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Objectives Thrombus computed tomography (CT) characteristics might be used to assess histopathologic thrombus composition in patients treated with endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). We aimed to assess the variability in thrombus composition that could be predicted with combined thrombus CT characteristics. Methods Thrombi of patients enrolled in the MR CLEAN Registry between March 2014 and June 2016 were histologically analyzed with hematoxylin-eosin staining and quantified for percentages of red blood cells (RBCs) and fibrin/platelets. We estimated the association between general qualitative characteristics (hyperdense artery sign [HAS], occlusion location, clot burden score [CBS]) and thrombus composition with linear regression, and quantified RBC variability that could be explained with individual and combined characteristics with R2. For patients with available thin-slice (≤ 2.5 mm) imaging, we performed similar analyses for general and quantitative characteristics (HAS, occlusion location, CBS, [relative] thrombus density, thrombus length, perviousness, distance from ICA-terminus). Results In 332 included patients, the presence of HAS (aβ 7.8 [95% CI 3.9–11.7]) and shift towards a more proximal occlusion location (aβ 3.9 [95% CI 0.6–7.1]) were independently associated with increased RBC and decreased fibrin/platelet content. With general characteristics, 12% of RBC variability could be explained; HAS was the strongest predictor. In 94 patients with available thin-slice imaging, 30% of RBC variability could be explained; thrombus density and thrombus length were the strongest predictors. Conclusions Quantitative thrombus CT characteristics on thin-slice admission CT improve prediction of thrombus composition and might be used to further guide clinical decision-making in patients treated with EVT for AIS in the future. Key Points • With hyperdense artery sign and occlusion location, 12% of variability in thrombus RBC content can be explained. • With hyperdense artery sign, occlusion location, and quantitative thrombus characteristics on thin-slice (≤ 2.5 mm) non-contrast CT and CTA, 30% of variability in thrombus RBC content can be explained. • Absolute thrombus density and thrombus length were the strongest predictors for thrombus composition.

BackgroundThe optimal management of ipsilateral extracranial internal carotid artery (ICA) stenosis during endovascular treatment (EVT) is unclear. We compared the outcomes of two different strategies: EVT with vs without carotid artery stenting (CAS).MethodsIn this observational study, we included patients who had an acute ischaemic stroke undergoing EVT and a concomitant ipsilateral extracranial ICA stenosis of ≥50% or occlusion of presumed atherosclerotic origin, from the Dutch Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry (2014–2017). The primary endpoint was a good functional outcome at 90 days, defined as a modified Rankin Scale score ≤2. Secondary endpoints were successful intracranial reperfusion, new clot in a different vascular territory, symptomatic intracranial haemorrhage, recurrent ischaemic stroke and any serious adverse event.ResultsOf the 433 included patients, 169 (39%) underwent EVT with CAS. In 123/168 (73%) patients, CAS was performed before intracranial thrombectomy. In 42/224 (19%) patients who underwent EVT without CAS, a deferred carotid endarterectomy or CAS was performed. EVT with and without CAS were associated with similar proportions of good functional outcome (47% vs 42%, respectively; adjusted OR (aOR), 0.90; 95% CI, 0.50 to 1.62). There were no major differences between the groups in any of the secondary endpoints, except for the increased odds of a new clot in a different vascular territory in the EVT with CAS group (aOR, 2.96; 95% CI, 1.07 to 8.21).ConclusionsFunctional outcomes were comparable after EVT with and without CAS. CAS during EVT might be a feasible option to treat the extracranial ICA stenosis but randomised studies are warranted to prove non-inferiority or superiority.

