Trial of Early Minimally Invasive Removal of Intracerebral Hemorrhage.

BACKGROUND: Trials of surgical evacuation of supratentorial intracerebral hemorrhages have generally shown no functional benefit. Whether early minimally invasive surgical removal would result in better outcomes than medical management is not known. METHODS: In this multicenter, randomized trial involving patients with an acute intracerebral hemorrhage, we assessed surgical removal of the hematoma as compared with medical management. Patients who had a lobar or anterior basal ganglia hemorrhage with a hematoma volume of 30 to 80 ml were assigned, in a 1:1 ratio, within 24 hours after the time that they were last known to be well, to minimally invasive surgical removal of the hematoma plus guideline-based medical management (surgery group) or to guideline-based medical management alone (control group). The primary efficacy end point was the mean score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes, according to patients' assessment) at 180 days, with a prespecified threshold for posterior probability of superiority of 0.975 or higher. The trial included rules for adaptation of enrollment criteria on the basis of hemorrhage location. A primary safety end point was death within 30 days after enrollment. RESULTS: A total of 300 patients were enrolled, of whom 30.7% had anterior basal ganglia hemorrhages and 69.3% had lobar hemorrhages. After 175 patients had been enrolled, an adaptation rule was triggered, and only persons with lobar hemorrhages were enrolled. The mean score on the utility-weighted modified Rankin scale at 180 days was 0.458 in the surgery group and 0.374 in the control group (difference, 0.084; 95% Bayesian credible interval, 0.005 to 0.163; posterior probability of superiority of surgery, 0.981). The mean between-group difference was 0.127 (95% Bayesian credible interval, 0.035 to 0.219) among patients with lobar hemorrhages and -0.013 (95% Bayesian credible interval, -0.147 to 0.116) among those with anterior basal ganglia hemorrhages. The percentage of patients who had died by 30 days was 9.3% in the surgery group and 18.0% in the control group. Five patients (3.3%) in the surgery group had postoperative rebleeding and neurologic deterioration. CONCLUSIONS: Among patients in whom surgery could be performed within 24 hours after an acute intracerebral hemorrhage, minimally invasive hematoma evacuation resulted in better functional outcomes at 180 days than those with guideline-based medical management. The effect of surgery appeared to be attributable to intervention for lobar hemorrhages. (Funded by Nico; ENRICH ClinicalTrials.gov number, NCT02880878.).

Diffusion-Weighted Imaging Fluid-Attenuated Inversion Recovery Mismatch on Portable, Low-Field Magnetic Resonance Imaging Among Acute Stroke Patients.

OBJECTIVE: For stroke patients with unknown time of onset, mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) can guide thrombolytic intervention. However, access to MRI for hyperacute stroke is limited. Here, we sought to evaluate whether a portable, low-field (LF)-MRI scanner can identify DWI-FLAIR mismatch in acute ischemic stroke. METHODS: Eligible patients with a diagnosis of acute ischemic stroke underwent LF-MRI acquisition on a 0.064-T scanner within 24 h of last known well. Qualitative and quantitative metrics were evaluated. Two trained assessors determined the visibility of stroke lesions on LF-FLAIR. An image coregistration pipeline was developed, and the LF-FLAIR signal intensity ratio (SIR) was derived. RESULTS: The study included 71 patients aged 71 ± 14 years and a National Institutes of Health Stroke Scale of 6 (interquartile range 3-14). The interobserver agreement for identifying visible FLAIR hyperintensities was high (κ = 0.85, 95% CI 0.70-0.99). Visual DWI-FLAIR mismatch had a 60% sensitivity and 82% specificity for stroke patients <4.5 h, with a negative predictive value of 93%. LF-FLAIR SIR had a mean value of 1.18 ± 0.18 <4.5 h, 1.24 ± 0.39 4.5-6 h, and 1.40 ± 0.23 >6 h of stroke onset. The optimal cut-point for LF-FLAIR SIR was 1.15, with 85% sensitivity and 70% specificity. A cut-point of 6.6 h was established for a FLAIR SIR <1.15, with an 89% sensitivity and 62% specificity. INTERPRETATION: A 0.064-T portable LF-MRI can identify DWI-FLAIR mismatch among patients with acute ischemic stroke. Future research is needed to prospectively validate thresholds and evaluate a role of LF-MRI in guiding thrombolysis among stroke patients with uncertain time of onset. ANN NEUROL 2024;96:321-331.

ARISE I Consensus Statement on the Management of Chronic Subdural Hematoma.

