Interhemispheric Contralateral Transcallosal Approach to a Giant Thalamic Cavernous Malformation: 2-Dimensional Operative Video.

Thalamic cavernous malformations are challenging lesions to approach given their deep location and proximity to eloquent neurovascular structures. Several approaches to this region exist, and small nuances in the location of the lesion dictate different surgical trajectories. For cavernous malformations presenting to the superomedial surface of the thalamus, the interhemispheric transcallosal approach affords an excellent trajectory as the anterior two-thirds of the superomedial thalamus constitutes the lateral aspect of the floor of the body of the lateral ventricle. In addition, when the cavernous malformation extends laterally, the contralateral adjunct of the interhemispheric transcallosal approach provides optimal visualization of the lateral aspect of the lesion. In this video, we present the case of a 31-year-old woman who presented to our institution with a giant hemorrhagic thalamic cavernous malformation that resulted in rapid neurological decline characterized by ataxia, right hemiparesis, and diplopia. The cavernous malformation was removed using an interhemispheric contralateral transcallosal approach. The patient had near complete resolution of her preoperative deficits with mild residual weakness in her right hand at 3-month follow-up. At 3-year follow-up, magnetic resonance imaging revealed no active cavernous malformation, and the patient had no recurrence of symptoms. This manuscript was conducted in accordance with the ethical standards of our institution's Institutional Review Board. The patient gave informed consent for surgery and video recording.

Strategies to Improve Drug Delivery Across the Blood-Brain Barrier for Glioblastoma.

PURPOSE OF REVIEW: Glioblastoma remains resistant to most conventional treatments. Despite scientific advances in the past three decades, there has been a dearth of effective new treatments. New approaches to drug delivery and clinical trial design are needed. RECENT FINDINGS: We discuss how the blood-brain barrier and tumor microenvironment pose challenges for development of effective therapies for glioblastoma. Next, we discuss treatments in development that aim to overcome these barriers, including novel drug designs such as nanoparticles and antibody-drug conjugates, novel methods of drug delivery, including convection-enhanced and intra-arterial delivery, and novel methods to enhance drug penetration, such as blood-brain barrier disruption by focused ultrasound and laser interstitial thermal therapy. Lastly, we address future opportunities, positing combination therapy as the best strategy for effective treatment, neoadjuvant and window-of-opportunity approaches to simultaneously enhance therapeutic effectiveness with interrogation of on-treatment biologic endpoints, and adaptive platform and basket trials as imperative for future trial design. New approaches to GBM treatment should account for the blood-brain barrier and immunosuppression by improving drug delivery, combining treatments, and integrating novel clinical trial designs.

Arteriovenous shunts of the cervical spine: patient demographics, presentation, patterns of high-risk venous drainage, and updated classification.

BACKGROUND: Intracranial dural arteriovenous (AV) fistula classifications focus on presence/absence of retrograde flow in the cortical veins of the brain as this angiographic finding portends a worse prognosis. However, prior categorization systems of AV shunts in the spine do not incorporate these features. We propose an updated classification for spinal shunting lesions that terms any shunting lesion with retrograde flow in any cortical vein of the brain or spinal cord medullary vein as "high risk". To present this classification, we analyzed our center's most recent experience with cervical spine shunting lesions. METHODS: The electronic medical record at our institution was reviewed to identify shunting lesions of the cervical spine and patient demographics/presentation. Comprehensive craniospinal digital subtraction angiograms were evaluated to classify shunt location, type (arteriovenous malformation (AVM) vs arteriovenous fistula (AVF)), and presence of high-risk venous drainage. RESULTS: Some 52 lesions were identified and categorized as pial/dural/epidural/paravertebral AVFs and intramedullary/extraspinal AVMs. Lesions were classified as high risk or not depending on the presence of retrograde flow into at least one vein that directly drains the spinal cord or brain. All patients who presented with either hemorrhage or infarct had underlying high-risk lesions. Additionally, 50% (17/34) of symptomatic patients with high-risk lesions presented with neurological extremity symptoms (OR=10.0, p=0.037) most of which fit a myelopathic pattern. CONCLUSION: We present an updated classification system for shunting lesions of the spine that focuses on high-risk retrograde flow to the brain or spine in addition to anatomical location in order to better inform patient management.