BACKGROUND: Aspirin and unfractionated heparin are often used during endovascular stroke treatment to improve reperfusion and outcomes. However, the effects and risks of anti-thrombotics for this indication are unknown. We therefore aimed to assess the safety and efficacy of intravenous aspirin, unfractionated heparin, both, or neither started during endovascular treatment in patients with ischaemic stroke.METHODS: We did an open-label, multicentre, randomised controlled trial with a 2 × 3 factorial design in 15 centres in the Netherlands. We enrolled adult patients (ie, ≥18 years) with ischaemic stroke due to an intracranial large-vessel occlusion in the anterior circulation in whom endovascular treatment could be initiated within 6 h of symptom onset. Eligible patients had a score of 2 or more on the National Institutes of Health Stroke Scale, and a CT or MRI ruling out intracranial haemorrhage. Randomisation was done using a web-based procedure with permuted blocks and stratified by centre. Patients were randomly assigned (1:1) to receive either periprocedural intravenous aspirin (300 mg bolus) or no aspirin, and randomly assigned (1:1:1) to receive moderate-dose unfractionated heparin (5000 IU bolus followed by 1250 IU/h for 6 h), low-dose unfractionated heparin (5000 IU bolus followed by 500 IU/h for 6 h), or no unfractionated heparin. The primary outcome was the score on the modified Rankin Scale at 90 days. Symptomatic intracranial haemorrhage was the main safety outcome. Analyses were based on intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. This trial is registered with the International Standard Randomised Controlled Trial Number, ISRCTN76741621.FINDINGS: Between Jan 22, 2018, and Jan 27, 2021, we randomly assigned 663 patients; of whom, 628 (95%) provided deferred consent or died before consent could be asked and were included in the modified intention-to-treat population. On Feb 4, 2021, after unblinding and analysis of the data, the trial steering committee permanently stopped patient recruitment and the trial was stopped for safety concerns. The risk of symptomatic intracranial haemorrhage was higher in patients allocated to receive aspirin than in those not receiving aspirin (43 [14%] of 310 vs 23 [7%] of 318; adjusted OR 1·95 [95% CI 1·13-3·35]) as well as in patients allocated to receive unfractionated heparin than in those not receiving unfractionated heparin (44 [13%] of 332 vs 22 [7%] of 296; 1·98 [1·14-3·46]). Both aspirin (adjusted common OR 0·91 [95% CI 0·69-1·21]) and unfractionated heparin (0·81 [0·61-1·08]) led to a non-significant shift towards worse modified Rankin Scale scores.INTERPRETATION: Periprocedural intravenous aspirin and unfractionated heparin during endovascular stroke treatment are both associated with an increased risk of symptomatic intracranial haemorrhage without evidence for a beneficial effect on functional outcome.FUNDING: The Collaboration for New Treatments of Acute Stroke consortium, the Brain Foundation Netherlands, the Ministry of Economic Affairs, Stryker, Medtronic, Cerenovus, and the Dutch Heart Foundation.

In their article, Goyal et al.1 questioned the added benefit of IV thrombolysis (IVT) prior to mechanical thrombectomy (MT) in patients with ischemic stroke and a large vessel occlusion. As we await the results of ongoing randomized trials (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands [MR CLEAN–NO IV], [ISRCTN80619088][1]; Bridging Thrombolysis Versus Direct Mechanical Thrombectomy in Acute Ischemic Stroke [SWIFT DIRECT], [NCT03192332][2]; Direct Intra-arterial Thrombectomy in Order to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals [DIRECT-MT], [NCT03469206][3]), we must rely on observational data with adequate adjustment for potential confounding variables to estimate the value of IVT in MT-eligible patients.2 Goyal et al.1 rightfully stated that no statistical method can completely adjust for allocation bias. However, current American Heart Association guidelines state that a blood pressure above 185/110 mm Hg and impaired hemostasis (direct oral anticoagulant use or international normalized ratio >1.7) are contraindications for IVT.3 These variables have also been associated with worse outcomes4 and, therefore, are true confounders. Much to our surprise, data on baseline blood pressure and hemostasis were not reported in by Goyal et al.,1 and it does not appear that these variables were used in the propensity score matching. We invite the authors to comment on why information on baseline blood pressure and hemostasis was not reported and how this may have affected their results. [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN80619088 [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03192332&atom=%2Fneurology%2F91%2F24%2F1115.atom [3]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03469206&atom=%2Fneurology%2F91%2F24%2F1115.atom

PURPOSE: Vessel-encoded (VE) pseudo-continuous arterial spin labeling (p-CASL) is a territorial ASL (T-ASL) technique to identify the perfusion territories of cerebral arteries. The aim of this study was to validate the output of three Vessel-encoded p-CASL image processing methods, k-means clustering with and without subsequent linear analysis and a Bayesian framework, by comparison with the perfusion maps acquired with super-selective p-CASL. METHODS: The comparison was done quantitatively using the Hausdorff distance and Dice similarity coefficient in the territories of the right and left internal carotid arteries, the basilar artery, and the right and left vertebral arteries. A qualitative comparison was done in the areas of the anterior and posterior circulation, and the deep gray matter. RESULTS: The overall agreement between the Vessel-encoded p-CASL image processing methods and super-selective p-CASL was good; with the difference that the linear analysis and the Bayesian framework were able to detect mixed perfusion. CONCLUSION: Planning-free Vessel-encoded p-CASL with k-means clustering appears suitable as a general purpose T-ASL strategy, but to determine mixed perfusion a combination with linear analysis, or the Bayesian framework is preferable, which are superior in this regard. To accurately determine the perfusion territory of a single vessel, super-selective p-CASL is still recommended.