ARISE (Aneurysm/AVM/cSDH Roundtable Discussion With Industry and Stroke Experts) organized a one-and-a-half day meeting and workshop and brought together representatives from academia, industry, and government to discuss the most promising approaches to improve outcomes for patients with chronic subdural hematoma (cSDH). The emerging role of middle meningeal artery embolization in clinical practice and the design of current and potential future trials were the primary focuses of discussion. Existing evidence for imaging, indications, agents, and techniques was reviewed, and areas of priority for study and key questions surrounding the development of new and existing treatments for cSDH were identified. Multiple randomized, controlled trials have met their primary efficacy end points, providing high-level evidence that middle meningeal artery embolization is a potent adjunctive therapy to the standard (surgical and nonsurgical) management of neurologically stable cSDH patients in terms of reducing rates of disease recurrence. Pooled data analyses following the formal conclusion and publication of these trials will form a robust foundation upon which guidelines can be strengthened for cSDH treatment modalities and optimal patient selection, as well as delineate future lines of investigation.

Future of Endovascular and Surgical Treatments of Atherosclerotic Intracranial Stenosis.

Intracranial atherosclerotic disease and resultant intracranial stenosis is a global leading cause of stroke, and poses an ongoing treatment challenge. Among patients with intracranial stenosis, those with hemodynamic compromise are at high risk for recurrent stroke despite medical therapy and risk factor modification. Revascularization of the hypoperfused territory is the most plausible treatment strategy for these high-risk patients, yet surgical and endovascular therapies have not yet shown to be sufficiently safe and effective in randomized controlled trials. Advances in diagnostic and therapeutic technologies have led to a resurgence of interest in surgical and endovascular treatment strategies, with a growing body of evidence to support their further evaluation in the treatment of select patient populations. This review outlines the current and emerging endovascular and surgical treatments and highlights promising future management strategies.

Most Promising Approaches to Improve Brain AVM Management: ARISE I Consensus Recommendations.

Brain arteriovenous malformations (bAVMs) are complex, and rare arteriovenous shunts that present with a wide range of signs and symptoms, with intracerebral hemorrhage being the most severe. Despite prior societal position statements, there is no consensus on the management of these lesions. ARISE (Aneurysm/bAVM/cSDH Roundtable Discussion With Industry and Stroke Experts) was convened to discuss evidence-based approaches and enhance our understanding of these complex lesions. ARISE identified the need to develop scales to predict the risk of rupture of bAVMs, and the use of common data elements to perform prospective registries and clinical studies. Additionally, the group underscored the need for comprehensive patient management with specialized centers with expertise in cranial and spinal microsurgery, neurological endovascular surgery, and stereotactic radiosurgery. The collection of prospective multicenter data and gross specimens was deemed essential for improving bAVM characterization, genetic evaluation, and phenotyping. Finally, bAVMs should be managed within a multidisciplinary framework, with clinical studies and research conducted collaboratively across multiple centers, harnessing the collective expertise and centralization of resources.

Direct Versus Indirect Revascularization for Moyamoya: a Large Multicenter Study.

BACKGROUND: Moyamoya is a chronic occlusive cerebrovascular disease of unknown etiology causing neovascularization of the lenticulostriate collaterals at the base of the brain. Although revascularization surgery is the most effective treatment for moyamoya, there is still no consensus on the best surgical treatment modality as different studies provide different outcomes. OBJECTIVE: In this large case series, we compare the outcomes of direct (DR) and indirect revascularisation (IR) and compare our results to the literature in order to reflect on the best revascularization modality for moyamoya. METHODS: We conducted a multicenter retrospective study in accordance with the Strengthening the Reporting of Observational studies in Epidemiology guidelines of moyamoya affected hemispheres treated with DR and IR surgeries across 13 academic institutions predominantly in North America. All patients who underwent surgical revascularization of their moyamoya-affected hemispheres were included in the study. The primary outcome of the study was the rate of symptomatic strokes. RESULTS: The rates of symptomatic strokes across 515 disease-affected hemispheres were comparable between the two cohorts (11.6% in the DR cohort vs 9.6% in the IR cohort, OR 1.238 (95% CI 0.651 to 2.354), p=0.514). The rate of total perioperative strokes was slightly higher in the DR cohort (6.1% for DR vs 2.0% for IR, OR 3.129 (95% CI 0.991 to 9.875), p=0.052). The rate of total follow-up strokes was slightly higher in the IR cohort (8.1% vs 6.6%, OR 0.799 (95% CI 0.374 to 1.709) p=0.563). CONCLUSION: Since both modalities showed comparable rates of overall total strokes, both modalities of revascularization can be performed depending on the patient's risk assessment.

