Ischemic stroke is caused by a thrombus that blocks an intracranial artery. Brain tissue beyond the blocked artery survives for a variable period of time because of blood and nutrients received ...through tiny vessels called collaterals. Imaging the brain and the vasculature that supplies it is therefore a vital first step in treating patients with acute ischemic stroke. In this review, we focus on current evidence for imaging selection of patients for endovascular therapy in the context of the recently positive clinical trials, such as Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing Computed Tomography to Recanalization Times (ESCAPE), Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME), and Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA). We discuss evidence for and use of the various imaging paradigms available. We discuss how to set up quick and efficient imaging protocols for patient selection and address common concerns about the use of imaging, including time spent, contrast, radiation, and other advantages and disadvantages. Finally, we briefly comment on how imaging can integrate itself within various health systems of care in the future, thereby potentially improving patient outcomes further.
BACKGROUND AND PURPOSE—Recent positive randomized trials of endovascular therapy for ischemic stroke used predominantly stent retrievers. We pooled data to investigate the efficacy and safety of ...stent thrombectomy using the Solitaire device in anterior circulation ischemic stroke.
METHODS—Patient-level data were pooled from trials in which the Solitaire was the only or the predominant device used in a prespecified meta-analysis (SEER Collaboration)Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial (EXTEND-IA), and Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT). The primary outcome was ordinal analysis of modified Rankin Score at 90 days. The primary analysis included all patients in the 4 trials with 2 sensitivity analyses(1) excluding patients in whom Solitaire was not the first device used and (2) including the 3 Solitaire-only trials (excluding ESCAPE). Secondary outcomes included functional independence (modified Rankin Score 0–2), symptomatic intracerebral hemorrhage, and mortality.
RESULTS—The primary analysis included 787 patients401 randomized to endovascular thrombectomy and 386 to standard care, and 82.6% received intravenous thrombolysis. The common odds ratio for modified Rankin Score improvement was 2.7 (2.0–3.5) with no heterogeneity in effect by age, sex, baseline stroke severity, extent of computed tomography changes, site of occlusion, or pretreatment with alteplase. The number needed to treat to reduce disability was 2.5 and for an extra patient to achieve independent outcome was 4.25 (3.29–5.99). Successful revascularization occurred in 77% treated with Solitaire device. The rate of symptomatic intracerebral hemorrhage and overall mortality did not differ between treatment groups.
CONCLUSIONS—Solitaire thrombectomy for large vessel ischemic stroke was safe and highly effective with substantially reduced disability. Benefits were consistent in all prespecified subgroups.Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.
Background
MRI-based selection of patients for acute stroke interventions requires rapid accurate estimation of the infarct core on diffusion-weighted MRI. Typically used manual methods to delineate ...restricted diffusion lesions are subjective and time consuming. These limitations would be overcome by a fully automated method that can rapidly and objectively delineate the ischemic core. An automated method would require predefined criteria to identify the ischemic core.
Aim
The aim of this study is to determine apparent diffusion coefficient-based criteria that can be implemented in a fully automated software solution for identification of the ischemic core.
Methods
Imaging data from patients enrolled in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) study who had early revascularization following intravenous thrombolysis were included. The patients' baseline restricted diffusion and 30–day T2-weighted fluid-attenuated inversion recovery lesions were manually delineated after coregistration. Parts of the restricted diffusion lesion that corresponded with 30-day infarct were considered ischemic core, whereas parts that corresponded with normal brain parenchyma at 30 days were considered noncore. The optimal apparent diffusion coefficient threshold to discriminate core from noncore voxels was determined by voxel-based receiver operating characteristics analysis using the Youden index.
Results
51 045 diffusion positive voxels from 14 patients who met eligibility criteria were analyzed. The mean DWI lesion volume was 24 (± 23) ml. Of this, 18 (± 22) ml was ischemic core and 3 (± 5) ml was noncore. The remainder corresponded to preexisting gliosis, cerebrospinal fluid, or was lost to postinfarct atrophy. The apparent diffusion coefficient of core was lower than that of noncore voxels (P < 0·0001). The optimal threshold for identification of ischemic core was an apparent diffusion coefficient ≤620 × 10−6mm2/s (sensitivity 69% and specificity 78%).