Clot composition and recanalization outcomes in mechanical thrombectomy.

BACKGROUND: Mechanical thrombectomy (MT) has become standard for large vessel occlusions, but rates of complete recanalization are suboptimal. Previous reports correlated radiographic signs with clot composition and a better response to specific techniques. Therefore, understanding clot composition may allow improved outcomes. METHODS: Clinical, imaging, and clot data from patients enrolled in the STRIP Registry from September 2016 to September 2020 were analyzed. Samples were fixed in 10% phosphate-buffered formalin and stained with hematoxylin-eosin and Martius Scarlett Blue. Percent composition, richness, and gross appearance were evaluated. Outcome measures included the rate of first-pass effect (FPE, modified Thrombolysis in Cerebral Infarction 2c/3) and the number of passes. RESULTS: A total of 1430 patients of mean±SD age 68.4±13.5 years (median (IQR) baseline National Institutes of Health Stroke Scale score 17.2 (10.5-23), IV-tPA use 36%, stent-retrievers (SR) 27%, contact aspiration (CA) 27%, combined SR+CA 43%) were included. The median (IQR) number of passes was 1 (1-2). FPE was achieved in 39.3% of the cases. There was no association between percent histological composition or clot richness and FPE in the overall population. However, the combined technique resulted in lower FPE rates for red blood cell (RBC)-rich (P<0.0001), platelet-rich (P=0.003), and mixed (P<0.0001) clots. Fibrin-rich and platelet-rich clots required a higher number of passes than RBC-rich and mixed clots (median 2 and 1.5 vs 1, respectively; P=0.02). CA showed a trend towards a higher number of passes with fibrin-rich clots (2 vs 1; P=0.12). By gross appearance, mixed/heterogeneous clots had lower FPE rates than red and white clots. CONCLUSIONS: Despite the lack of correlation between clot histology and FPE, our study adds to the growing evidence supporting the notion that clot composition influences recanalization treatment strategy outcomes.

Revascularization of a Complex Case of Vertebrobasilar Insufficiency with Occipital Artery-Anterior Inferior Cerebellar Artery Bypass.

Atherosclerotic disease is the most common etiology in causing posterior circulation strokes and can be found within the intracranial vertebrobasilar system.1 Endovascular and surgical approaches to treat this disease have been defined with both advantages and disadvantages.2,3 We present a case of surgical revascularization of a complex case of vertebrobasilar insufficiency with occipital artery (OA)-anterior inferior cerebellar artery (AICA) bypass (Video 1). A 56-year-old gentleman presented with severe, disabling, and progressive symptoms of vertebrobasilar insufficiency refractory to maximal medical management. Symptom onset was 2 years prior after suffering a left lateral medullary stroke due to a left vertebral artery (VA) occlusion. Angiography showed left VA occlusion after the origin of the posterior inferior cerebellar artery (PICA) and a hypoplastic right VA mostly ending in a PICA with a small and critically stenosed branch to the basilar artery. An initial attempt to revascularize the chronic totally occluded left VA using a combination of anterograde and retrograde (via PComm) approaches was unsuccessful. The decision was made to proceed with an OA-AICA bypass. The end-to-side anastomosis was conducted in the right cerebellopontine cistern and was uncomplicated. Postoperative angiography demonstrated a patent bypass with brisk OA-to-AICA flow with retrograde filling of the basilar artery and its branches. No perioperative strokes. The patient remained free of recurrent symptoms of vertebrobasilar insufficiency at 6 months' follow-up.

Human "live cadaver" neurovascular model for proximal and distal mechanical thrombectomy in stroke.