Automated ASPECTS calculation may equal the performance of experienced clinicians: a machine learning study based on a large cohort.

OBJECTIVES: The Alberta Stroke Program Early CT Score (ASPECTS) is a semi-quantitative method to evaluate the severity of early ischemic change on non-contrast computed tomography (NCCT) in patients with acute ischemic stroke (AIS). In this work, we propose an automated ASPECTS method based on large cohort of data and machine learning. METHODS: For this study, we collected 3626 NCCT cases from multiple centers and annotated directly on this dataset by neurologists. Based on image analysis and machine learning methods, we constructed a two-stage machine learning model. The validity and reliability of this automated ASPECTS method were tested on an independent external validation set of 300 cases. Statistical analyses on the total ASPECTS, dichotomized ASPECTS, and region-level ASPECTS were presented. RESULTS: On an independent external validation set of 300 cases, for the total ASPECTS results, the intraclass correlation coefficient between automated ASPECTS and expert-rated was 0.842. The agreement between ASPECTS threshold of ≥ 6 versus < 6 using a dichotomized method was moderate (κ = 0.438, 0.391-0.477), and the detection rate (sensitivity) was 86.5% for patients with ASPECTS threshold of ≥ 6. Compared with the results of previous studies, our method achieved a slight lead in sensitivity (67.8%) and AUC (0.845), with comparable accuracy (78.9%) and specificity (81.2%). CONCLUSION: The proposed automated ASPECTS method driven by a large cohort of NCCT images performed equally well compared with expert-rated ASPECTS. This work further demonstrates the validity and reliability of automated ASPECTS evaluation method. CLINICAL RELEVANCE STATEMENT: The automated ASPECTS method proposed by this study may help AIS patients to receive rapid intervention, but should not be used as a stand-alone diagnostic basis. KEY POINTS: NCCT-based manual ASPECTS scores were poorly consistent. Machine learning can automate the ASPECTS scoring process. Machine learning model design based on large cohort data can effectively improve the consistency of ASPECTS scores.

The impact of hypertension on clinical outcomes in moyamoya disease: a multicenter, propensity score-matched analysis.

BACKGROUND: Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive steno-occlusive changes in the internal carotid arteries, leading to an abnormal vascular network. Hypertension is prevalent among MMD patients, raising concerns about its impact on disease outcomes. This study aims to compare the clinical characteristics and outcomes of MMD patients with and without hypertension. METHODS: We conducted a multicenter, retrospective study involving 598 MMD patients who underwent surgical revascularization across 13 academic institutions in North America. Patients were categorized into hypertensive (n=292) and non-hypertensive (n=306) cohorts. Propensity score matching (PSM) was performed to adjust for baseline differences. RESULTS: The mean age was higher in the hypertension group (46 years vs. 36.8 years, p < 0.001). Hypertensive patients had higher rates of diabetes mellitus (45.2% vs. 10.7%, p < 0.001) and smoking (48.8% vs. 27.1%, p < 0.001). Symptomatic stroke rates were higher in the hypertension group (16% vs. 7.1%; OR: 2.48; 95% CI: 1.39-4.40, p = 0.002) before matching. After PSM, there were no significant differences in symptomatic stroke rates (11.1% vs. 7.7%; OR: 1.5; CI: 0.64-3.47, p = 0.34), perioperative strokes (6.2% vs. 2.1%; OR 3.13; 95% CI: 0.83-11.82, p = 0.09), or good functional outcomes at discharge (93% vs. 92.3%; OR 1.1; 95% CI: 0.45-2.69, p = 0.82). CONCLUSION: No significant differences in symptomatic stroke rates, perioperative strokes, or functional outcomes were observed between hypertensive and non-hypertensive Moyamoya patients. Appropriate management can lead to similar outcomes in both groups. Further prospective studies are required to validate these findings.

Complex intracranial aneurysms: a DELPHI study to define associated characteristics.

PURPOSE: Intracranial aneurysms present significant health risks, as their rupture leads to subarachnoid haemorrhage, which in turn has high morbidity and mortality rates. There are several elements affecting the complexity of an intracranial aneurysm. However, criteria for defining a complex intracranial aneurysm (CIA) in open surgery and endovascular treatment could differ, and actually there is no consensus on the definition of a "complex" aneurysm. This DELPHI study aims to assess consensus on variables defining a CIA. METHODS: An international panel of 50 members, representing various specialties, was recruited to define CIAs through a three-round Delphi process. The panelists participated in surveys with Likert scale responses and open-ended questions. Consensus criteria were established to determine CIA variables, and statistical analysis evaluated consensus and stability. RESULTS: In open surgery, CIAs were defined by fusiform or blister-like shape, dissecting aetiology, giant size (≥ 25 mm), broad neck encasing parent arteries, extensive neck surface, wall calcification, intraluminal thrombus, collateral branch from the sac, location (AICA, SCA, basilar), vasospasm context, and planned bypass (EC-IC or IC-IC). For endovascular treatment, CIAs included giant size, very wide neck (dome/neck ratio ≤ 1:1), and collateral branch from the sac. CONCLUSIONS: The definition of aneurysm complexity varies by treatment modality. Since elements related to complexity differ between open surgery and endovascular treatment, these consensus criteria of CIAs could even guide in selecting the best treatment approach.

