Unmet Needs in Acute Ischemic Stroke: Overcoming Recalcitrant Clots.

Endovascular thrombectomy has revolutionized acute ischemic stroke treatment, significantly improving recanalization rates. However, up to 20% of cases involve recalcitrant clots that fail to recanalize or require multiple passes, negatively impacting clinical outcomes. This review explores the multifaceted nature of these challenging clots, including insights from preclinical, imaging, and clinical studies, with strategies to overcome them.

Ironing out differences in attenuation and blooming artifact in acute stroke thrombi.

This study aims to improve our understanding of acute ischemic stroke clot imaging by integrating CT attenuation information with MRI susceptibility signal of thrombi. For this proof-of-principle experimental study, fifty-seven clot analogs were produced using ovine venous blood with a broad histological spectrum. Each clot analog was analyzed to determine its RBC content and chemical composition, including water, Fe III, sodium, pH, and pO2.

An method for comparative analysis of aspiration catheter tracking performance.

Background And Purpose: Mechanical thrombectomy (MT) for acute ischemic stroke (AIS) relies on efficient tracking of aspiration catheters through complex vascular anatomies. Differences in catheter design lead to variation in tracking performance which may only become apparent after use in patients. We developed an methodology for evaluating aspiration catheter performance under a variety of pre-defined circumstances, that can be used during catheter development for design optimization.

Investigating the Role of Brain Natriuretic Peptide (BNP) and N-Terminal-proBNP in Thrombosis and Acute Ischemic Stroke Etiology.

The need for biomarkers for acute ischemic stroke (AIS) to understand the mechanisms implicated in pathological clot formation is critical. The levels of the brain natriuretic peptides known as brain natriuretic peptide (BNP) and NT-proBNP have been shown to be increased in patients suffering from heart failure and other heart conditions. We measured their expression in AIS clots of cardioembolic (CE) and large artery atherosclerosis (LAA) etiology, evaluating their location inside the clots, aiming to uncover their possible role in thrombosis.

White blood cell subtypes and neutrophil extracellular traps content as biomarkers for stroke etiology in acute ischemic stroke clots retrieved by mechanical thrombectomy.

Background: Lymphocytes, macrophages, neutrophils, and neutrophil extracellular traps (NETs) associate with stroke risk factors and form a thrombus through different mechanisms. We investigated the total WBCs, WBC subtypes and NETs composition in acute ischemic stroke (AIS) clots to identify possible etiological differences that could help us further understand the process of thrombosis that leads to AIS.

Methods: AIS clots from 100 cases each of atherothrombotic (AT), cardioembolic (CE) and cryptogenic stroke etiology were collected per-pass as part of the CÚRAM RESTORE registry of AIS clots.

S100b in acute ischemic stroke clots is a biomarker for post-thrombectomy intracranial hemorrhages.

Background And Purpose: Post-thrombectomy intracranial hemorrhages (PTIH) are dangerous complications of acute ischemic stroke (AIS) following mechanical thrombectomy. We aimed to investigate if S100b levels in AIS clots removed by mechanical thrombectomy correlated to increased risk of PTIH.

Methods: We analyzed 122 thrombi from 80 AIS patients in the RESTORE Registry of AIS clots, selecting an equal number of patients having been pre-treated or not with rtPA (40 each group).

Combined stent-retriever and aspiration intra-arterial thrombectomy performance for fragmentable blood clots: A proof-of-concept computational study.

Mechanical thrombectomy (MT) treatment of acute ischemic stroke (AIS) patients typically involves use of stent retrievers or aspiration catheters alone or in combination. For in silico trials of AIS patients, it is crucial to incorporate the possibility of thrombus fragmentation during the intervention. This study focuses on two aspects of the thrombectomy simulation: i) Thrombus fragmentation on the basis of a failure model calibrated with experimental tests on clot analogs; ii) the combined stent-retriever and aspiration catheter MT procedure is modeled by adding both the proximal balloon guide catheter and the distal access catheter.

A Review of the Advancements in the Modelling of Acute Ischemic Stroke and Its Treatment.

neurovascular models of large vessel occlusions (LVOs) causing acute ischemic stroke (AIS) are used extensively for pre-clinical testing of new treatment devices. They enable physicians and engineers to examine device performance and the response of the occlusion to further advance design solutions for current unmet clinical needs. These models also enable physicians to train on basic skills, to try out new devices and new procedural approaches, and for the stroke team to practice workflows together in the comfort of a controlled environment in a non-clinical setting.

Potential Biomarkers of Acute Ischemic Stroke Etiology Revealed by Mass Spectrometry-Based Proteomic Characterization of Formalin-Fixed Paraffin-Embedded Blood Clots.

Background And Aims: Besides the crucial role in the treatment of acute ischemic stroke (AIS), mechanical thrombectomy represents a unique opportunity for researchers to study the retrieved clots, with the possibility of unveiling biological patterns linked to stroke pathophysiology and etiology. We aimed to develop a shotgun proteomic approach to study and compare the proteome of formalin-fixed paraffin-embedded (FFPE) cardioembolic and large artery atherosclerotic (LAA) clots.

Methods: We used 16 cardioembolic and 15 LAA FFPE thrombi from 31 AIS patients.

Aspects of ischemic stroke biomechanics derived using ex-vivo and in-vitro methods relating to mechanical thrombectomy.

Establishing the underlying biomechanics of acute ischemic stroke (AIS) and its treatment is fundamental to developing more effective clinical treatments for one of society's most impactful diseases. Recent changes in AIS management, driven by clinical evidence of improved treatments, has already led to a rapid rate of innovation, which is likely to be sustained for many years to come. These unprecedented AIS triage and treatment innovations provide a great opportunity to better understand the disease.

