Abstract TP54: Machine-Learned Characterization of Acute Ischemic Stroke Clots Reveals a Correlation Between Clot Composition and Density on CT

BackgroundCalcified cerebral emboli (CCEs) are a rare cause of acute ischemic stroke (AIS) and are frequently associated with poor outcomes. The presence of dense calcified material enables reliable identification of CCEs using non-contrast CT. However, recanalization rates with the available mechanical thrombectomy (MT) devices remain low.ObjectiveTo recreate a large vessel occlusion involving a CCE using an in vitro silicone model of the intracranial vessels and to demonstrate the feasability of this model to test different endovascular strategies to recanalize an occlusion of the M1 segment of the middle cerebral artery (MCA).MethodsAn in vitro model was developed to evaluate different endovascular treatment approaches using contemporary devices in the M1 segment of the MCA. The in vitro model consisted of a CCE analog placed in a silicone neurovascular model. Development of an appropriate CCE analog was based on characterization of human calcified tissues that represent likely sources of CCEs. Feasibility of the model was demonstrated in a small number of MT devices using four common procedural techniques.ResultsCCE analogs were developed with similar mechanical behavior to that of ex vivo calcified material. The in vitro model was evaluated with various MT techniques and devices to show feasibility of the model. In this limited evaluation, the most successful retrieval approach was performed with a stent retriever combined with local aspiration through a distal access catheter, and importantly, with flow arrest and dual aspiration using a balloon guide catheter.ConclusionCharacterization of calcified tissues, which are likely sources of CCEs, has shown that CCEs are considerably stiffer than thrombus. This highlights the need for a different in vitro AIS model for CCEs than those used for thromboemboli. Consequentially, an in vitro AIS model representative of a CCE occlusion in the M1 segment of the MCA has been developed.

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Characterization of tissue and functional deficits in a clinically translational pig model of acute ischemic stroke

Brain Research ◽

10.1016/j.brainres.2020.146778 ◽

2020 ◽

Vol 1736 ◽

pp. 146778 ◽

Cited By ~ 3

Author(s):

Erin E. Kaiser ◽

Elizabeth S. Waters ◽

Madison M. Fagan ◽

Kelly M. Scheulin ◽

Simon R. Platt ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Pig Model ◽

Functional Deficits

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Characterization of Tauopathy in a Rat Model of Post-Stroke Dementia Combining Acute Infarct and Chronic Cerebral Hypoperfusion

International Journal of Molecular Sciences ◽

10.3390/ijms21186929 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6929

Author(s):

Dong Bin Back ◽

Bo-Ryoung Choi ◽

Jung-Soo Han ◽

Kyoung Ja Kwon ◽

Dong-Hee Choi ◽

...

Keyword(s):

Ischemic Stroke ◽

Cognitive Impairment ◽

Acute Ischemic Stroke ◽

Rat Model ◽

Artery Occlusion ◽

Chronic Cerebral Hypoperfusion ◽

Cerebral Hypoperfusion ◽

Tau Hyperphosphorylation ◽

Post Stroke

Post-stroke dementia (PSD) is a major neurodegenerative consequence of stroke. Tauopathy has been reported in diverse neurodegenerative diseases. We investigated the cognitive impairment and pathomechanism associated with tauopathy in a rat model of PSD by modeling acute ischemic stroke and underlying chronic cerebral hypoperfusion (CCH). We performed middle cerebral artery occlusion (MCAO) surgery in rats to mimic acute ischemic stroke, followed by bilateral common carotid artery occlusion (BCCAo) surgery to mimic CCH. We performed behavioral tests and focused on the characterization of tauopathy through histology. Parenchymal infiltration of cerebrospinal fluid (CSF) tracers after intracisternal injection was examined to evaluate glymphatic function. In an animal model of PSD, cognitive impairment was aggravated when BCCAo was combined with MCAO. Tauopathy, manifested by tau hyperphosphorylation, was prominent in the peri-infarct area when CCH was combined. Synergistic accentuation of tauopathy was evident in the white matter. Microtubules in the neuronal axon and myelin sheath showed partial colocalization with the hyperphosphorylated tau, whereas oligodendrocytes showed near-complete colocalization. Parenchymal infiltration of CSF tracers was attenuated in the PSD model. Our experimental results suggest a hypothesis that CCH may aggravate cognitive impairment and tau hyperphosphorylation in a rat model of PSD by interfering with tau clearance through the glymphatic system. Therapeutic strategies to improve the clearance of brain metabolic wastes, including tau, may be a promising approach to prevent PSD after stroke.