Thrombectomy for Stroke With Large Infarct on Noncontrast CT: The TESLA Randomized Clinical Trial.

Importance: Recent large infarct thrombectomy trials used heterogeneous imaging modalities and time windows for patient selection. Noncontrast computed tomographic (CT) scan is the most common stroke imaging approach. It remains uncertain whether thrombectomy is effective for patients with large infarcts identified using noncontrast CT alone within 24 hours of stroke onset. Objective: To evaluate the effect of thrombectomy in patients with a large infarct on a noncontrast CT scan within 24 hours of onset. Design, Setting, and Participants: Open-label, blinded-end point, bayesian-adaptive randomized trial with interim analyses for early stopping (futility or success) or population enrichment, which was conducted at 47 US academic and community-based stroke thrombectomy centers. Three hundred patients presenting within 24 hours with anterior-circulation, large-vessel occlusion and large infarct on noncontrast CT scan, with Alberta Stroke Program Early CT Scores of 2 to 5, were randomized to undergo thrombectomy or usual care. Enrollment occurred July 16, 2019 to October 17, 2022; final follow-up, January 25, 2023. Intervention: The intervention patients (n = 152) underwent endovascular treatment using standard thrombectomy devices and usual medical care. Control patients (n = 148) underwent usual medical care alone. Main Outcomes and Measures: The primary efficacy end point was improvement in 90-day functional outcome measured using mean utility-weighted modified Rankin Scale (UW-mRS) scores (range, 0 [death or severe disability] to 10 [no symptoms]; minimum clinically important difference, 0.3). A bayesian model determined the posterior probability that the intervention would be superior to usual care; statistical significance was a 1-sided posterior probability of .975 or more. The primary adverse event end point was 90-day mortality; secondary adverse event end points included symptomatic intracranial hemorrhage and radiographic intracranial hemorrhage. Results: The trial enrolled 300 patients (152 intervention, 148 control; 138 females [46%]; median age, 67 years), without early stopping or enrichment; 297 patients completed the 90-day follow-up. The mean (SD) 90-day UW-mRS score was 2.93 (3.39) for the intervention group vs 2.27 (2.98) for the control group with an adjusted difference of 0.63 (95% credible interval [CrI], -0.09 to 1.34; posterior probability for superiority of thrombectomy, .96). The 90-day mortality was similar between groups: 35.3% (53 of 150) for the intervention group vs 33.3% (49 of 147) for the control group. Six of 151 patients (4.0%) in the intervention group and 2 of 149 (1.3%) in the control group experienced 24-hour symptomatic intracranial hemorrhage. Fourteen patients of 148 (9.5%) in the intervention group vs 4 of 146 (2.7%) in the control group experienced parenchymal hematoma type 1 hemorrhages; 14 (9.5%) in the intervention group vs 5 (3.4%) in the control group experienced parenchymal hematoma type 2 hemorrhages; and 24 (16.2%) in the intervention group vs 9 (6.2%) in the control group experienced subarachnoid hemorrhages. Conclusions and Relevance: Among patients with a large infarct on noncontrast CT within 24 hours, thrombectomy did not demonstrate improvement in functional outcomes. But the width of the credible interval around the effect estimate includes the possibility of both no important effect and a clinically relevant benefit, so the potential role of thrombectomy with this imaging approach and time window will likely require additional study. Trial Registration: ClinicalTrials.gov Identifier: NCT03805308.

Endovascular Versus Medical Management of Posterior Cerebral Artery Occlusion Stroke: The PLATO Study.