Correlation between acute ischaemic stroke clot length before mechanical thrombectomy and extracted clot area: Impact of thrombus size on number of passes for clot removal and final recanalization.

Introduction: We assessed the correlation between thrombus size before and after mechanical thrombectomy, measured as length by Computed Tomography Angiography/Non-Contrast Computed Tomography (CTA/NCCT) and Extracted Clot Area, ECA, respectively. We also assessed the influence of thrombus size on the number of passes required for clot removal and final recanalization outcome.

Materials And Methods: Acute ischaemic stroke (AIS) thrombi retrieved by mechanical thrombectomy from 500 patients and data of clot length by CTA/NCCT were collected from three hospitals in Europe.

Systematic Review on Endovascular Access to Intracranial Arteries for Mechanical Thrombectomy in Acute Ischemic Stroke.

Purpose: In acute ischemic stroke for large vessel occlusions, delayed or failed access to intracranial occlusions has a negative impact on procedural and clinical outcomes. The aim of this review is to identify and quantify access failures and challenges in mechanical thrombectomy.

Methods: A systematic literature review of PubMed and Scopus databases from January 2014 to October 2020 was performed.

Measuring the effect of thrombosis, thrombus maturation and thrombolysis on clot mechanical properties in an in-vitro model.

Changes in acute ischemic stroke thrombi structure and composition may result in significant differences in treatment responsiveness. Ischemic stroke patients are often treated with a thrombolytic agent to dissolve thrombi, however these patients may subsequently undergo mechanical thrombectomy to remove the occlusive clot. We set out to determine if rt-PA thrombolysis treatment of blood clots changes their mechanical properties, which in turn may impact mechanical thrombectomy.

Characterization of the 'White' Appearing Clots that Cause Acute Ischemic Stroke.

Objectives: Most clots retrieved from patients with acute ischemic stroke are 'red' in color. 'White' clots represent a less common entity and their histological composition is less known. Our aim was to investigate the composition, imaging and procedural characteristics of 'white' clots retrieved by mechanical thrombectomy.

A new compressible hyperelastic model for the multi-axial deformation of blood clot occlusions in vessels.

Mechanical thrombectomy can be significantly affected by the mechanical properties of the occluding thrombus. In this study, we provide the first characterisation of the volumetric behaviour of blood clots. We propose a new hyperelastic model for the volumetric and isochoric deformation of clot.

Blood clot fracture properties are dependent on red blood cell and fibrin content.

Thrombus fragmentation during endovascular stroke treatment, such as mechanical thrombectomy, leads to downstream emboli, resulting in poor clinical outcomes. Clinical studies suggest that fragmentation risk is dependent on clot composition. This current study presents the first experimental characterization of the composition-dependent fracture properties of blood clots, in addition to the development of a predictive model for blood clot fragmentation.

Applicability assessment of a stent-retriever thrombectomy finite-element model.

An acute ischaemic stroke appears when a blood clot blocks the blood flow in a cerebral artery. Intra-arterial thrombectomy, a mini-invasive procedure based on stent technology, is a mechanical available treatment to extract the clot and restore the blood circulation. After stent deployment, the clot, trapped in the stent struts, is pulled along with the stent towards a receiving catheter.

Per-pass analysis of acute ischemic stroke clots: impact of stroke etiology on extracted clot area and histological composition.

Background: Initial studies investigating correlations between stroke etiology and clot composition are conflicting and do not account for clot size as determined by area. Radiological studies have shown that cardioembolic strokes are associated with shorter clot lengths and lower clot burden than non-cardioembolic clots.

Objective: To report the relationship between stroke etiology, extracted clot area, and histological composition at each procedural pass.

Large Artery Atherosclerotic Clots are Larger than Clots of other Stroke Etiologies and have Poorer Recanalization rates.

Objectives: There is a paucity of knowledge in the literature relating to the extent of clot burden and stroke etiology. In this study, we measured the Extracted Clot Area (ECA) retrieved during endovascular treatment (EVT) and investigated relationships with suspected etiology, administration of intravenous thrombolysis and recanalization.

Materials And Methods: As part of the multi-institutional RESTORE registry, the ECA retrieved during mechanical thrombectomy was quantified using ImageJ.

The administration of rtPA before mechanical thrombectomy in acute ischemic stroke patients is associated with a significant reduction of the retrieved clot area but it does not influence revascularization outcome.

Both intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are evidence-based treatments for acute ischemic stroke (AIS) in selected cases. Recanalization may occur following IVT without the necessity of further interventions or requiring a subsequent MT procedure. IVT prior to MT (bridging-therapy) may be associated with benefits or hazards.

Investigating the Mechanical Behavior of Clot Analogues Through Experimental and Computational Analysis.

With mechanical thrombectomy emerging as the new standard of care for stroke treatment, clot analogues provide an extremely useful tool in the testing and design of these treatment devices. The aim of this study is to characterise the mechanical behavior of thrombus analogues as a function of composition. Platelet-contracted clot analogues were prepared from blood mixtures of various hematocrits.

Clot Analog Attenuation in Non-contrast CT Predicts Histology: an Experimental Study Using Machine Learning.

Exact histological clot composition remains unknown. The purpose of this study was to identify the best imaging variables to be extrapolated on clot composition and clarify variability in the imaging of thrombi by non-contrast CT. Using a CT-phantom and covering a wide range of histologies, we analyzed 80 clot analogs with respect to X-ray attenuation at 24 and 48 h after production.

Development of an in vitro model of calcified cerebral emboli in acute ischemic stroke for mechanical thrombectomy evaluation.

: BACKGROUND: Calcified 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.