BACKGROUND: Preclinical testing platforms that accurately replicate complex human cerebral vasculature are critical to advance neurointerventional knowledge, tools, and techniques. Here, we introduced and validated a human "live cadaveric" head-and-neck neurovascular model optimized for proximal and distal vascular occlusion and recanalization techniques. METHODS: Human cadaveric head-and-neck specimens were cannulated bilaterally in the jugular veins, carotid, and vertebral arteries. Specimens were then coupled with modular glass models of the aorta and extracranial carotid arteries, as well as radial and femoral access ports. Intracranial physiological flow was simulated using a flow-delivery system and blood-mimicking fluid. Baseline anatomy, histological, and mechanical properties of cerebral arteries were compared with those of fresh specimens. Radiopaque clot analogs were embolized to replicate proximal and distal arterial occlusions, followed by thrombectomy. Experienced interventionalists scored the model on different aspects. RESULTS: Compared with counterpart fresh human arteries, formalin-fixed arteries showed similar mechanical properties, including maximum stretch, increased tensile strength/stiffness, and friction coefficients were also not significantly different. On histology, minimal endothelial damage was noted in arteries after 3 months of light fixation, otherwise the arterial wall maintained the structural integrity. Contrast angiographies showed no micro- or macro-vasculature obstruction. Proximal and distal occlusions created within the middle cerebral arteries were consistently obtained and successfully recanalized. Additionally, interventionists scored the model highly realistic, indicating great similarity to patients' vasculature. CONCLUSIONS: The human "live cadaveric" neurovascular model accurately replicates the anatomy, mechanics, and hemodynamics of cerebral vasculature and allows the performance of neurointerventional procedures equivalent to those done in patients.

Correlation of von Willebrand factor and platelets with acute ischemic stroke etiology and revascularization outcome: an immunohistochemical study.

BACKGROUND: Platelets and von Willebrand factor (vWF) are key components of acute ischemic stroke (AIS) emboli. We aimed to investigate the CD42b (platelets)/vWF expression, its association with stroke etiology and the impact these components may have on the clinical/procedural parameters. METHODS: CD42b/vWF immunostaining was performed on 288 emboli collected as part of the multicenter STRIP Registry. CD42b/VWF expression and distribution were evaluated. Student's t-test and χ2 test were performed as appropriate. RESULTS: The mean CD42b and VWF content in clots was 44.3% and 21.9%, respectively. There was a positive correlation between platelets and vWF (r=0.64, p<0.001**). We found a significantly higher vWF level in the other determined etiology (p=0.016*) and cryptogenic (p=0.049*) groups compared with cardioembolic etiology. No significant difference in CD42b content was found across the etiology subtypes. CD42b/vWF patterns were significantly associated with stroke etiology (p=0.006*). The peripheral pattern was predominant in atherosclerotic clots (36.4%) while the clustering (patchy) pattern was significantly associated with cardioembolic and cryptogenic origin (66.7% and 49.8%, respectively). The clots corresponding to other determined etiology showed mainly a diffuse pattern (28.1%). Two types of platelets were distinguished within the CD42b-positive clusters in all emboli: vWF-positive platelets were observed at the center, surrounded by vWF-negative platelets. Thrombolysis correlated with a high platelet content (p=0.03*). vWF-poor and peripheral CD42b/vWF pattern correlated with first pass effect (p=0.03* and p=0.04*, respectively). CONCLUSIONS: The vWF level and CD42b/vWF distribution pattern in emboli were correlated with AIS etiology and revascularization outcome. Platelet content was associated with response to thrombolysis.

Evaluation of an in vivo preclinical model for human middle meningeal artery embolization using the posterior intercostal artery of the swine.