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Metabolomic Characterization of Acute Ischemic Stroke Facilitates Metabolomic Biomarker Discovery

10.21203/rs.3.rs-661365/v1 ◽

2021 ◽

Author(s):

Biao Qi ◽

Yanyu Zhang ◽

Yuhao Zhang ◽

Guoqiang Fei ◽

Ling lin ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Biomarker Discovery ◽

Multiple Reaction Monitoring ◽

Control Group ◽

Healthy Controls ◽

Serum Samples ◽

Multivariate Statistical ◽

Lysine Degradation

Abstract Acute ischemic stroke (AIS) is characterized by a sudden blockage of one of the main arteries supplying blood to the brain, leading to insufficient oxygen and nutrients for brain cells to function properly. Unfortunately, metabolic alterations in the biofluids with AIS are still not well understood. In this study, we performed high-throughput target metabolic analysis on 44 serum samples, including 22 from AIS patients and 22 from healthy controls. Multiple reaction monitoring analysis of 180 common metabolites revealed a total of 29 metabolites changed significantly (VIP>1, P <0.05). Multivariate statistical analysis unraveled a strikingly separation between AIS patients and healthy controls. Comparing AIS with Control group, the contents of argininosuccinic acid, beta-D-glucosamine, glycerophosphocholine, L-abrine, and L-pipecolic acid were down-regulated in AIS patients. 29 out of 112 detected metabolites, enriched in aminoacyl-tRNA biosynthesis, glycerophospholipid metabolism, lysine degradation, phenylalanine, tyrosine and tryptophan biosynthesis metabolic pathways. Collectively, these results will provide a sensitive, feasible diagnostic prospect for AIS patients.

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Abstract TP214: 3D-Electron Microscopy for the Analysis of the Microstructure of Acute Ischemic Stroke Clots

Stroke ◽

10.1161/str.51.suppl_1.tp214 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Seán Fitzgerald ◽

Daying Dai ◽

Asim Rizvi ◽

Karen M Doyle ◽

Ramanathan Kadirvel ◽

...

Keyword(s):

Electron Microscopy ◽

Ischemic Stroke ◽

Red Blood Cells ◽

Acute Ischemic Stroke ◽

Mayo Clinic ◽

Blood Cells ◽

White Blood Cells ◽

Three Dimensional ◽

3D Electron Microscopy

Introduction: Characterization of acute ischemic stroke thrombi has typically focused on the two dimensional (2D) histological characterization of the thrombus. Little is known about the three dimensional (3D) structure of these occlusive thrombi. Electron Microscopy (EM) can be used to obtain 3D information about the organization of clot components. Individual structures can be segmented and qualitative and quantitative information obtained from the clots. Methods: Following IRB approval from Mayo Clinic, acute ischemic stroke clot samples were collected from 10 patients treated at Mayo Clinic. Samples were immediately fixed in fresh modified Trumps fixative solution. A representative fragment of clot was taken and split longitudinally into two pieces; one piece was sent for 3D-EM analysis and the other for histological processing and analysis. Hematoxylin and eosin stain (H&E) and Martius Scarlett Blue (MSB) histological stains were used for conventional histopathology evaluation and components analysis. Immunohistochemical (IHC) staining using anti-CD42b (Platelets) was applied to confirm the presence of platelets in each clot. Serial block-face scanning electron microscopy was used to generate high-resolution three-dimensional images. Results: The 2D morphological features of the clot were identified using H&E, MSB and anti-CD42b staining. The 3D organization of thrombi varies greatly, both within and between clots depending on the constituents. Red Blood Cell-rich areas are mainly composed of Red Blood Cells packaged tightly together, with a small number of Fibrin strands interwoven between the cells. Fibrin-rich areas are characterized by dense networks of fibrin strands along with platelets and White Blood Cells with some sparse Red Blood Cells present. Platelet-rich areas are composed of large volumes of de-granulated platelets, some fibrin stands and white blood cells and an absence of Red Blood Cells. Conclusions: 3D electron microscopy can provide important information on the organization of components within thrombi. This could provide key information on the age and etiology of the thrombus. In addition, it may help to inform thrombolytic treatment and medical device design.

