Background8F catheters serve as conduits to provide stable access and support for delivery of 6F aspiration catheters (ACs) in Acute Ischaemic Stroke treatment. Superbore catheters (SBCs) (internal diameter (ID) > 0.088″) are the latest innovation, designed for placement in the middle cerebral artery (MCA). SBCs may improve recanalization via enhanced control of blood pressure and flow, in comparison to balloon guide catheter (BGC) and regular guide catheter (GC) systems.AimTo objectively assess conduit catheter technologies in terms of deliverability, local impact on blood pressure and flow, and clot retrieval success in vitro.MethodsTwo in vitro models were used. Two SBCs, (CEREGLIDE92 and TracStar/Zoom88) and one BGC (EMBOGUARD) were used with 0.071″ ACs, and one GC (NeuronMAX) was evaluated with two 6F ACs (RED68 and SOFIA). M1-MCA occlusions were created with cohesive and friable thrombus analogues. Device tracking and clot retrieval were evaluated by two neurointerventionalists, under physiological haemodynamic conditions.ResultsSBC positioning in the MCA resulted in significant reductions of local blood pressure and flow in comparison to GC systems positioned in the Internal Carotid Artery (p = .000). However, when the SBC could not reach the MCA, they displayed similar haemodynamic control as the GC systems. SBC systems achieved high retrieval success for friable thrombi, likely due to flow reversal in the MCA during aspiration (p = .000). The TracStar/Zoom SBC system had lower rates of cohesive retrieval success due to difficulties in catheter tracking and poor clot alignment with the catheter bevelled tip.ConclusionClot retrieval success is influenced by the location of the conduit for the 6F AC and the design of the AC tip.

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. Ex-vivo clot characterization reveals red blood cell-poorness in clots as a common feature in fibrin-rich, platelet-rich, neutrophil extracellular traps-rich, collagenous or bacteria-rich clots. Preclinical models have evolved alongside ex-vivo clot analysis, demonstrating properties such as increased stiffness, toughness, hardness, and stickiness that hinders retrieval. Imaging markers such as absence of the hyperdense artery sign or susceptibility vessel sign correlate with recalcitrant clots, although reliable predictors of recalcitrant clots remain elusive. Recent innovations, including specifically designed tough clot stent-retrievers such as Nimbus and technologies to improve complete clot ingestion such as super-bore aspiration catheters and cyclic aspiration have shown promise. Yet, a substantial proportion of cases still have difficulty or fail to achieve recanalization. Techniques such as rescue stenting and dual-stent-retriever approaches offer additional strategies but carry risks of vascular injury and complications. Major research limitations include clot deformation during retrieval and the inability to remove some clots. Furthermore, some interactions are poorly understood, such as the biological interaction between the clot and vessel wall or with circulating thrombo-influencing proteins. Overcoming these challenges can pave the pathway for creative solutions to elegantly improve the recanalization of tough clots.

AbstractThis 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. Non-contrast CT and a susceptibility-weighted MRI sequence were used for imaging. The study found that RBC content correlated more accurately than iron content with clot attenuation on CT. There was a strong correlation between Fe III content and RBC percentage in clots. Specifically, changes in RBC content accounted for 64% of the variance in Fe III content (R2 = 0.640; p < .0001). Thrombi with blooming artifacts (BA) displayed higher attenuation on non-contrast CT than those without (73.4 vs. 40 HU, p < .0001) and had the highest RBC and iron contents. The cut-off value of 1242 µg/g of iron predicted blooming artifacts with high sensitivity and specificity. The pH level strongly affected the appearance of blooming artifacts, particularly for negative clots with high RBC content. These findings provide significant insights into the imaging behavior of acute ischemic stroke clots across both imaging modalities and could potentially improve the diagnosis and treatment of acute stroke patients. Furthermore, these results open the possibility for future research aimed at developing pH-modulated therapeutic strategies based on the acid-base state of thrombi.