BACKGROUND: The optimal management of patients with isolated posterior cerebral artery occlusion is uncertain. We compared clinical outcomes for endovascular therapy (EVT) versus medical management (MM) in patients with isolated posterior cerebral artery occlusion. METHODS: This multinational case-control study conducted at 27 sites in Europe and North America included consecutive patients with isolated posterior cerebral artery occlusion presenting within 24 hours of time last well from January 2015 to August 2022. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The coprimary outcomes were the 90-day modified Rankin Scale ordinal shift and ≥2-point decrease in the National Institutes of Health Stroke Scale. RESULTS: Of 1023 patients, 589 (57.6%) were male with median (interquartile range) age of 74 (64-82) years. The median (interquartile range) National Institutes of Health Stroke Scale was 6 (3-10). The occlusion segments were P1 (41.2%), P2 (49.2%), and P3 (7.1%). Overall, intravenous thrombolysis was administered in 43% and EVT in 37%. There was no difference between the EVT and MM groups in the 90-day modified Rankin Scale shift (aOR, 1.13 [95% CI, 0.85-1.50]; P=0.41). There were higher odds of a decrease in the National Institutes of Health Stroke Scale by ≥2 points with EVT (aOR, 1.84 [95% CI, 1.35-2.52]; P=0.0001). Compared with MM, EVT was associated with a higher likelihood of excellent outcome (aOR, 1.50 [95% CI, 1.07-2.09]; P=0.018), complete vision recovery, and similar rates of functional independence (modified Rankin Scale score, 0-2), despite a higher rate of SICH and mortality (symptomatic intracranial hemorrhage, 6.2% versus 1.7%; P=0.0001; mortality, 10.1% versus 5.0%; P=0.002). CONCLUSIONS: In patients with isolated posterior cerebral artery occlusion, EVT was associated with similar odds of disability by ordinal modified Rankin Scale, higher odds of early National Institutes of Health stroke scale improvement, and complete vision recovery compared with MM. There was a higher likelihood of excellent outcome in the EVT group despite a higher rate of symptomatic intracranial hemorrhage and mortality. Continued enrollment into ongoing distal vessel occlusion randomized trials is warranted.

Thrombectomy for anterior circulation stroke beyond 6 h from time last known well (AURORA): a systematic review and individual patient data meta-analysis.

BACKGROUND: Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis. METHODS: We did a systematic review and individual patient data meta-analysis between Jan 1, 2010, and March 1, 2021, of randomised controlled trials of endovascular stroke therapy. In the Analysis Of Pooled Data From Randomized Studies Of Thrombectomy More Than 6 Hours After Last Known Well (AURORA) collaboration, the primary outcome was disability on the modified Rankin Scale (mRS) at 90 days, analysed by ordinal logistic regression. Key safety outcomes were symptomatic intracerebral haemorrhage and mortality within 90 days. FINDINGS: Patient level data from 505 individuals (n=266 intervention, n=239 control; mean age 68·6 years [SD 13·7], 259 [51·3%] women) were included from six trials that met inclusion criteria of 17 screened published randomised trials. Primary outcome analysis showed a benefit of thrombectomy with an unadjusted common odds ratio (OR) of 2·42 (95% CI 1·76-3·33; p<0·0001) and an adjusted common OR (for age, gender, baseline stroke severity, extent of infarction on baseline head CT, and time from onset to random assignment) of 2·54 (1·83-3·54; p<0·0001). Thrombectomy was associated with higher rates of independence in activities of daily living (mRS 0-2) than best medical therapy alone (122 [45·9%] of 266 vs 46 [19·3%] of 238; p<0·0001). No significant difference between intervention and control groups was found when analysing either 90-day mortality (44 [16·5%] of 266 vs 46 [19·3%] of 238) or symptomatic intracerebral haemorrhage (14 [5·3%] of 266 vs eight [3·3%] of 239). No heterogeneity of treatment effect was noted across subgroups defined by age, gender, baseline stroke severity, vessel occlusion site, baseline Alberta Stroke Program Early CT Score, and mode of presentation; treatment effect was stronger in patients randomly assigned within 12-24 h (common OR 5·86 [95% CI 3·14-10·94]) than those randomly assigned within 6-12 h (1·76 [1·18-2·62]; pinteraction=0·0087). INTERPRETATION: These findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6-24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6-24 h time window. FUNDING: Stryker Neurovascular.

Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: Predictors of Clinical and Radiographic Failure from 636 Embolizations.