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Abstract TP237: Characterization of Retrieved Thrombus Composition by Morphological, Histopathological and Imaging Analysis in Acute Ischemic Stroke

Stroke ◽

10.1161/str.50.suppl_1.tp237 ◽

2019 ◽

Vol 50 (Suppl_1) ◽

Author(s):

Changhyo Yoon ◽

Young Soo Kim ◽

Seung Kug Baik ◽

Seunguk Jung

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Imaging Analysis

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Identification and characterization of protein marker(s) for diagnosis and prognosis of acute Ischemic stroke patients

Neuroscience Research ◽

10.1016/j.neures.2007.06.584 ◽

2007 ◽

Vol 58 ◽

pp. S240

Author(s):

R.S. Kashyap ◽

A. Nayak ◽

P. Deshpande ◽

H.J. Purohit ◽

G.M. Taori ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Stroke Patients ◽

Protein Marker ◽

Diagnosis And Prognosis ◽

Identification And Characterization

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Characterization of the ‘White’ Appearing Clots that Cause Acute Ischemic Stroke

10.21203/rs.3.rs-45700/v1 ◽

2020 ◽

Author(s):

Oana Madalina Mereuta ◽

Seán Fitzgerald ◽

Rosanna Rossi ◽

Andrew Douglas ◽

Abhay Pandit ◽

...

Keyword(s):

Ischemic Stroke ◽

Red Blood Cells ◽

Acute Ischemic Stroke ◽

Blood Cells ◽

White Blood Cells ◽

Fatty Acid Binding ◽

Blue Stain ◽

Von Willebrand ◽

Willebrand Factor

Abstract Background: Most clots retrieved from patients with acute ischemic stroke are ‘red’ in color and are predominantly composed of red blood cells and fibrin. ‘White’ clots represent a less common entity and their histological composition is largely unknown.The aim of this study was to investigate the composition, imaging and procedural characteristics of ‘white’ clots retrieved by mechanical thrombectomy.Materials and Methods:Nineteen ‘white’ thrombi selected by visual inspection from 293 cases were collected as part of the multi-institutional RESTORE registry. Non-contrast computed tomography (NCCT), histological and immunohistochemical analyses were performed. Components were quantified using Orbit Image Analysis.Results:Quantification of Martius Scarlett Blue stain identified platelets/other as the major component in ‘white’ clots’ (63%) followed by fibrin (26%), red blood cells (7%) and white blood cells (4%). ‘White’ clots presented significantly more platelets/other and less red blood cells compared to the ‘red’ clots which showed a mean of 23% and 44%, respectively. The mean platelet (CD42b) content in ‘white’ clots was 43%; von Willebrand Factor (vWF) mean expression was 38%.Collagen and calcification were associated in one case. Fatty acid binding protein 4 was expressed in two cases.‘White’ clots were also significantly smaller (9.5 versus 12 mm) and less hyperdense (52 versus 61 Hounsfield Units) on NCCT compared to the other cases.Conclusions:‘White’ clots represented 6% of our cohort and are platelet and vWF-rich. Calcification, collagen and adipocytes were found occasionally. ‘White’ clots differ from other clots in composition, size and density on NCCT.

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