High B Value Diffusion and Stroke (HBS)

This study will include 100 stroke patients with significant penumbra at the acute stage and successfully recanalized thanks to thrombectomy, intravenous thrombolysis or spontaneously. Patients will be explored with the multi-b diffusion sequence on a new 3T research magnet equipped with high gradient system. In this project the investigators hypothesize that diffusion MRI at high and ultra-high b-values could be sensitive enough to quantify selective neuronal loss in the rescued penumbra and to study its relationship with the initial hypoperfusion and its impact in terms of clinical recovery.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Device: Multi-b diffusion sequence MRI

Detailed Description

Thrombectomy has significantly improved the outcome of stroke patients. However, even after successful recanalization residual handicap including post-stroke cognitive and mood disorders impact the quality of life of patients. These symptoms correlate only moderately with the final stroke volume suggesting more widespread dysfunction than what is apparent on standard follow-up MRI. One hypothesis is that the rescued penumbra (i.e.; the tissue showing significant hypoperfusion at the acute stage but that appears normal on conventional imaging at follow up) could exhibit incomplete ischemic injury also known under the term of selective neuronal loss. The concept of selective neuronal loss in the rescued penumbra is admitted based on histological, animal and PET studies but the identification of such a graduation between pan-necrosis and normal tissue is very challenging to capture in vivo with MRI and is typically missed.

This study will prospectively include 100 stroke patients. Patients admitted with significant penumbra at the acute stage and successfully recanalized thanks to thrombectomy thrombolysis or spontaneously will be explored at 24h-to-72h and then at 3 months with the multi-b diffusion sequence. The investigators expect to be able to measure significant modifications within the rescued penumbra as compared to contralateral normal brain by using the advanced but also the simplified diffusion metrics. Investigators will test the impact of duration/severity of the initial hypoperfusion and they will explore the clinical relevance especially in terms of cognitive and mood disorders as measured at 3 months.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • CHU de Bordeaux

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients older than 18 years old
• Cerebral infarct or cerebral hypoperfusion with neurological symptoms within the anterior circulation
• Due to occlusion or stenosis of intracranial carotid artery or its branches and/or middle cerebral artery (MCA) and/or anterior cerebral artery.
• With acute MRI performed within the first 24h and showing significant penumbra defined as ratio between the volumes of critically hypoperfused tissue (defined by Tmax>6s) and the ischemic core (defined by ADC<600 × 10-6 mm2/s) of 1.8 or more, with an absolute difference of 15 mL or more and ischemic core volume of less than 70 mL.
• Successful recanalization by thrombectomy (TICI 2b or 2c or 3) and/or by IV thrombolysis (if within the first 4.5h) or spontaneously.
• Patient/Legally Authorized Representative has signed the Informed Consent form.

Exclusion Criteria:

• History of symptomatic cerebral infarct with functional deficit (pre-stroke modified Rankin Scale score ≥1) to measure the impact of the infarct and selective neuronal loss on long-term outcome without being biased by pre-existing deficits.
• History of severe cognitive impairment (dementia) or DSMIV axis 1 psychiatric disorders that would confound the neurological evaluations.
• Pregnant or breast-feeding women.
• Contraindications to MRI.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: MRI protocol; For stroke patients, the follow-up MRI (named MRI-2) after successfully recanalized thanks to thrombectomy, intravenous thrombolysis or spontaneously, will be performed between 24h and 72h after recanalization on our new Canon 3T research magnet with high gradient system. Patients will be explored for a follow-up evaluation at 3 months with a final MRI (named MRI-3) that will be performed on the Canon 3T research magnet.

Device: Multi-b diffusion sequence MRI; Patients will be explored with the multi-b diffusion sequence on a new 3T research magnet equipped with high gradient system.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Diffusivity (MD) (in 10-9 m2/s)	Computation of Mean Diffusivity (MD) metrics (in 10-9 m2/s) including MDlow for b=1000s/mm2 and pseudo-MDhigh for maps calculated from the highest b-values within the rescued penumbra and within normal contralateral symmetric region of the brain	Up to 72 hours
Mean Diffusivity (MD) (in 10-9 m2/s)	Computation of Mean Diffusivity (MD) metrics (in 10-9 m2/s) including MDlow for b=1000s/mm2 and pseudo-MDhigh for maps calculated from the highest b-values within the rescued penumbra and within normal contralateral symmetric region of the brain	3 month of follow-up.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Kurtosis (MK)	Average of the diffusional kurtosis along all diffusion directions	Up to 72 hours
Mean Kurtosis (MK)	Average of the diffusional kurtosis along all diffusion directions	3 month of follow-up
Mean Diffusivity of the slow component (MDs)	Mean Diffusivity of the slow component (MDs) within the rescued penumbra and within normal contralateral symmetric region	Up to 72 hours
Mean Diffusivity of the slow component (MDs)	Mean Diffusivity of the slow component (MDs) within the rescued penumbra and within normal contralateral symmetric region	3 month of follow-up
Magnetization Transfert Ratio	Magnetization Transfert Ratio maps (MTR=(0-Ms)/M0 x100 where M0 and Ms represent the signal intensity with the saturation prepulse off and on, respectively) within the rescued penumbra and within normal contralateral symmetric region of the brain	Up to 72 hours
Magnetization Transfert Ratio	Magnetization Transfert Ratio maps (MTR=(0-Ms)/M0 x100 where M0 and Ms represent the signal intensity with the saturation prepulse off and on, respectively) within the rescued penumbra and within normal contralateral symmetric region of the brain	3 month of follow-up

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Actual): June 21, 2022
• Study Completion (Actual): June 21, 2022

Study Registration Dates

• First Submitted: March 25, 2019
• First Submitted That Met QC Criteria: April 19, 2019
• First Posted (Actual): April 22, 2019

Study Record Updates

• Last Update Posted (Actual): July 14, 2022
• Last Update Submitted That Met QC Criteria: July 12, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Stroke; High b-value diffusion MRI; Rescued penumbra; Selective neuronal loss.
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: CHUBX 2018/58

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