Background Knowledge regarding predictors of clinical and radiographic failures of middle meningeal artery (MMA) embolization (MMAE) treatment for chronic subdural hematoma (CSDH) is limited. Purpose To identify predictors of MMAE treatment failure for CSDH. Materials and Methods In this retrospective study, consecutive patients who underwent MMAE for CSDH from February 2018 to April 2022 at 13 U.S. centers were included. Clinical failure was defined as hematoma reaccumulation and/or neurologic deterioration requiring rescue surgery. Radiographic failure was defined as a maximal hematoma thickness reduction less than 50% at last imaging (minimum 2 weeks of head CT follow-up). Multivariable logistic regression models were constructed to identify independent failure predictors, controlling for age, sex, concurrent surgical evacuation, midline shift, hematoma thickness, and pretreatment baseline antiplatelet and anticoagulation therapy. Results Overall, 530 patients (mean age, 71.9 years ± 12.8 [SD]; 386 men; 106 with bilateral lesions) underwent 636 MMAE procedures. At presentation, the median CSDH thickness was 15 mm and 31.3% (166 of 530) and 21.7% (115 of 530) of patients were receiving antiplatelet and anticoagulation medications, respectively. Clinical failure occurred in 36 of 530 patients (6.8%, over a median follow-up of 4.1 months) and radiographic failure occurred in 26.3% (137 of 522) of procedures. At multivariable analysis, independent predictors of clinical failure were pretreatment anticoagulation therapy (odds ratio [OR], 3.23; P = .007) and an MMA diameter less than 1.5 mm (OR, 2.52; P = .027), while liquid embolic agents were associated with nonfailure (OR, 0.32; P = .011). For radiographic failure, female sex (OR, 0.36; P = .001), concurrent surgical evacuation (OR, 0.43; P = .009), and a longer imaging follow-up time were associated with nonfailure. Conversely, MMA diameter less than 1.5 mm (OR, 1.7; P = .044), midline shift (OR, 1.1; P = .02), and superselective MMA catheterization (without targeting the main MMA trunk) (OR, 2; P = .029) were associated with radiographic failure. Sensitivity analyses retained these associations. Conclusion Multiple independent predictors of failure of MMAE treatment for chronic subdural hematomas were identified, with small diameter (<1.5 mm) being the only factor independently associated with both clinical and radiographic failures. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Chaudhary and Gemmete in this issue.

A molecular modelling approach for identifying antiviral selenium-containing heterocyclic compounds that inhibit the main protease of SARS-CoV-2: an in silico investigation.

Coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic by the World Health Organization, and the situation worsens daily, associated with acute increases in case fatality rates. The main protease (Mpro) enzyme produced by SARS-CoV-2 was recently demonstrated to be responsible for not only viral reproduction but also impeding host immune responses. The element selenium (Se) plays a vital role in immune functions, both directly and indirectly. Thus, we hypothesised that Se-containing heterocyclic compounds might curb the activity of SARS-CoV-2 Mpro. We performed a molecular docking analysis and found that several of the selected selenocompounds showed potential binding affinities for SARS-CoV-2 Mpro, especially ethaselen (49), which exhibited a docking score of -6.7 kcal/mol compared with the -6.5 kcal/mol score for GC376 (positive control). Drug-likeness calculations suggested that these compounds are biologically active and possess the characteristics of ideal drug candidates. Based on the binding affinity and drug-likeness results, we selected the 16 most effective selenocompounds as potential anti-COVID-19 drug candidates. We also validated the structural integrity and stability of the drug candidate through molecular dynamics simulation. Using further in vitro and in vivo experiments, we believe that the targeted compound identified in this study (ethaselen) could pave the way for the development of prospective drugs to combat SARS-CoV-2 infections and trigger specific host immune responses.

Histologically interpretable clot radiomic features predict treatment outcomes of mechanical thrombectomy for ischemic stroke.

PURPOSE: Radiomics features (RFs) extracted from CT images may provide valuable information on the biological structure of ischemic stroke blood clots and mechanical thrombectomy outcome. Here, we aimed to identify RFs predictive of thrombectomy outcomes and use clot histomics to explore the biology and structure related to these RFs. METHODS: We extracted 293 RFs from co-registered non-contrast CT and CTA. RFs predictive of revascularization outcomes defined by first-pass effect (FPE, near to complete clot removal in one thrombectomy pass), were selected. We then trained and cross-validated a balanced logistic regression model fivefold, to assess the RFs in outcome prediction. On a subset of cases, we performed digital histopathology on the clots and computed 227 histomic features from their whole slide images as a means to interpret the biology behind significant RF. RESULTS: We identified 6 significantly-associated RFs. RFs reflective of continuity in lower intensities, scattered higher intensities, and intensities with abrupt changes in texture were associated with successful revascularization outcome. For FPE prediction, the multi-variate model had high performance, with AUC = 0.832 ± 0.031 and accuracy = 0.760 ± 0.059 in training, and AUC = 0.787 ± 0.115 and accuracy = 0.787 ± 0.127 in cross-validation testing. Each of the 6 RFs was related to clot component organization in terms of red blood cell and fibrin/platelet distribution. Clots with more diversity of components, with varying sizes of red blood cells and fibrin/platelet regions in the section, were associated with RFs predictive of FPE. CONCLUSION: Upon future validation in larger datasets, clot RFs on CT imaging are potential candidate markers for FPE prediction.