Conclusions
Our data suggest that the ischemic core can be identified with an absolute apparent diffusion coefficient threshold. This threshold can be implemented in image analysis software for fully automated segmentation of the ischemic core.
Perfusion imaging has the potential to select patients most likely to respond to thrombolysis. We tested the correspondence of computed tomography perfusion (CTP)-derived mismatch with ...contemporaneous perfusion-diffusion magnetic resonance imaging (MRI).
Acute ischemic stroke patients 3 to 6 hours after onset had CTP and perfusion-diffusion MRI within 1 hour, before thrombolysis. Relative cerebral blood flow (relCBF) and time to peak of the deconvolved tissue residue function (Tmax) were calculated. The diffusion lesion (diffusion-weighted imaging) was registered to the CTP slabs and manually outlined to its maximal visual extent. Volumetric accuracy of CT-relCBF infarct core (compared with diffusion-weighted imaging) was tested. To reduce false-positive low CBF regions, relCBF core was restricted to voxels within a relative time-to-peak (relTTP) >4 seconds for lesion region of interest. The MR-Tmax >6 seconds perfusion lesion was automatically segmented and registered to CTP. Receiver-operating characteristic analysis determined the optimal CT-Tmax threshold to match MR-Tmax >6 seconds. Agreement of these CT parameters with MR perfusion-diffusion mismatch in coregistered slabs was assessed (mismatch ratio >1.2, absolute mismatch >10 mL, infarct core <70 mL).
In analysis of 49 patients (mean onset to CT, 213 minutes; mean CT to MR, 31 minutes), constraining relCBF <31% within the automated relTTP perfusion lesion region of interest reduced the median magnitude of volumetric error (vs diffusion-weighted imaging) from 47.5 mL to 15.8 mL (P<0.001). The optimal CT-Tmax threshold to match MR-Tmax >6 seconds was 6.2 seconds (95% confidence interval, 5.6-7.3 seconds; sensitivity, 91%; specificity, 70%; area under the curve, 0.87). Using CT-Tmax >6 seconds "penumbra" and relTTP-constrained relCBF "core," CT-based and MRI-based mismatch status was concordant in 90% (kappa=0.80).
Quantitative CTP mismatch classification using relCBF and Tmax is similar to perfusion-diffusion MRI. The greater accessibility of CTP may facilitate generalizability of mismatch-based selection in clinical practice and trials.
Changes in collateral blood flow, which sustains brain viability distal to arterial occlusion, may impact infarct evolution but have not previously been demonstrated in humans. We correlated ...leptomeningeal collateral flow, assessed using novel perfusion magnetic resonance imaging (MRI) processing at baseline and 3 to 5 days, with simultaneous assessment of perfusion parameters. Perfusion raw data were averaged across three consecutive slices to increase leptomeningeal collateral vessel continuity after subtraction of baseline signal analogous to digital subtraction angiography. Changes in collateral quality, Tmax hypoperfusion severity, and infarct growth were assessed between baseline and days 3 to 5 perfusion-diffusion MRI. Acute MRI was analysed for 88 patients imaged 3 to 6 hours after ischemic stroke onset. Better collateral flow at baseline was associated with larger perfusion-diffusion mismatch (Spearman's Rho 0.51, P < 0.001) and smaller baseline diffusion lesion volume (Rho − 0.70, P < 0.001). In 30 patients without reperfusion at day 3 to 5, deterioration in collateral quality between baseline and subacute imaging was strongly associated with absolute (P = 0.02) and relative (P < 0.001) infarct growth. The deterioration in collateral grade correlated with increased mean Tmax hypoperfusion severity (Rho − 0.68, P < 0.001). Deterioration in Tmax hypoperfusion severity was also significantly associated with absolute (P = 0.003) and relative (P = 0.002) infarct growth. Collateral flow is dynamic and failure is associated with infarct growth.
Basilar artery occlusion is a rare and severe condition. The effectiveness of endovascular thrombectomy in patients with basilar artery occlusion was unclear until recently, because these patients ...were excluded from most trials of endovascular thrombectomy for large-vessel occlusion ischaemic stroke.
