Topographic distribution of cerebral infarct probability in patients with acute ischemic stroke: mapping of intra-arterial treatment effect

Boers, Anna M. M.; Berkhemer, Olvert A.; Slump, Cornelis H.; Zwam, Wim H. van; Roos, Yvo B.W.E.M.; Lugt, Aad van der; Oostenbrugge, Robert J. van; Yoo, Albert J.; Dippel, Diederik W.J.; Marquering, Henk A.; Majoie, Charles B. L. M.; Investigators, Clean Registry

doi:10.1136/neurintsurg-2016-012387

Cited by 5 publications

(4 citation statements)

References 28 publications

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“…Boers et al 21 recently described probabilities of infarcts in various topographic distributions following thrombectomy, demonstrating that deeper, end arteriole-supplied regions, such as the basal ganglia and insular cortex, are less likely to be spared than cortex after successful recanalization with mechanical thrombectomy. Even with this lack of benefit to these deeper regions, it might still often be beneficial to treat these patients because of the potentially salvageable cortex.…”

Section: Discussionmentioning

confidence: 99%

Impact of ASPECT scores and infarct distribution on outcomes among patients undergoing thrombectomy for acute ischemic stroke with the ADAPT technique

Hungerford

Hyer

Turk

et al. 2016

J NeuroIntervent Surg

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Patients with moderate-sized core infarcts involving various distributions in either hemisphere can potentially achieve similar good outcomes compared with those with no core infarction at presentation. A treatment algorithm for acute ischemic stroke, which employs hardline ASPECTS thresholds or excludes patients with basal ganglia infarcts, might preclude patients who would potentially benefit from mechanical thrombectomy with ADAPT.

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Section: Discussionmentioning

confidence: 99%

Impact of ASPECT scores and infarct distribution on outcomes among patients undergoing thrombectomy for acute ischemic stroke with the ADAPT technique

Hungerford

Hyer

Turk

et al. 2016

J NeuroIntervent Surg

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“…Collaborations using other novel techniques such as real-time MRI and infarct probability maps may yield improvements in targeting of therapeutics. 44,45 Despite the cross-model translation of this study, there were some notable limitations. As a Phase I study, SAVER-I did not have a control group, and was not powered to show efficacy.…”

Section: Discussionmentioning

confidence: 99%

Intra-arterial verapamil post-thrombectomy is feasible, safe, and neuroprotective in stroke

Fraser

Maniskas

Trout

et al. 2017

J Cereb Blood Flow Metab

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Large vessel ischemic stroke represents the most disabling subtype. While t-PA and endovascular thrombectomy can recanalize the occluded vessel, good clinical outcomes are not uniformly achieved. We propose that supplementing endovascular thrombectomy with superselective intra-arterial (IA) verapamil immediately following recanalization could be safe and effective. Verapamil, a calcium channel blocker, has been shown to be an effective IA adjunct in a pre-clinical mouse focal ischemia model. To demonstrate translational efficacy, mechanism, feasibility, and safety, we conducted a group of translational experiments. We performed in vivo IA dose-response evaluation in our animal stroke model with C57/Bl6 mice. We evaluated neuroprotective mechanism through in vitro primary cortical neuron (PCN) cultures. Finally, we performed a Phase I trial, SAVER-I, to evaluate feasibility and safety of administration in the human condition. IA verapamil has a likely plateau or inverted-U dose-response with a defined toxicity level in mice (LD 50 16-17.5 mg/kg). Verapamil significantly prevented PCN death and deleterious ischemic effects. Finally, the SAVER-I clinical trial showed no evidence that IA verapamil increased the risk of intracranial hemorrhage or other adverse effect/procedural complication in human subjects. We conclude that superselective IA verapamil administration immediately following thrombectomy is safe and feasible, and has direct, dose-response-related benefits in ischemia.

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“…We are extending previous methods to create ischemic core atlases to predict the size and location of the final infarct based on the thrombus location, composition, and collateral score. Furthermore, we are creating probability maps of infarcts that indicate the chance of having an infarct in a specific region based on prior clinical, imaging, and treatment information (34).…”

Section: Vessel Geometry Clot Atlas and Ischemic Core Atlasmentioning

confidence: 99%

In-Silico Trials for Treatment of Acute Ischemic Stroke

et al. 2020

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Despite improved treatment, a large portion of patients with acute ischemic stroke due to a large vessel occlusion have poor functional outcome. Further research exploring novel treatments and better patient selection has therefore been initiated. The feasibility of new treatments and optimized patient selection are commonly tested in extensive and expensive randomized clinical trials. in-silico trials, computer-based simulation of randomized clinical trials, have been proposed to aid clinical trials. In this white paper, we present our vision and approach to set up in-silico trials focusing on treatment and selection of patients with an acute ischemic stroke. The INSIST project (IN-Silico trials for treatment of acute Ischemic STroke, www.insist-h2020.eu) is a collaboration of multiple experts in computational science, cardiovascular biology, biophysics, biomedical engineering, epidemiology, radiology, and neurology. INSIST will generate virtual populations of acute ischemic stroke patients based on anonymized data from the recent stroke trials and registry, and build on the existing and emerging in-silico models for acute ischemic stroke, its treatment (thrombolysis and thrombectomy) and the resulting perfusion changes. These models will be used to design a platform for in-silico trials that will be validated with existing data and be used to provide a proof of concept of the potential efficacy of this emerging technology. The platform will be used for preliminary evaluation of the potential suitability and safety of medication, new thrombectomy device configurations and methods to select patient subpopulations for better treatment outcome. This could allow generating, exploring and refining relavant hypotheses on potential causal pathways (which may follow from the evidence obtained from clinical trials) and improving clinical trial design. Importantly, the findings of the in-silico trials will require validation under the controlled settings of randomized clinical trials.

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Topographic distribution of cerebral infarct probability in patients with acute ischemic stroke: mapping of intra-arterial treatment effect

Abstract: Probability maps intuitively visualize the topographic distribution of infarct probability due to treatment, which makes it a promising tool for estimating the effect of treatment.

Cited by 5 publications

References 28 publications

Impact of ASPECT scores and infarct distribution on outcomes among patients undergoing thrombectomy for acute ischemic stroke with the ADAPT technique

Impact of ASPECT scores and infarct distribution on outcomes among patients undergoing thrombectomy for acute ischemic stroke with the ADAPT technique

Intra-arterial verapamil post-thrombectomy is feasible, safe, and neuroprotective in stroke

In-Silico Trials for Treatment of Acute Ischemic Stroke

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