Background In vitro experiments are critical for understanding the impact of medical devices and techniques on blood vessels and blood flow. However, their interpretation is often limited by anatomical models’ inability to capture the wide range of vessel sizes observed in real‐world practice. The current study aims to address this limitation by describing the distribution of vessel diameters in a real‐world population. Methods This systematic literature review using the PubMed database analyzed cerebral vessel diameters in patients from 2000 to 2022. The diameter measurements of various vessels within the neurovasculature were extracted. Random‐effects meta‐analyses were performed to synthesize vessel diameters across studies. Predicted distributions were generated from the meta‐analytical results. Results Seventy‐six studies were included in the analysis. The M1 segment, internal carotid artery (cervical and communicating segments), A1 segment, V2 segment, V4 segment, and basilar artery had sufficient data for generating predicted distributions of vessel diameters. Predicted mean diameters were as follows: M1 segment, 2.55 ± 0.42 mm (95th interpercentile range [IPR]: 1.71–3.38); internal carotid artery‐cervical segment, 4.74 ± 0.64 mm (95th IPR: 3.49–5.99); internal carotid artery‐communicating segment, 3.40 ± 0.64 mm (95th IPR: 2.15–4.66); A1 segment, 1.89 ± 0.34 mm (95th IPR: 1.23–2.55); V2 segment, 3.36 ± 0.67 mm (95th IPR: 2.05–4.67); V4 segment, 2.42 ± 0.74 mm (95th IPR: 0.98–3.86); and basilar artery, 2.96 ± 0.52 mm (95th IPR: 1.94–3.97). Conclusion Cerebral vessel diameter measurements can vary substantially due to patient‐specific factors and imaging techniques. This literature review highlights the diverse range of vessel sizes observed in different patient populations, emphasizing the need for anatomical models that accurately represent clinical observations.

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. We analyzed 80 thrombi from 80 AIS patients in the RESTORE registry of AIS clots, 40 of which were of CE and 40 of LAA etiology. The localization of BNP and NT-BNP, quantified using immunohistochemistry and immunofluorescence, in AIS-associated white blood cell subtypes was also investigated. We found a statistically significant positive correlation between BNP and NT-proBNP expression levels (Spearman’s rho = 0.668 p < 0.0001 *). We did not observe any statistically significant difference between LAA and CE clots in BNP expression (0.66 [0.13–3.54]% vs. 0.53 [0.14–3.07]%, p = 0.923) or in NT-proBNP expression (0.29 [0.11–0.58]% vs. 0.18 [0.05–0.51]%, p = 0.119), although there was a trend of higher NT-proBNP expression in the LAA clots. It was noticeable that BNP was distributed throughout the thrombus and especially within platelet-rich regions. However, NT-proBNP colocalized with neutrophils, macrophages, and T-lymphocytes, suggesting its association with the thrombo-inflammatory process.

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 in-vitro methodology for evaluating aspiration catheter performance under a variety of pre-defined circumstances, that can be used during catheter development for design optimization. Methods Validation of the in-vitro methodology involved testing four large bore aspiration catheters on recreated challenging vascular access routes derived from patient angiograms. Two experienced neurointerventionalists conducted the tests under controlled physiological and procedural conditions. Each catheter design was evaluated across 30 unique anatomy-procedural set-up combinations. A fifth, prototype large bore catheter was evaluated by trained engineers to assess the applicability of the in-vitro test. Results Results from statistical analysis using a general linear model demonstrated the methodology's effectiveness in detecting significant tracking differences among catheter designs ( p < 0.01). Minimal inter-operator variability was observed ( p = 0.304), while procedural techniques significantly influenced tracking performance ( p < 0.01). The tortuosity of the arterial access route notably impacted catheter performance ( p < 0.01), with anatomical features revealing varying degrees of influence on desirable and undesirable catheter design aspects. Conclusion We successfully developed a test methodology for evaluating the trackability of large bore aspiration catheters intended for treating acute ischemic stroke with large vessel occlusions. This methodology offers a robust approach to pre-clinical design assessment, utilizing anatomical models that simulate real-world vascular challenges to enhance catheter optimization.