BACKGROUND: Embolization of the middle meningeal artery (MMA) is a promising minimally invasive technique that is gaining traction in the treatment of chronic subdural hematoma. Unfortunately, the human meninges and associated arteries are significantly larger than those of conventional laboratory animals, making the development of a clinically relevant animal model for testing of embolization agents elusive. OBJECTIVE: To introduce the posterior intercostal artery (PIA) model in swine and provide anatomical, angiographic, histological, and procedural data to validate its relevance in modeling the human MMA. METHODS: In human cadaveric specimens, 3D angiograms of the internal maxillary arteries (n=6) were obtained and the dura with MMA were harvested and histologically processed. Angiographic and histologic data of the human MMA were compared with the swine PIA (three animals). Then, embolization of the PIA (n=48 arteries) was conducted with liquid embolization agent (Onyx, Medtronic), and angiographic and histological results were assessed acutely (four animals) and after 30 days (two animals). RESULTS: The human MMA has equivalent diameter, length, branching pattern, 3D trajectory, and wall structure to those of swine PIAs. Each swine has 12 to 14 PIAs (6-7 per side) suitable for acute or chronic embolization, which can be performed with high fidelity using the same devices, agents, and techniques currently used to embolize the MMA. The arterial wall structure and the acute and chronic histological findings in PIAs after embolization are comparable to those of humans. CONCLUSIONS: This PIA model in swine could be used for research and development; objective benchmarking of agents, devices, and techniques; and in the training of neurointerventionalists.

Pituitary adenomas and cerebrovascular disease: A review on pathophysiology, prevalence, and treatment.

Pituitary adenomas (PAs) have been shown to cause excess cardiovascular disease comorbidity and mortality. Cerebrovascular disease (CeVD) is a small subset of cardiovascular disease with high morbidity, and its risk in patients with pituitary adenomas has been sparingly explored. In this review, we examine what is known about the prevalence of cerebrovascular disease in patients with PAs, from its initial discovery in 1970 to present. An abundance of literature describes increased cerebrovascular mortality in patients with acromegaly, while research on other PA subtypes is less frequent but shows a similarly elevated CeVD mortality relative to healthy populations. We also review how cerebrovascular risk changes after PAs are treated, with PA treatment appearing to prevent further accumulation of cerebrovascular risk without reversing prior elevations. While acromegaly-associated CeVD appears to be caused by elevated growth hormone (GH) levels and Cushing disease's elevated glucocorticoids similarly cause durable alterations in cerebrovascular structure and function, less is known about the mechanisms behind CeVD in other PA subpopulations. Proposed pathophysiologies include growth hormone deficiency inducing vessel wall damage or other hormone deficits causing increased atherosclerotic disease. Early diagnosis and treatment of PAs may be the key to minimizing lifetime CeVD risk elevations. More research is needed to better understand the mechanisms behind the increased CeVD seen in patients with PAs. Physicians caring for PA patients must remain vigilant for signs and symptoms of cerebrovascular disease in this patient population.

Bibliometric Trends in Open Surgical and Endovascular Cerebrovascular Research.

The last decade has witnessed a major expansion in endovascular interventions concurrent with a contraction of open neurovascular surgeries. Whether research efforts have also shifted from open to endovascular neurosurgery is an effect that has not been explored extensively. Understanding the bibliometric trend is important for researchers, funding agencies, and publishing journals. The aim of this review is to explore this potential shift. We compared the bibliometrics of open cerebrovascular and endovascular research articles published in two neurosurgical journals (Journal of Neurosurgery, Neurosurgery) and two neuroradiological journals (Journal of Neurointerventional Surgery, American Journal of Neuroradiology). Data were collected between September 26, 2021, and October 18, 2021. Articles published in 2011, 2013, 2015, 2017, and 2019 from the journals were screened. Neurovascular articles were classified into open surgical, endovascular, or mixed. Bibliometric parameters were collected via SCOPUS and journals' websites. A total of 8,018 articles were screened, of which 1,551 were included (16.2% open, 62.2% endovascular, 21.5% mixed). Most articles were related to aneurysms (76%). Open-access status correlated with increased citations (p<0.001) and Altmetric (p<0.001), which measures online activity. Comparing 2011 and 2019, the article distribution (open/endovascular/mixed) has changed significantly (χ2 test, p=0.002), with open articles dropping from 23.6% (68/288) to 12.9% (44/342) and endovascular articles rising from 56.6% (163/288) to 65.8% (225/342). Using the Kruskal-Wallis test, the citation distribution is different across the three groups in 2019 (p<0.001), favoring endovascular articles, but not in the other years. Our study suggests a trend of diminishing open neurovascular research output and increasing endovascular research output, in terms of both the number of articles and the citations. More time for citation accumulation may be required to verify this trend.