Evaluating a 3D deep learning pipeline for cerebral vessel and intracranial aneurysm segmentation from computed tomography angiography-digital subtraction angiography image pairs.

OBJECTIVE: Computed tomography angiography (CTA) is the most widely used imaging modality for intracranial aneurysm (IA) management, yet it remains inferior to digital subtraction angiography (DSA) for IA detection, particularly of small IAs in the cavernous carotid region. The authors evaluated a deep learning pipeline for segmentation of vessels and IAs from CTA using coregistered, segmented DSA images as ground truth. METHODS: Using 50 paired CTA-DSA images, the authors trained (n = 27), validated (n = 3), and tested (n = 20) a deep learning model (3D DeepMedic) for cerebrovasculature segmentation from CTA. A landmark-based coregistration algorithm was used for registration and upsampling of CTA images to paired DSA images. Segmented vessels from the DSA were used as the ground truth. Accuracy of the model for vessel segmentation was evaluated using conventional metrics (dice similarity coefficient [DSC]) and vessel segmentation-specific metrics, like connectivity-area-length (CAL). On the test cases (20 IAs), 3 expert raters attempted to detect and segment IAs. For each rater, the authors recorded the rate of IA detection, and for detected IAs, raters segmented and calculated important IA morphology parameters to quantify the differences in IA segmentation by raters to segmentations by DeepMedic. The agreement between raters, DeepMedic, and ground truth was assessed using Krippendorf's alpha. RESULTS: In testing, the DeepMedic model yielded a CAL of 0.971 ± 0.007 and a DSC of 0.868 ± 0.008. The model prediction delineated all IAs and resulted in average error rates of < 10% for all IA morphometrics. Conversely, average IA detection accuracy by the raters was 0.653 (undetected IAs were present to a significantly greater degree on the ICA, likely due to those in the cavernous region, and were significantly smaller). Error rates for IA morphometrics in rater-segmented cases were significantly higher than in DeepMedic-segmented cases, particularly for neck (p = 0.003) and surface area (p = 0.04). For IA morphology, agreement between the raters was acceptable for most metrics, except for the undulation index (α = 0.36) and the nonsphericity index (α = 0.69). Agreement between DeepMedic and ground truth was consistently higher compared with that between expert raters and ground truth. CONCLUSIONS: This CTA segmentation network (DeepMedic trained on DSA-segmented vessels) provides a high-fidelity solution for CTA vessel segmentation, particularly for vessels and IAs in the carotid cavernous region.

The first decade of flow diversion for intracranial aneurysms with the Pipeline embolization device.

OBJECTIVE: Flow diverter devices have revolutionized the treatment of intracranial aneurysms (IAs) since their approval in 2011 and have continued to evolve. The devices have been widely adopted across institutions and centers over the past decade; however, long-term follow-up after treatment with the Pipeline embolization device (PED) is not well described in the literature. The authors' institution was among the first to begin using PEDs, allowing them to report their series of patients treated with flow diverters ≥ 10 years ago. In this study, the authors aimed to evaluate the long-term angiographic and clinical outcomes of these patients and review lessons learned along the way. METHODS: The authors performed a retrospective review of their institution's IA database from January 2007 to July 2012. All patients with IAs treated with a PED prior to July 2012 were included. Clinical and angiographic characteristics were extracted. Available angiographic follow-up at 1, 3, 5, and 10 years was reported. RESULTS: A total of 83 patients with 92 aneurysms treated with a PED ≥ 10 years ago were identified and included in the study. The mean aneurysm dome diameter was 9.2 (SD 5.7) mm, the mean aneurysm height was 10.4 (SD 6.8) mm, and the mean neck width was 4.1 (SD 2.4) mm. Only 1 (1.1%) aneurysm was ruptured at presentation. Eight (8.7%) aneurysms were recurrences of previous treatment modalities. The morphology was saccular in 77 (83.7%) aneurysms, fusiform in 14 (15.2%), and blister-like in 1 (1.1%). Among saccular aneurysms, 60 (77.9%) were wide-necked. Seventy-five (81.5%) aneurysms were in the internal carotid artery, 12 (13.0%) were vertebrobasilar, 3 (3.3%) were in the middle cerebral artery, and 2 (2.2%) were in the posterior cerebral artery. Angiographic follow-up at 1, 3, 5, and 10 years was available for 75, 59, 50, and 15 patients, respectively. The complete occlusion rates at 1, 3, 5, and 10 years were 94.7%, 96.6%, 96.0%, and 100%, respectively. The retreatment rates at 1, 3, 5, and 10 years were 8.0%, 6.8%, 8.0%, and 6.7%, respectively. CONCLUSIONS: The authors provide their single-institution series of IA patients treated with a PED ≥ 10 years ago, with the first report of 10-year follow-up for the available patients.