Background Predicting a challenging clot when performing mechanical thrombectomy in acute stroke can be difficult. One reason for this difficulty is a lack of agreement on how to precisely define these clots. We explored the opinions of stroke thrombectomy and clot research experts regarding challenging clots, defined as difficult to recanalize clots by endovascular approaches, and clot/patient features that may be indicative of such clots. Methods A modified DELPHI technique was used before and during the CLOTS 7.0 Summit, which included experts in thrombectomy and clot research from different specialties. The first round included open-ended questions and the second and final rounds each consisted of 30 closed-ended questions, 29 on various clinical and clot features, and 1 on number of passes before switching techniques. Consensus was defined as agreement ≥ 50%. Features with consensus and rated ≥ 3 out of 4 on the certainty scale were included in the definition of a challenging clot. Results Three DELPHI rounds were performed. Panelists achieved consensus on 16/30 questions, of which 8 were rated 3 or 4 on the certainty scale, namely white-colored clots (mean certainty score 3.1), calcified clots under histology (3.7) and imaging (3.7), stiff clots (3.0), sticky/adherent clots (3.1), hard clots (3.1), difficult to pass clots (3.1) and clots that are resistant to pulling (3.0). Most panelists considered switching endovascular treatment (EVT) techniques after 2–3 unsuccessful attempts. Conclusion This DELPHI consensus identified 8 distinct features of a challenging clot. The varying degree of certainty amongst the panelists emphasizes the need for more pragmatic studies to enable accurate a priori identification of such occlusions prior to EVT.

The development of high-fidelity in silico simulations of the endovascular thrombectomy (EVT) procedure, the treatment for acute ischemic stroke, is gaining importance for the possibility of investigating the causes of failure of the clinical procedure and optimizing the treatment. This work proposed a novel methodology for a realistic modeling of the thrombus aspiration in a combined EVT procedure, with stent-retriever and proximal aspiration catheter. In the combined EVT procedure, the thrombus is entrapped in the stent struts and is retrieved towards the aspiration catheter. During the retrieval, the thrombus may rotate, and therefore different portions of its surface are subjected to aspiration forces. An automatic algorithm is implemented allowing to redefine the portion of the thrombus surface subjected to the aspiration pressure in different time points of a high-fidelity finite-element EVT simulation. The algorithm updates at each iteration the loaded portion of thrombus surface, by selecting elements aligned with the vascular centerline. The algorithm is applied in a high-fidelity EVT simulation in a patient-like vascular model, demonstrating the ability of obtaining a realistic simulation of thrombus aspiration.

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.Martius Scarlet Blue stain was used to identify the main histological components of the clots.Immunohistochemical staining was used to identify neutrophils, lymphocytes, macrophages, and NETs patterns.The cellular and histological components were quantified using Orbit Image Analysis software.Results: AT clots were larger, with more red blood cells and fewer WBCs than CE clots.AT clots had more lymphocytes and cryptogenic clots had fewer macrophages than other etiologies.Most significantly, CE clots showed higher expression of neutrophils and extracellular web-like NETs compared to AT and cryptogenic clots.There was also a significantly higher distribution of web-like NETs around the periphery of the CE clots while a mixed distribution was observed in AT clots. Conclusion:The difference in neutrophil and NETs expression in clots from different etiologies may provide insight into the mechanism of clot formation.