Intra-procedural cerebral sinus thrombosis during endovascular treatment of idiopathic intracranial hypertension.

Stenting of the intracranial venous sinuses has shown promising results in patients who are refractory to medical treatment of idiopathic intracranial hypertension (IIH). Among the reported complications associated with this procedure, in-stent thrombosis is an unreported one. We present a case of cerebral sinus thrombosis during endovascular treatment of IIH. A 33-year-old man with multiple comorbidities was presented with non-specific vision changes and headaches. Initial workup revealed a diagnosis of idiopathic intracranial hypertension which was treated medically but with no improvement. Therefore, cerebral sinus stenting was pursued. During the procedure, an in-stent thrombus was identified which was retrieved mechanically and was sent for histological and immunohistochemical evaluation. The retrieved thrombus was predominantly composed of RBCs (57.8%) followed by fibrin (30.78%), platelet (6.4%), and WBCs (5.95%), with high expression of CitH3 (neutrophil extra cellular traps specific marker) (10.9%), and CD66 (11.35%).

Clinical and imaging outcomes of cerebrospinal fluid-venous fistula embolization.

BACKGROUND: We report outcomes of spontaneous intracranial hypotension (SIH) patients who underwent transvenous embolization of cerebrospinal fluid-venous fistulas (CSFVFs) confirmed on digital subtraction myelography (DSM) performed at our institution. METHODS: This is a retrospective evaluation of a prospectively collected database of SIH patients who underwent transvenous embolization of CSFVFs. Only patients who had fistulas confirmed on DSM performed at our institution were included. All patients had a baseline MRI and an MRI performed at least 90 days post-embolization, as well as clinical evaluation using the six item Headache Impact Test (HIT-6) and the Patient Global Impression of Change (PGIC) scales. Paired t-test was used to report changes in Bern MRI scores and HIT-6 scores at follow-up. RESULTS: 40 patients were included (29 female, 11 male). Mean age was 57.4±10.3 years. Mean Bern score improved from 5.7±3.0 at baseline to 1.3±2.0 at follow-up (p<0.0001). Mean HIT-6 score at baseline was 67.2±11.1 and at follow-up was 41.5±10.1 (p<0.0001). Median PGIC was 1, with 36 patients (90.0%) reporting at least minimal improvement and 32 patients (82.5%) reporting much or very much improvement. Complications included persistent local site pain in 12 patients (30%), suspected rebound intracranial hypertension requiring medical intervention in 7 patients (17.5%), and asymptomatic tiny Onyx emboli to the lungs in 3 patients (7.5%). CONCLUSIONS: Transvenous embolization of CSFVFs using Onyx is safe and effective, resulting in significant improvement in headache and overall clinical outcomes in nearly 90% of patients, and substantial improvements in brain MRI abnormalities.

Histological evaluation of acute ischemic stroke thrombi may indicate the occurrence of vessel wall injury during mechanical thrombectomy.

BACKGROUND: Several animal studies have demonstrated that mechanical thrombectomy (MT) for acute ischemic stroke (AIS) may cause vessel wall injury (VWI). However, the histological changes in human cerebral arteries following MT are difficult to determine. OBJECTIVE: To investigate the occurrence of VWI during MT by histological and immunohistochemical evaluation of AIS clots. METHODS: As part of the multicenter STRIP registry, 277 clots from 237 patients were analyzed using Martius Scarlett Blue stain and immunohistochemistry for CD34 (endothelial cells) and smooth muscle actin (smooth muscle cells). RESULTS: MT devices used were aspiration catheters (100 cases), stentriever (101 cases), and both (36 cases). VWI was found in 33/277 clots (12%). There was no significant correlation between VWI and MT device. The degree of damage varied from grade I (mild intimal damage, 24 clots), to grade II (relevant intimal and subintimal damage, 3 clots), and III (severe injury, 6 clots). VWI clots contained significantly more erythrocytes (p=0.006*) and less platelets/other (p=0.005*) than non-VWI clots suggesting soft thrombus material.Thrombolysis correlated with a lower rate of VWI (p=0.04*). VWI cases showed a significantly higher number of passes (2 [1-4] vs 1 [1-3], p=0.028*) and poorer recanalization outcome (p=0.01*) than cases without VWI. CONCLUSIONS: Histological markers of VWI were present in 12% of AIS thrombi, suggesting that VWI might be related to MT. VWI was associated with soft thrombus consistency, higher number of passes and poorer revascularization outcome. There was no significant correlation between VWI and MT device.

