Investigation of Brain Blood Flow Changes in Acute Ischemic Stroke Patients After Successful Endovascular Thrombectomy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Comparison of the BOLD-CVR signal with the functional outcome at 3 months
研究概览
简要总结
Introduction:
Endovascular thrombectomy (EVT) is an effective treatment strategy to mitigate the ischemic tissue damage caused by the acute cerebral large-vessel occlusion. However, in clinical practice, nearly half of the patients do not experience adequate neurological improvement despite successful recanalization - a phenomenon termed reperfusion failure or clinically ineffective reperfusion. Given the clinical relevance of this phenomenon and the absence of a standardized imaging diagnostic method to identify it, our project aims to explore the potential role of blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) as novel imaging biomarker for studying reperfusion failure.
Study population:
Adult patients with acute ischemic stroke of the ICA, MCA or with tandem occlusion who have undergone a successful recanalization, described as mTICI score ≥2b.
Objective(s):
Primary objective: to longitudinally observe blood flow changes derived from BOLD-CVR imaging following successful endovascular thrombectomy in patients with large-vessel occlusion acute ischemic stroke (LVO-AIS) during the early post-treatment phase and assess their association with clinical outcome 90 days post-EVT.
Secondary objective: to compare BOLD-CVR findings with those obtained from the clinical standard dynamic susceptibility contrast (DSC) MR perfusion imaging acquired in the same examination session as well as other imaging techniques included in the standard post-treatment imaging protocol at our institution.
Outcomes:
Clinical outcomes:
- 90-day functional outcome.
- Functional outcome at hospital discharge.
- Neurological deterioration during hospitalization.
- Radiologically confirmed haemorrhagic transformation within the reperfused tissue.
- Radiologically confirmed infarct lesion progression within the reperfused tissue.
- Additionally, DSC MR perfusion imaging parameters and other standard hemodynamic imaging parameters will be considered as imaging outcomes
Study design:
Single-center prospective observational cohort study
Measurements and procedures:
Included patients will undergo a total of 3 BOLD-CVR examinations: 72 hours, 7 days, and 90 days after EVT. Participation in the final examination will mark the end of the subject's involvement in the study. Clinical outcomes will be prospectively collected as per established institutional patient management protocols: during hospitalization, at discharge, and at the cerebrovascular outpatient clinic at 3 months.
Number of Participants:
Target sample size: 100 patients
Given the observational study design and exploratory nature of this project, no sample size calculation can be performed. The provided target sample size (N = 100) has been estimated considering the inclusion of as many consecutive subjects as possible.
Study period: 2.5 years The investigators aim to enroll a target sample size of 100 patients over a period of 2.5 years. This translates to an inclusion of 3-4 patients per month, with the last three months allocated for the follow-up of the last included patients.
Study Centre:
Clinical Neuroscience Center, Department of Neurosurgery, University Hospital Zurich
Statistical Considerations:
The association between BOLD-CVR findings and clinical outcomes will be investigated using regression analyses.
详细描述
Introduction:
Acute ischemic stroke (AIS) is a significant global health concern representing the second-leading cause of death and the third-leading cause of disability. In up to 46% of the cases, AIS is caused by the acute occlusion of a large cerebral vessel, leading to loss of blood flow to a specific part of the brain (i.e., tissue ischemia) and resulting in severe neurological deficits. The burden of these deficits and ischemic tissue damage may be significantly reduced or even completely reversed with endovascular thrombectomy (EVT), a procedure aimed at reopening the blocked vessel by removing the blood clot (recanalization) and restoring brain blood flow. However, in clinical practice, nearly half of the patients do not experience adequate neurological improvement despite successful recanalization - a phenomenon termed reperfusion failure or clinically ineffective reperfusion. This condition is characterized by progression of brain damage, hemorrhagic transformation of the infarcted area, and poor clinical scores in the short- and long-term. Given its clinical relevance, efforts have been made to better understand this phenomenon. Several studies in animal models have identified various possible pathophysiological mechanisms that may contribute to reperfusion failure, including microvascular damage, inflammatory response, microvascular occlusion and neurovascular dysfunction. Impaired brain tissue autoregulation appears to be one hemodynamic condition that characterizes reperfusion failure and links part of these potential mechanisms. Recently, numerous imaging techniques have been proposed to investigate reperfusion failure in clinical patient populations, but, so far, the number of clinical studies remains limited and none imaging modality has emerged as superior. Identifying the best imaging biomarker to study these patients is of utmost importance because a deeper understanding of hemodynamic tissue changes following EVT and their association with clinical outcomes could help identify patients at higher risk for developing reperfusion failure. Such insights may potentially lead to personalized neuroprotective treatment strategies, ultimately improving clinical outcome after EVT.
BOLD-CVR is a magnetic resonance imaging (MRI) technique, suitable for patients with AIS, capable of measuring brain tissue's ability to regulate blood flow changes (i.e., autoregulation). This technique involves the administration of a standardized, reproducible, and safe carbon dioxide (CO2) respiratory challenge through the RespirActTM gas blender system during BOLD functional MRI (fMRI) sequence acquisition. CO2 administration acts as vasodilatory stimulus, inducing a blood flow increase in brain regions with preserved autoregulation. Conversely, in regions with impaired autoregulation, insufficient blood flow augmentation or even a paradoxical decrease may occur. This phenomenon, known as "steal phenomenon", represents an indicator of severe tissue hemodynamic suffering. Changes in cerebral blood flow induced by the CO2 stimulus are detected through alterations in the BOLD fMRI signal, which reflect variations in the oxy-/deoxyhemoglobin ratio at tissue level. Deoxyhemoglobin molecules exhibit paramagnetic properties, affecting the T2/T2* relaxation time in 3 Tesla MRI, while oxyhemoglobin molecules have no such effect. Consequently, shifts in the oxy-/deoxyhemoglobin ratio caused by blood flow changes lead to alterations in the BOLD fMRI signal. In this way, the combination of BOLD fMRI sequence with a standardized CO2 stimulus allows for the precise measurement of brain tissue hemodynamic changes with high temporal and spatial resolution, and high reproducibility.