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). Within each subgroup, 20 patients had developed PTIH and 20 patients showed no signs of hemorrhage. Gross photos of each clot were taken and extracted clot area (ECA) was measured using ImageJ. Immunohistochemistry for S100b was performed and Orbit Image Analysis was used for quantification. Immunofluorescence was performed to investigate co-localization between S100b and T-lymphocytes, neutrophils and macrophages. Chi-square or Kruskal-Wallis test were used for statistical analysis. Results PTIH was associated with higher S100b levels in clots (0.33 [0.08–0.85] vs. 0.07 [0.02–0.27] mm 2 , H1 = 6.021, P = 0.014 * ), but S100b levels were not significantly affected by acute thrombolytic treatment ( P = 0.386). PTIH was also associated with patients having higher NIHSS at admission (20.0 [17.0–23.0] vs. 14.0 [10.5–19.0], H1 = 8.006, P = 0.005) and higher number of passes during thrombectomy (2 [1–4] vs. 1 [1–2.5], H1 = 5.995, P = 0.014 * ). S100b co-localized with neutrophils, macrophages and with T-lymphocytes in the clots. Conclusions Higher S100b expression in AIS clots, higher NIHSS at admission and higher number of passes during thrombectomy are all associated with PTIH. Further investigation of S100b expression in AIS clots by neutrophils, macrophages and T-lymphocytes could provide insight into the role of S100b in thromboinflammation.

Predicting a challenging clot when performing mechanical thrombectomy in acute stroke can be difficult. One reason for this difficulty is a lack of agreement on how to precisely define these clots. We explored the opinions of stroke thrombectomy and clot research experts regarding challenging clots, defined as difficult to recanalize clots by endovascular approaches, and clot/patient features that may be indicative of such clots. A modified DELPHI technique was used before and during the CLOTS 7.0 Summit, which included experts in thrombectomy and clot research from different specialties. The first round included open-ended questions and the second and final rounds each consisted of 30 closed-ended questions, 29 on various clinical and clot features, and 1 on number of passes before switching techniques. Consensus was defined as agreement ≥ 50

Introduction Mechanical thrombectomy in acute ischemic stroke can be delayed or hindered by challenging intracranial access to the clot. However, there is limited information on the various causes, which may be due to a lack of a definition for what constitutes challenging access. The aim of this review was to qualitatively analyze the range of challenging features in the literature and their procedural and clinical outcomes. Materials and Methods A systematic literature search was performed on PubMed and Scopus to identify studies published from January 2014 to October 2020 that reported challenging features and their outcomes separately. Two reviewers independently assessed and extracted data following PRISMA guidelines relevant for a review. To minimize selection bias and increase robustness, only studies with consecutive patients were analyzed for outcomes, although non-consecutive series helped in understanding the variation of reported causes. Where possible for common features, a simple mean was calculated for occurrence rate with descriptive analysis of outcomes for access time (AT), procedure-to-recanalization time (PTR), recanalization success (as measured by each study, typically mTICI 2b-3 at end of procedure), and good clinical outcomes measured as proportion of patients with an mRS 0–2 at 90 days. Results A total of 14 articles were included, out of which only 7 articles reported outcomes with consecutive patients. Considering all studies, definition of challenging access varied across each study, emanating due to their different purposes, evaluating anatomical features (n=6 studies), new catheter evaluations (n=5 studies), workflow (n=2 studies), or specific pathology (n=1 study). In the 7 studies of consecutive patients, 17% (414/2428) of patients displayed one or more challenging feature. Supra-aortic features were reported in 15.6% of patients (333/2126) across 4 studies, listed as carotid loops, turns or kinks (167/2126), carotid atherosclerosis or dissection (166/2126), and tandem lesions or increased take-off angles (from 1 study that performed regression analysis without reporting patient numbers). Procedural and clinical impact included increased PTR by 10–15 minutes (3/3 studies with statistical significance), increased number of passes (1/1 study), decreased rate of successful recanalization by 10–12% (2/3 studies), and decreased rate of good clinical outcomes by 7–14% (1/2 studies). Aortic arch (AA) features were reported in 12.3% of patients (53/432) across 4 studies, listed as type 3 or bovine arch (53/432), left-sided lesions or increased AA cranio-caudal span (from 2 studies that performed regression analysis without reporting patient numbers). Procedural and clinical impact included increased AT by 12–18 min (2/2 studies), increase PTR by 4–5 min (1/1 study), and decreased successful recanalization by 29% (1/1 study). Conclusions Challenging access in mechanical thrombectomy is a significant phenomenon, although there is no consistent definition. The most common occurrence is due to supra-aortic and aortic arch features that vary widely within each study. They often lead to increased access time, procedural time, and decreased successful recanalization and clinical outcomes. Disclosures M. Mirza: 5; C; Cerenovus. J. Penide: None. R. McCarthy: 5; C; Cerenovus. M. Gilvarry: 5; C; Cerenovus.

