Novel Human Acute Ischemic Stroke Blood Clot Analogs for In Vitro Thrombectomy Testing

Fitzgerald, Seán; Liu, Yang; Dai, Daying; Mereuta, Oana Madalina; Abbasi, Mehdi; Larco, Jorge Arturo; Douglas, Andrew; Kallmes, David F.; Savastano, Luis; Doyle, Karen M.; Brinjikji, Waleed

doi:10.3174/ajnr.a7102

Cited by 21 publications

(27 citation statements)

References 40 publications

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“…4 Coagulation was induced by adding 1 mL of 5% calcium chloride and 10 mL of 10 U/mL thrombin per 10 mL of blood mixture. 7 To simulate LVO, we loaded clot analogs into a syringe and embolized them to the brain via a 0.088-inch guide catheter (Neuron MAX; Penumbra) under physiologic pressure. This clot analog was selected to challenge current thrombectomy devices because fibrin-rich clots have been reported to be associated with more device passes, longer procedure times, and less favorable patient outcomes.…”

Section: Recreation Of Large-vessel Occlusionmentioning

confidence: 99%

“…8 Clot analogs with different histology and tensile properties can also be made by mixing human plasma and red blood cells with different volume ratios. 7,9 Thrombectomy Testing Thrombectomy was performed with a 6F catheter (Sofia Plus; MicroVention) using the direct-aspiration technique or in combination with a stent retriever (Solitaire; Medtronic) using the Solumbra technique. These 2 techniques were selected because they are most often used for thrombectomy on the basis of a survey of neurointerventionalists.…”

Section: Recreation Of Large-vessel Occlusionmentioning

confidence: 99%

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A Thrombectomy Model Based on Ex Vivo Whole Human Brains

Liu¹,

Larco²,

Madhani³

et al. 2021

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE: The persistent challenges in thrombectomy for large-vessel occlusion, such as suboptimal complete recanalization and first-pass effect imply an insufficient understanding of the artery-clot-device interaction. In this study, we present a thrombectomy model using fresh human brains, which can capture the artery-clot-device interaction through concurrent transmural and angiographic visualizations. MATERIALS AND METHODS:Fresh nonfrozen whole adult human brains were collected and connected to a customized pump system tuned to deliver saline flow at a physiologic flow rate and pressure. Angiography was performed to verify the flow in the anterior-posterior and vertebrobasilar circulations and collaterals. Large-vessel occlusion was simulated by embolizing a radiopaque clot analog. Thrombectomy was tested, and the artery-clot-device interactions were recorded by transmural and angiographic videos.RESULTS: Baseline cerebral angiography revealed excellent penetration of contrast in the anterior-posterior and vertebrobasilar circulations without notable arterial cutoffs and with robust collaterals. Small branches (,0.5 mm) and perforating arteries were consistently opacified with good patency. Three device passes were performed to achieve recanalization, with failure modes including elongation, fragmentation, and distal embolization. CONCLUSIONS:This model enables concurrent transmural and angiographic analysis of artery-clot-device interaction in a human brain and provides critical insights into the action mechanism and failure modes of current and upcoming thrombectomy devices.

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Section: Recreation Of Large-vessel Occlusionmentioning

confidence: 99%

Section: Recreation Of Large-vessel Occlusionmentioning

confidence: 99%

A Thrombectomy Model Based on Ex Vivo Whole Human Brains

Liu¹,

Larco²,

Madhani³

et al. 2021

AJNR Am J Neuroradiol

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“…The composition of occlusive clots in acute ischemic stroke has received vast attention through two dimensional (2D) histopathology investigations ( 1 – 3 ). Knowledge about human clots composition allowed valuable developments regarding the preparation of clot analogs ( 4 ) which best reproduce in terms of cellular and fibrin content the composition of clots retrieved from patients. Clot analogs with predefined compositions were successfully used to define the most effective clinical imaging protocols, computed tomography (CT) ( 5 ) or magnetic resonance imaging (MRI) ( 6 ), or to study in vitro thrombectomy techniques ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