Correlation between computed tomography angiography and histology of carotid artery atherosclerosis: Can semi-automated imaging software predict a plaque's composition?

BACKGROUND: Using computed tomography angiography to differentiate between components of carotid atherosclerotic lesions remains largely elusive. This study sought to validate a semi-automated software for computed tomography angiography plaque analysis using histologic comparisons. MATERIALS AND METHODS: A retrospective review was performed of consecutive patients that underwent a carotid endarterectomy, with pre-procedural computed tomography angiography imaging of the cervical arterial vasculature available for review. Images were evaluated using a commercially-available software package, which produced segmented analyses of intraplaque components (e.g. intraplaque hemorrhage, lipid-rich necrotic core, and calcifications). On imaging, each component was assessed in terms of its (1) presence or absence, and (2) both volume and proportion of the total plaque volume (if present). On histological evaluation of carotid endarterectomy specimens, each component was evaluated as an estimated proportion of total plaque volume. RESULTS: Of 80 included patients, 30 (37.5%) were female. The average age was 69.7 years (SD = 9.1). Based on imaging, intraplaque hemorrhage was the smallest contributor to plaque composition (1.2% of volumes on average). Statistically significant linear associations were noted between the proportion of intraplaque hemorrhage, lipid-rich necrotic core, and calcifications on histology and the volume of each component on imaging (p values ranged from 0.0008 to 0.01). Area under curve were poor for intraplaque hemorrhage and lipid-rich necrotic core (0.59 and 0.61, respectively) and acceptable for calcifications (0.73). CONCLUSION: Semi-automated analyses of computed tomography angiography have limited diagnostic accuracy in the detection of intraplaque hemorrhage and lipid-rich necrotic core in carotid artery plaques. However, volumetric imaging measurements of different components corresponded with histologic analysis.

Transvenous embolization of a cerebrospinal fluid-venous fistula for the treatment of spontaneous intracranial hypotension.

Cerebrospinal fluid-venous fistula is an increasingly recognized cause of spontaneous intracranial hypotension.1 The site of the leak is between the dural sleeve around a spinal nerve root and the surrounding foraminal veins. In appropriately investigated patients, transvenous embolization of the draining foraminal and paraspinal veins has been shown to be an effective way of treating the disease, with low periprocedural morbidity, improvement in symptoms and radiological appearances.2 Video 1 shows the technique employed in a typical case using Onyx (Medtronic, Minnesota, USA) to embolize a CSF-venous fistula at the right T10 neural foramen. neurintsurg;14/9/948/V1F1V1Video 1Video showing the technique for trans-venous embolization of a right T10 CSF-venous fistula for the treatment of spontaneous intracranial hypotension. The first section covers patient selection and work up, before then focusing on the technical aspects of navigating through the azygos system to the target foramen and completely occluding the pathway for CSF outflow.

Evaluation and treatment of headache associated with moyamoya disease - a narrative review.

BACKGROUND: Headache in patients with moyamoya disease is an under-addressed topic in the medical literature. Delay in the diagnosis of moyamoya disease or inappropriate treatment of headache could lead to devastating cerebrovascular outcome. With the evolving understanding of moyamoya disease, migraine pathophysiology, and various migraine-specific medications that have become available, it is crucial to provide an updated overview on this topic. METHODS: We searched PubMed for keywords including moyamoya disease, moyamoya syndrome, headache in moyamoya, surgical revascularization, surgical bypass, migraine and moyamoya, and calcitonin gene-related peptide (CGRP). We summarized the literature and provide a comprehensive review of the headache presentation, possible mechanisms, the impact of various surgical revascularizations on headache in patients with moyamoya disease, and the medical management of headache incorporating novel migraine-specific treatments.Results and conclusion: The most common headache phenotype is migraine; tension-type headache, hemiplegic migraine, and cluster headache have also been reported. Most patients experience improvement of headache after surgical revascularization, though some patients report worsening, or new-onset headache after surgery. Given the complexity of moyamoya disease, careful consideration of different types of medical therapy for headache is necessary to improve the quality of life while not increasing the risk of adverse cerebrovascular events. More prospective studies are warranted to better understand and manage headache in patients with moyamoya disease.

Quantification of clot spatial heterogeneity and its impact on thrombectomy.

BACKGROUND: Compositional and structural features of retrieved clots by thrombectomy can provide insight into improving the endovascular treatment of ischemic stroke. Currently, histological analysis is limited to quantification of compositions and qualitative description of the clot structure. We hypothesized that heterogeneous clots would be prone to poorer recanalization rates and performed a quantitative analysis to test this hypothesis. METHODS: We collected and did histology on clots retrieved by mechanical thrombectomy from 157 stroke cases (107 achieved first-pass effect (FPE) and 50 did not). Using an in-house algorithm, the scanned images were divided into grids (with sizes of 0.2, 0.3, 0.4, 0.5, and 0.6 mm) and the extent of non-uniformity of RBC distribution was computed using the proposed spatial heterogeneity index (SHI). Finally, we validated the clinical significance of clot heterogeneity using the Mann-Whitney test and an artificial neural network (ANN) model. RESULTS: For cases with FPE, SHI values were smaller (0.033 vs 0.039 for grid size of 0.4 mm, P=0.028) compared with those without. In comparison, the clot composition was not statistically different between those two groups. From the ANN model, clot heterogeneity was the most important factor, followed by fibrin content, thrombectomy techniques, red blood cell content, clot area, platelet content, etiology, and admission of intravenous tissue plasminogen activator (IV-tPA). No statistical difference of clot heterogeneity was found for different etiologies, thrombectomy techniques, and IV-tPA administration. CONCLUSIONS: Clot heterogeneity can affect the clot response to thrombectomy devices and is associated with lower FPE. SHI can be a useful metric to quantify clot heterogeneity.

Association between clot composition and stroke origin in mechanical thrombectomy patients: analysis of the Stroke Thromboembolism Registry of Imaging and Pathology.

BACKGROUND: We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients to study the association between histological composition and stroke etiology METHODS: Consecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using martius scarlet blue (MSB) staining, and quantification for red blood cells (RBCs), white blood cells (WBCs), fibrin and platelets was performed using Orbit Image Software. A Wilcoxon test was used for continuous variables and χ2 test for categorical variables. RESULTS: 1350 patients were included in this study. The overall rate of Thrombolysis In Cerebral Infarction (TICI) 2c/3 was 68%. 501 patients received tissue plasminogen activator (tPA) (37%). 267 patients (20%) had a large artery atherosclerosis (LAA) source, 662 (49%) a cardioembolic (CE) source, 301 (22%) were cryptogenic, and the remainder had other identifiable sources including hypercoagulable state or dissection. LAA thrombi had a higher mean RBC density (46±23% vs 42±22%, p=0.01) and a lower platelet density (24±18% vs 27±18%, p=0.03) than CE thrombi. Clots from dissection patients had the highest mean RBC density (50±24%) while clots from patients with a hypercoagulable state had the lowest mean RBC density (26±21%). CONCLUSIONS: Our study found statistically significant but clinically insignificant differences between clots of CE and LAA etiologies. Future studies should emphasize molecular, proteomic and immunohistochemical characteristics to determine links between clot composition and etiology.