In-vitro 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. Removal of the occlusive clot in its entirety is the primary goal of the endovascular treatment of LVOs via mechanical thrombectomy (MT) and the medical treatment via thrombolysis. In MT, recanalization after just one pass is associated with better clinical outcomes than procedures that take multiple passes to achieve the same level of recanalization, commonly known as first pass effect (FPE). To achieve this, physicians and engineers are continually investigating new devices and treatment approaches. To distinguish between treatment devices in the pre-clinical setting, test models must also be optimized and expanded become more nuanced and to represent challenging patient cohorts that could be improved through new technology or better techniques. The aim of this paper is to provide a perspective review of the recent advancements in the in-vitro modeling of stroke and to outline how these models need to advance further in future. This review provides an overview of the various in-vitro models used for the modeling of AIS and compares the advantages and limitations of each. In-vitro models remain an extremely useful tool in the evaluation and design of treatment devices, and great strides have been made to improve replication of physiological conditions. However, further advancement is still required to represent the expanding indications for thrombectomy and thrombolysis, and the generation of new thrombectomy devices, to ensure that smaller treatment effects are captured.

Introduction Recent evidence suggests matching the size of the catheter to the vessel diameter promotes higher first-pass complete recanalization, particularly for occlusions in the M1 artery. As catheter sizes continually increase, they may become larger than M1 vessels. The aim of this systematic review was to determine the reported size and variation of the M1 artery internal diameter. Methods A systematic literature search was performed on PubMed to identify studies published from January 2000 until November 2021. Studies measuring the M1 artery size on living human adult patients were included. Multiple cohorts within studies were treated separately. For each cohort, the patient population, reported mean artery size, and imaging modality were extracted. Statistical analysis included a descriptive analysis to calculate the mean and sample variation of the distribution of means, and a one-way ANOVA comparison of means per imaging modality using Tukey's honest significant test for subgroup comparison. Results A total of 20 articles were included with 37 different cohorts measuring 3,560 M1 vessels from a variety of patient populations, including healthy patients (n=12 studies), patients with large vessel occlusions (n=6 studies), or patients with specific neurovascular pathologies (n=2 studies). Distribution of the means was not normal (Anderson-Darling test for normality, p<0.005). A histogram showed a bimodal distribution with 2 peaks. The peak with highest number of cohorts occurred at 2.4mm (equivalent to 0.094' or 7.2F), while the other peak was at 3.0mm (equivalent to 0.118' or 9.0F). The lowest mean was reported as 2.1mm (equivalent to 0.083' or 6.3F) with an interquartile range of 1.9 to 2.3mm, and the highest at 3.42mm (0.135' or 10.2F) with a range of 2.98 to 3.68mm. Subgroup comparison of imaging modalities was not significant (p>0.05) for MRA (µ=2.68 ± 0.41mm from 23 cohorts), CTA (µ=2.56 ± 0.40mm from 4 cohorts), DSA (µ=2.47 ± 0.48mm from 6 cohorts), and combination of MRA & CTA (µ=2.75 ± 0.21mm from 2 cohorts). Only MRI T2 Blood (µ=3.16± 0.11mm from 2 cohorts) reported a larger mean compared to all other imaging modalities (p<0.05). Since only the means of cohorts were analyzed, individual arteries were reported smaller than the smallest mean, and larger than the largest mean. Conclusions There is a wide variation of M1 sizes and imaging modalities reported in the literature from healthy and stroke patients. As catheter sizes increase beyond 6F, their outer diameters may become oversized to the M1 internal diameter. Disclosures M. Mirza: 5; C; Cerenovus. R. McCarthy: 5; C; Cerenovus. M. Gilvarry: 5; C; Cerenovus.