“…Knowledge about human clots composition allowed valuable developments regarding the preparation of clot analogs ( 4 ) which best reproduce in terms of cellular and fibrin content the composition of clots retrieved from patients. Clot analogs with predefined compositions were successfully used to define the most effective clinical imaging protocols, computed tomography (CT) ( 5 ) or magnetic resonance imaging (MRI) ( 6 ), or to study in vitro thrombectomy techniques ( 4 ). While clot analogs are a valuable tool for studying clinical imaging and optimizing interventional techniques, the clots retrieved from patients remain the most valuable substrate for research on clot behavior ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

MicroCT Can Characterize Clots Retrieved With Mechanical Thrombectomy From Acute Ischemic Stroke Patients–A Preliminary Report

LaGrange¹,

Braunersreuther²,

Wanke

et al. 2022

Front. Neurol.

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BackgroundCharacterization of the clot occluding the arteries in acute ischemic stroke received ample attention, in terms of elucidating the relationship between the clot composition, its etiology and its amenability for pharmacological treatment and mechanical thrombectomy approaches. Traditional analytical techniques such as conventional 2D histopathology or electron microscopy sample only small parts of the clot. Visualization and analysis in 3D are necessary to depict and comprehend the overall organization of the clot. The aim of this study is to investigate the potential of microCT for characterizing the clot composition, structure, and organization.MethodsIn a pilot study, we analyzed with microCT clots retrieved from 14 patients with acute ischemic stroke. The following parameters were analyzed: overall clot density, clot segmentation with various density thresholds, clot volume.ResultsOur findings show that human clots are heterogeneous in terms of CT intra-clot density distribution. After fixation in formalin, the clots display a shift toward negative values. On average, we found the mean HU values of red clots retrieved from patients to be −153 HU, with SD = 23.8 HU, for the intermediate clots retrieved from patients −193 HU, SD = 23.7 HU, and for the white clots retrieved from patients −229 HU, SD = 64.8 HU.ConclusionOur study shows that volumetric and density analysis of the clot opens new perspectives for clot characterization and for a better understanding of thrombus structure and composition.

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“…For this reason, it is important to characterize the clot ex vivo with imaging techniques similar to those used in clinical setting. Recently, the preparation of analog clots series ( 35 ), spanning a wide range of red blood cells, fibrin, and platelets content, allowed the development of parametric studies which identified MRI sequences ( 36 ) and CT protocols ( 37 ) capable of differentiating different clot types in vitro .…”

Section: Introductionmentioning

confidence: 99%

Multimodality Characterization of the Clot in Acute Stroke

et al. 2021

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Aim: Current treatment of occluded cerebral vessels can be done by a variety of endovascular techniques. Sometimes, the clot responds in varying degrees to the treatment chosen. The Ex vivo characterization of the clot occluding the arteries in acute ischemic stroke can help in understanding the underlying imaging features obtained from pre-treatment brain scans. For this reason, we explored the potential of microCT when combined with electron microscopy for clot characterization. Results were compared to the clinical CT findings.Methods: 16 patients (9 males, 8 females, age range 54–93 years) who were referred to our institution for acute stroke underwent dual-source CT.Results: Clinical CT clots were seen as either iso or hyperdense. This was corroborated with micro-CT, and electron microscopy can show the detailed composition.Conclusion: MicroCT values can be used as an indicator for red blood cells-rich composition of clots. Meaningful information regarding the clot composition and modalities of embedding along the stent retrievers can be obtained through a combination of microCT and electron microscopy.

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Novel Human Acute Ischemic Stroke Blood Clot Analogs for In Vitro Thrombectomy Testing

Cited by 21 publications

References 40 publications

A Thrombectomy Model Based on Ex Vivo Whole Human Brains

A Thrombectomy Model Based on Ex Vivo Whole Human Brains

MicroCT Can Characterize Clots Retrieved With Mechanical Thrombectomy From Acute Ischemic Stroke Patients–A Preliminary Report

Multimodality Characterization of the Clot in Acute Stroke

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