The Basilar Artery International Cooperation Study (BASICS) and the Basilar Artery Occlusion Endovascular Intervention versus Standard Medical Treatment (BEST) trials, specifically designed to investigate the benefit of thrombectomy in patients with basilar artery occlusion, did not find significant evidence of a benefit of endovascular thrombectomy in terms of disability outcomes at 3 months after stroke. However, these trials suggested a potential benefit of endovascular thrombectomy in patients presenting with moderate-to-severe symptoms. Subsequently, the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) and the Basilar Artery Occlusion Chinese Endovascular (BAOCHE) trials, which compared endovascular thrombectomy versus medical therapy within 24 h of onset, showed clear benefit of endovascular thrombectomy in reducing disability and mortality, particularly in patients with moderate-to-severe symptoms. The risk of intracranial haemorrhage with endovascular thrombectomy was similar to the risk in anterior circulation stroke. Thrombectomy was beneficial regardless of age, baseline characteristics, the presence of intracranial atherosclerotic disease, and time from symptom onset to randomisation. Therefore, the question of whether endovascular thrombectomy is beneficial in basilar artery occlusion now appears to be settled in patients with moderate-to-severe symptoms, and endovascular thrombectomy should be offered to eligible patients.
Key outstanding issues are the potential benefits of endovascular thrombectomy in patients with mild symptoms, the use of intravenous thrombolysis in an extended time window (ie, after 4·5 h of symptom onset), and the optimal endovascular technique for thrombectomy. Dedicated training programmes and automated software to assist with the assessment of imaging prognostic markers could be useful in the selection of patients who might benefit from endovascular thrombectomy. Large international research networks should be built to address knowledge gaps in this field and allow the conduct of clinical trials with fast and consecutive enrolment and a diverse ethnic representation.
IMPORTANCE: Brain-computer interface (BCI) implants have previously required craniotomy to deliver penetrating or surface electrodes to the brain. Whether a minimally invasive endovascular technique ...to deliver recording electrodes through the jugular vein to superior sagittal sinus is safe and feasible is unknown. OBJECTIVE: To assess the safety of an endovascular BCI and feasibility of using the system to control a computer by thought. DESIGN, SETTING, AND PARTICIPANTS: The Stentrode With Thought-Controlled Digital Switch (SWITCH) study, a single-center, prospective, first in-human study, evaluated 5 patients with severe bilateral upper-limb paralysis, with a follow-up of 12 months. From a referred sample, 4 patients with amyotrophic lateral sclerosis and 1 with primary lateral sclerosis met inclusion criteria and were enrolled in the study. Surgical procedures and follow-up visits were performed at the Royal Melbourne Hospital, Parkville, Australia. Training sessions were performed at patients’ homes and at a university clinic. The study start date was May 27, 2019, and final follow-up was completed January 9, 2022. INTERVENTIONS: Recording devices were delivered via catheter and connected to subcutaneous electronic units. Devices communicated wirelessly to an external device for personal computer control. MAIN OUTCOMES AND MEASURES: The primary safety end point was device-related serious adverse events resulting in death or permanent increased disability. Secondary end points were blood vessel occlusion and device migration. Exploratory end points were signal fidelity and stability over 12 months, number of distinct commands created by neuronal activity, and use of system for digital device control. RESULTS: Of 4 patients included in analyses, all were male, and the mean (SD) age was 61 (17) years. Patients with preserved motor cortex activity and suitable venous anatomy were implanted. Each completed 12-month follow-up with no serious adverse events and no vessel occlusion or device migration. Mean (SD) signal bandwidth was 233 (16) Hz and was stable throughout study in all 4 patients (SD range across all sessions, 7-32 Hz). At least 5 attempted movement types were decoded offline, and each patient successfully controlled a computer with the BCI. CONCLUSIONS AND RELEVANCE: Endovascular access to the sensorimotor cortex is an alternative to placing BCI electrodes in or on the dura by open-brain surgery. These final safety and feasibility data from the first in-human SWITCH study indicate that it is possible to record neural signals from a blood vessel. The favorable safety profile could promote wider and more rapid translation of BCI to people with paralysis. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03834857
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