A Novel Markov Model-Based Traffic Density Estimation Technique for Intelligent Transportation System.

An intelligent transportation system (ITS) aims to improve traffic efficiency by integrating innovative sensing, control, and communications technologies. The industrial Internet of things (IIoT) and Industrial Revolution 4.0 recently merged to design the industrial Internet of things-intelligent transportation system (IIoT-ITS). IIoT sensing technologies play a significant role in acquiring raw data. The application continuously performs the complex task of managing traffic flows effectively based on several parameters, including the number of vehicles in the system, their location, and time. Traffic density estimation (TDE) is another important derived parameter desirable to keep track of the dynamic state of traffic volume. The expanding number of vehicles based on wireless connectivity provides new potential to predict traffic density more accurately and in real time as previously used methodologies. We explore the topic of assessing traffic density by using only a few simple metrics, such as the number of surrounding vehicles and disseminating beacons to roadside units and vice versa. This research paper investigates TDE techniques and presents a novel Markov model-based TDE technique for ITS. Finally, an OMNET++-based approach with an implementation of a significant modification of a traffic model combined with mathematical modeling of the Markov model is presented. It is intended for the study of real-world traffic traces, the identification of model parameters, and the development of simulated traffic.

The association between hemodynamics and wall characteristics in human intracranial aneurysms: a review.

Hemodynamics plays a key role in the natural history of intracranial aneurysms (IAs). However, studies exploring the association between aneurysmal hemodynamics and the biological and mechanical characteristics of the IA wall in humans are sparse. In this review, we survey the current body of literature, summarize the studies' methodologies and findings, and assess the degree of consensus among them. We used PubMed to perform a systematic review of studies that explored the association between hemodynamics and human IA wall features using different sources. We identified 28 publications characterizing aneurysmal flow and the IA wall: 4 using resected tissues, 17 using intraoperative images, and 7 using vessel wall magnetic resonance imaging (MRI). Based on correlation to IA tissue, higher flow conditions, such as high wall shear stress (WSS) with complex pattern and elevated pressure, were associated with degenerated walls and collagens with unphysiological orientation and faster synthesis. MRI studies strongly supported that low flow, characterized by low WSS and high blood residence time, was associated with thicker walls and post-contrast enhancement. While significant discrepancies were found among those utilized intraoperative images, they generally supported that thicker walls coexist at regions with prolonged residence time and that thinner regions are mainly exposed to higher pressure with complex WSS patterns. The current body of literature supports a theory of two general hemodynamic-biologic mechanisms for IA development. One, where low flow conditions are associated with thickening and atherosclerotic-like remodeling, and the other where high and impinging flow conditions are related to wall degeneration, thinning, and collagen remodeling.

Meta-analysis of overall survival and postoperative neurologic deficits after resection or biopsy of butterfly glioblastoma.

Butterfly glioblastoma (bGBM) is a grade 4 glioma with a poor prognosis. Surgical treatment of these cancers has been reviewed in the literature with some recent studies supporting resection as a safe and effective treatment instead of biopsy and adjuvant therapy. This meta-analysis was designed to determine whether there are significant differences in overall survival (OS) and postoperative neurologic deficits (motor, speech, and cranial nerve) following intervention in patients who underwent tumor resection as part of their treatment, compared to patients who underwent biopsy without surgical resection. A literature search was conducted using PubMed (National Library of Medicine) and Embase (Elsevier) to identify articles from each database's earliest records to May 25, 2021, that directly compared the outcomes of biopsy and resection in bGBM patients and met predetermined inclusion criteria. A meta-analysis was conducted to compare the effects of the two management strategies on OS and postoperative neurologic deficits. Six articles met our study inclusion criteria. OS was found to be significantly longer for the resection group at 6 months (odds ratio [OR] 2.94, 95% confidence interval [CI] 1.23-7.05) and 12 months (OR 3.75, 95% CI 1.10-12.76) than for the biopsy group. No statistically significant differences were found in OS at 18 and 24 months. Resection was associated with an increased rate of postoperative neurologic deficit (OR 2.05, 95% CI 1.02-4.09). Resection offers greater OS up to 1 year postintervention than biopsy alone; however, this comes at the cost of higher rates of postoperative neurologic deficits.