In this project, the investigators aim to study the role of blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) as novel imaging biomarker to investigate reperfusion failure. The investigators thereby integrate the BOLD-CVR technique into the standard post-treatment imaging assessment of patients with LVO-AIS who have undergone EVT at our institution and examine the relationship between BOLD-CVR signals and clinical outcomes.
Project objectives and design:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female subjects >18 years old.
- •Acute ischemic stroke related to a new occlusion of the internal carotid artery, middle cerebral artery (M1- and/or M2-segment), or both.
- •Eligibility and performance of endovascular thrombectomy.
- •Achievement of successful recanalization, defined as mTICI score ≥2b
- •Written informed consent of the patient or when the patient is not able to participate in the consenting procedure, the written authorization of a family member. Foreign speaking patients should be included by a person with sufficient German language proficiency to act as a translator.
排除标准
- •Documented evidence or a confirmed willingness of the patient not to participate in any scientific study.
- •Standard contraindications for MRI, such as pacemaker, metallic prothesis, glaucoma, metallic tattoo dyes, verbal confirmed pregnancy. Unwilling or unable to cooperate with breathing manoeuvres.
- •Major cardiopulmonary diseases, such as severe uncontrolled asthma bronchiale, severe chronic obstructive lung disease (i.e., GOLD stage ≥III), diffuse interstitial lung disease, pulmonary embolism, acute/subacute myocardial infarction, or severe heart failure (i.e., NYHA class ≥III).
- •Symptomatic increased intracranial pressure.
- •Presence of intracranial haemorrhage type ≥2 according to the Heidelberg classification.
- •New onset of seizure.
研究组 & 干预措施
Patients with an acute ischemic stroke of the ICA, MCA or both with successful revascularization
- Male and female subjects >18 years old.
- Acute ischemic stroke related to a new occlusion of the internal carotid artery, middle cerebral artery (M1- and/or M2-segment), or both.
- Eligibility and performance of endovascular thrombectomy.
- Achievement of successful recanalization, defined as mTICI score ≥2b
- Written informed consent of the patient or when the patient is not able to participate in the consenting procedure, the written authorization of an independent doctor not involved in the research project is requested to safeguard the interests of the patients (in that case, post hoc written informed consent of the patient or next of kin had to be obtained). Foreign speaking patients should be included by a person with sufficient German language proficiency to act as a translator.
干预措施: No planned intervention (Other)
结局指标
主要结局
Comparison of the BOLD-CVR signal with the functional outcome at 3 months
时间窗: Comparison of the BOLD CVR signal obtained in the MRI performed within 72 hours after thrombectomy with the functional outcome at three months after intervention (mRS)
Following a published pipeline, BOLD-CVR values per voxel are obtained through a voxel-wise linear regression analysis between the end-tidal CO₂ time course and the BOLD fMRI signal time course. BOLD-CVR is expressed as the percent BOLD signal change per mmHg CO₂ (%BOLD signal change/mmHg CO₂).9 Predefined anatomical brain masks are applied to delineate three regions of interest: the whole brain, the ipsilateral hemisphere, and the territory of the middle cerebral artery (MCA). These masks are overlaid on the BOLD-CVR maps, and the average BOLD-CVR value is calculated for each region, resulting in average BOLD-CVR values for the whole brain, the ipsilateral hemisphere, and the MCA territory. The functional outcome at 90 days post-EVT will be assessed with the mRS score.
次要结局
- Comparison of the BOLD CVR signal with the National Institutes of Health Stroke Scale (NIHSS)(at 7 days)
- Comparison of the BOLD-CVR signal with the Modified Rankin Scale (MRS)(at 7 days)
- Comparison of the BOLD CVR Signal with neurological deterioration during hospitalization(Time Frame between the thrombectomy and 7 days post-EVT)
- Comparison of the BOLD-CVR signal with the dynamic susceptibility contrast (DSC) MR perfusion imaging signal parameters(With 72 hours after thrombectomy; Within 1 week after thrombectomy; at 90 days after thrombectomy.)
- Comparison of the BOLD-CVR Signal with the Quantitative Digital Subtraction Angiography signs(Comparison of the BOLD-CVR signal performed 72 hours after thrombectomy with the intraprocedural quantitative Digital Subtraction Angiography signs (ex. capillary blush, early venous filling, etc.))
- Comparison of the BOLD CVR signal with radiologically confirmed hemorrhagic transformation within the reperfused tissue(Within 72 hours after thrombectomy; Within 7 days after thrombectomy; at 90 days after thrombectomy.)
- Comparison of the BOLD-CVR Signal with radiologically confirmed infarct lesion progression within the reperfused tissue(Within 72 hours after thrombectomy; Within 7 days after Thrombectomy; at 90 days after thrombectomy.)
- Longitudinal comparison of the BOLD-CVR Signal over time(Longitudinal comparison of BOLD-CVR signal across three timepoints: within 72 hours, 7 days, and 90 days after thrombectomy.)
- Comparison of the BOLD-CVR Signal with Systolic blood flow velocities and pulsatility index in the middle cerebral artery (MCA) ipsilateral to the ischemic tissue side.(The neuroangiologic examination (where the Systolic blood flow velocities and pulsatility index in the MCA are measured) is conducted between the thrombectomy procedure and hospital dischage, typically on the day following the intervention.)
研究者
Jorn Fierstra
Prof Dr. med., PhD
University of Zurich