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. The adopted failure criterion is based on maximum principal stress threshold value. If elements of the thrombus exceed this criterion during the retrieval simulation, then they are deleted from the calculation. Comparison with in-vitro tests indicates that the simulation correctly reproduces the procedures predicting thrombus fragmentation in the case of red blood cells rich thrombi, whereas non-fragmentation is predicted for fibrin-rich thrombi. Modeling of balloon guide catheter prevents clot fragments' embolization to further distal territories during MT procedure.

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. The thrombus proteome was analyzed by label-free quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS). MaxQuant v1.5.2.8 and Perseus v.1.6.15.0 were used for bioinformatics analysis. Protein classes were identified using the PANTHER database and the STRING database was used to predict protein interactions. Results:We identified 1,581 protein groups as part of the AIS thrombus proteome. Fourteen significantly differentially abundant proteins across the two etiologies were identified. Four proteins involved in the ubiquitin-proteasome pathway, blood coagulation or plasminogen activating cascade were identified as significantly abundant in LAA clots. Ten proteins involved in the ubiquitin proteasome-pathway, cytoskeletal remodeling of platelets, platelet adhesion or blood coagulation were identified as significantly abundant in cardioembolic clots. Conclusion:Our results outlined a set of 14 proteins for a proof-of-principle characterization of cardioembolic and LAA FFPE clots, advancing the proteome profile of AIS human thrombi and understanding the pathophysiology of 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. Articles reporting consecutive patients were used to calculate a crude failure rate of femoral and alternative accesses. Results A total of 50 articles met the inclusion criteria, totalling 12,838 interventions. Failure to access the occlusion through transfemoral access occurred in 4.4% of patients, most commonly due to challenging supra-aortic vessel anatomy, decreasing to 3.6% when all alternative access routes were attempted. Failed access from alternative routes (direct carotid, radial and brachial approaches) attempted first-line or after failed femoral attempt were reported in 7.3% of patients. The occurrence rate of potentially challenging features (anatomical, diseases or others) ranged from 4.7% to 47.4%, primarily impacting the access time, procedure time, recanalization and clinical outcomes. Conclusion Failure to access the occlusion is a significant contributor to failed recanalization, regardless of access routes. Challenging, but eventually successful access is also a relevant factor in procedural and clinical outcomes; however challenging access requires a universal definition to enable quantification, so that methods for procedural optimization can be critically assessed.

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. Materials and methods: Seventy five 'white' thrombi were selected by visual inspection from a cohort of 760 clots collected as part of the RESTORE registry. Clots were evaluated histopathologically. Results: Quantification of Martius Scarlett Blue stain identified platelets/other as the major component in 'white' clots' (mean of 55% of clot overall composition) followed by fibrin (31%), red blood cells (6%) and white blood cells (3%). 'White' clots contained significantly more platelets/other (p<0.001*) and collagen/calcification (p<0.001*) and less red blood cells (p<0.001*) and white blood cells (p=0.018*) than 'red' clots. The mean platelet and von Willebrand Factor expression was 43% and 24%, respectively. Adipocytes were found in four cases. 'White' clots were significantly smaller (p=0.016*), less hyperdense (p=0.005*) on computed tomography angiography/non-contrast CT and were associated with a smaller extracted clot area (p<0.001*) than 'red' clots. They primarily caused the occlusion of middle cerebral artery, were less likely to be removed by aspiration and more likely to require rescue-therapy for retrieval. Conclusions: 'White' clots represented 14% of our cohort and were platelet, von Willebrand Factor and collagen/calcification-rich. 'White' clots were smaller, less hyperdense, were associated with significantly more distal occlusions and were less successfully removed by aspiration alone than 'red' clots.