Intra- and multicenter reproducibility of currently used arterial spin labeling (ASL) methods were assessed at three imaging centers in the Netherlands, equipped with Philips 3TMR scanners. Six healthy participants were scanned twice at each site. The imaging protocol consisted of continuous ASL (CASL), pseudo-continuous ASL (p-CASL) with and without background suppression, pulsed ASL (PASL) with single and multiple inversion times (TIs), and selective ASL for segmentation. Reproducibility was expressed in terms of the coefficient of repeatability and the repeatability index. Voxelwise analysis of variance was performed, yielding brain maps that reflected regional variability. Intra- and multicenter reproducibility were comparable for all methods, except for single TI PASL, with better intracenter reproducibility (F-test of equality of two variances, P

Cerebral perfusion is the basis for the delivery of oxygen and nutrients to the brain. Brain tissue can become damaged when there is a shortage in the blood supply. Basic physiological functions such as synaptic transmission, the membrane ion pump and energy metabolism are disrupted and within minutes can lead to irreversible damage and neurological symptoms. The aim of this thesis was to investigate the ability of arterial spin labeling (ASL) MRI to measure cerebral perfusion in patients with acute stroke and symptomatic large vessel disease of the brain feeding arteries. ASL perfusion imaging is an alternative non-invasive magnetic resonance imaging (MRI) technique for visualizing brain perfusion and quantifying cerebral blood flow that does not require injection of contrast agents. The blood flowing into the brain is used as an endogenous contrast agent by magnetically labeling the inflowing blood with radiofrequency pulses. This thesis consists of two parts. The first part focuses on the application of different ASL-MRI techniques to assess brain perfusion. In patients with acute stroke it is shown that ASL can detect perfusion deficits and perfusion-diffusion mismatch prior to treatment comparable to gadolinium based DSC perfusion imaging (chapter 2). By acquiring a series of perfusion-weighted images at increasing delay times after the initial labeling, ASL is able to measure the inflow of blood into the brain. Although, when compared to H215O PET there was a relative systematic overestimation of cerebral blood flow (chapter 3), ASL can depict the presence and extent of regions with hypoperfusion and increased transit times in patients with carotid artery disease (chapter 4 and 5). The second part of this thesis focuses on assessing the cerebrovascular reactivity by combining ASL perfusion imaging with a vascular challenge. This is a measure of the brain’s capacity to sustain blood flow when perfusion pressure drops. Impairment is associated with increased stroke occurrence. Cerebrovascular reactivity is impaired in patients with a carotid artery stenosis on the side of the stenosis (chapter 6). By using a selective ASL technique that can visualize the flow territories of the brain feeding arteries, it was shown that cerebrovascular reactivity impairment varies throughout the brain (chapter7). Tissue areas fed via collaterals are the most impaired. Both large vessel disease and the occurrence of white matter lesions were furthermore found to have an effect upon white matter hemodynamics (chapter 8). ASL perfusion imaging can be used to visualize the cerebral blood flow and cerebrovascular reactivity. It can be used in both patients with acute stroke and large vessel disease to detect impaired hemodynamics and be used to assess a patient’s risk for future stroke. In the future, ASL may potentially be used to customize medicinal and surgical treatment to individual patient needs

The recommendations of international guidelines for the management of asymptomatic carotid stenosis (ACS) often vary considerably and extend from a conservative approach with risk factor modification and best medical treatment (BMT) alone, to a more aggressive approach with a carotid intervention plus BMT. The aim of the current multispecialty position statement was to reconcile the conflicting views on the topic. A literature review was performed with a focus on data from recent studies. Several clinical and imaging high-risk features have been identified that are associated with an increased long-term ipsilateral ischemic stroke risk in patients with ACS. Such high-risk clinical/imaging features include intraplaque hemorrhage, impaired cerebrovascular reserve, carotid plaque echolucency/ulceration/ neovascularization, a lipid-rich necrotic core, a thin or ruptured fibrous cap, silent brain infarction, a contralateral transient ischemic attack/stroke episode, male patients