2015

First Posted (Estimate)

April 14, 2015

Study Record Updates

Last Update Posted (Estimate)

July 11, 2016

Last Update Submitted That Met QC Criteria

July 8, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 179/12

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Acute Ischemic Stroke

Clinical Trials on Ultrasound perfusion imaging

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Estonia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe