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Radiological examination of the brain is a critical determinant of stroke care pathways. Accessible neuroimaging is essential to detect the presence of intracerebral hemorrhage (ICH). Conventional magnetic resonance imaging (MRI) operates at high magnetic field strength (1.5–3 T), which requires an access-controlled environment, rendering MRI often inaccessible. We demonstrate the use of a low-field MRI (0.064 T) for ICH evaluation. Patients were imaged using conventional neuroimaging (non-contrast computerized tomography (CT) or 1.5/3 T MRI) and portable MRI (pMRI) at Yale New Haven Hospital from July 2018 to November 2020. Two board-certified neuroradiologists evaluated a total of 144 pMRI examinations (56 ICH, 48 acute ischemic stroke, 40 healthy controls) and one ICH imaging core lab researcher reviewed the cases of disagreement. Raters correctly detected ICH in 45 of 56 cases (80.4% sensitivity, 95%CI: [0.68–0.90]). Blood-negative cases were correctly identified in 85 of 88 cases (96.6% specificity, 95%CI: [0.90–0.99]). Manually segmented hematoma volumes and ABC/2 estimated volumes on pMRI correlate with conventional imaging volumes (ICC = 0.955, p  = 1.69e-30 and ICC = 0.875, p  = 1.66e-8, respectively). Hematoma volumes measured on pMRI correlate with NIH stroke scale (NIHSS) and clinical outcome (mRS) at discharge for manual and ABC/2 volumes. Low-field pMRI may be useful in bringing advanced MRI technology to resource-limited settings. Conventional magnetic resonance imaging (MRI) operates at a high magnetic field strength and requires a strict access-controlled environment, making MRI often inaccessible. Here, the authors present a portable low-field MRI device that detects intracerebral hemorrhage with high accuracy.

Abstract BACKGROUND Flow diversion for basilar apex aneurysms has rarely been reported. OBJECTIVE To assess flow diversion for basilar apex aneurysms in a multicenter cohort. METHODS Retrospective review of prospectively maintained databases at 8 academic institutions was performed from 2009 to 2016 to identify patients with basilar apex aneurysms treated with flow diversion. Clinical and radiographic data were analyzed. RESULTS Sixteen consecutive patients (median age 54.5 yr) underwent 18 procedures to treat 16 basilar apex aneurysms with either the Pipeline Embolization Device (Medtronic Inc, Dublin, Ireland) or Flow Redirection Endoluminal Device (Microvention, Tustin, California). Five aneurysms (31.3%) were treated in the setting of subarachnoid hemorrhage. Seven aneurysms (43.8%) were treated with flow diversion alone, while 9 (56.2%) underwent flow diversion and adjunctive coiling. At a median follow-up of 6 mo, complete (100%) and near-complete (90%-99%) occlusion was noted in 11 (68.8%) aneurysms. Incomplete occlusion occurred more commonly in patients treated with flow diversion alone compared to those with adjunctive coiling. Patients with partial occlusion were significantly younger. Retreatment with an additional flow diverter and adjunctive coiling occurred in 2 aneurysms with wide necks. There was 1 mortality in a patient (6.3%) who experienced posterior cerebral artery and cerebellar strokes as well as subarachnoid hemorrhage after the placement of a flow diverter. Minor complications occurred in 2 patients (12.5%). CONCLUSION Flow diversion for the treatment of basilar apex aneurysms results in acceptable occlusion rates in highly selected cases. Both primary flow diversion and rescue after failed clipping or coiling resulted in a modified Rankin Scale score that was either equal or better than at presentation and the technology represents a viable alternative or adjunctive option.

Background and Purpose Intracerebral hemorrhage (ICH) has the highest mortality rate among all strokes. While ICH location, lobar versus non-lobar, has been established as a predictor of mortality, less is known regarding the relationship between more specific ICH locations and functional outcome. This review summarizes current work studying how ICH location affects outcome, with an emphasis on how studies designate regions of interest. Methods A systematic search of the OVID database for relevant studies was conducted during August 2015. Studies containing an analysis of functional outcome by ICH location or laterality were included. As permitted, the effect size of individual studies was standardized within a meta-analysis. Results Thirty-seven studies met the inclusion criteria, the majority of which followed outcome at 3 months. Most studies found better outcomes on the Modified Rankin Scale (mRS) or Glasgow Outcome Score (GOS) with lobar compared to deep ICHs. While most aggregated deep structures for analysis, some studies found poorer outcomes for thalamic ICH in particular. Over half of the studies did not have specific methodological considerations for location designations, including blinding or validation. Conclusions Multiple studies have examined motor-centric outcomes, with few studies examining quality of life (QoL) or cognition. Better functional outcomes have been suggested for lobar versus non-lobar ICH; few studies attempted finer topographic comparisons. This study highlights the need for improved reporting in ICH outcomes research, including a detailed description of hemorrhage location, reporting of the full range of functional outcome scales, and inclusion of cognitive and QoL outcomes.

Hemolytic uremic syndrome (HUS) is a potentially life-threatening condition. It often occurs after gastrointestinal infection with E. coli O157:H7, which produces Shiga toxins (Stx) that cause hemolytic anemia, thrombocytopenia, and renal injury. Stx-mediated changes in endothelial phenotype have been linked to the pathogenesis of HUS. Here we report our studies investigating Stx-induced changes in gene expression and their contribution to the pathogenesis of HUS. Stx function by inactivating host ribosomes but can also alter gene expression at concentrations that minimally affect global protein synthesis. Gene expression profiling of human microvascular endothelium treated with Stx implicated a role for activation of CXCR4 and CXCR7 by their shared cognate chemokine ligand (stromal cell-derived factor-1 [SDF-1]) in Stx-mediated pathophysiology. The changes in gene expression required a catalytically active Stx A subunit and were mediated by enhanced transcription and mRNA stability. Stx also enhanced the association of CXCR4, CXCR7, and SDF1 mRNAs with ribosomes. In a mouse model of Stx-mediated pathology, we noted changes in plasma and tissue content of CXCR4, CXCR7, and SDF-1 after Stx exposure. Furthermore, inhibition of the CXCR4/SDF-1 interaction decreased endothelial activation and organ injury and improved animal survival. Finally, in children infected with E. coli O157:H7, plasma SDF-1 levels were elevated in individuals who progressed to HUS. Collectively, these data implicate the CXCR4/CXCR7/SDF-1 pathway in Stx-mediated pathogenesis and suggest novel therapeutic strategies for prevention and/or treatment of complications associated with E. coli O157:H7 infection.

Background: A major driver of individual variation in long-term outcomes following a large vessel occlusion (LVO) stroke is the degree of collateral arterial circulation. We aimed to develop and evaluate machine-learning models that quantify LVO collateral status using admission computed tomography angiography (CTA) radiomics. Methods: We extracted 1116 radiomic features from the anterior circulation territories from admission CTAs of 600 patients experiencing an acute LVO stroke. We trained and validated multiple machine-learning models for the prediction of collateral status based on consensus from two neuroradiologists as ground truth. Models were first trained to predict (1) good vs. intermediate or poor, or (2) good vs. intermediate or poor collateral status. Then, model predictions were combined to determine a three-tier collateral score (good, intermediate, or poor). We used the receiver operating characteristics area under the curve (AUC) to evaluate prediction accuracy. Results: We included 499 patients in training and 101 in an independent test cohort. The best-performing models achieved an averaged cross-validation AUC of 0.80 ± 0.05 for poor vs. intermediate/good collateral and 0.69 ± 0.05 for good vs. intermediate/poor, and AUC = 0.77 (0.67–0.87) and AUC = 0.78 (0.70–0.90) in the independent test cohort, respectively. The collateral scores predicted by the radiomics model were correlated with (rho = 0.45, p = 0.002) and were independent predictors of 3-month clinical outcome (p = 0.018) in the independent test cohort. Conclusions: Automated tools for the assessment of collateral status from admission CTA—such as the radiomics models described here—can generate clinically relevant and reproducible collateral scores to facilitate a timely treatment triage in patients experiencing an acute LVO stroke.

BACKGROUND:Small, blister-like aneurysms (BLAs), by virtue of their unique morphology, are difficult to treat with conventional modalities. The use of oversized self-expanding stents as monotherapy for BLAs is a relatively new and promising concept that warrants further investigation. OBJECTIVE:To clarify the role of oversized self-expanding stents as monotherapy for BLAs. METHODS:Five consecutive patients were treated for BLAs with oversized self-expanding stents alone by the senior author (K.R.B.). We report on their clinical and radiographic outcomes. RESULTS:All 5 patients in our series were discharged in good clinical condition. Complete aneurysm occlusion was observed in all patients at the time of most recent radiographic follow-up. Mean follow-up time was 13.6 months (range, 1 month to 4.5 years). CONCLUSION:The use of oversized self-expanding stents to redirect flow away from aneurysms is an effective option for patients with BLAs. This approach represents an alternative to the use of flow diverters. ABBREVIATIONS:BLA, blister-like aneurysmCTA, computed tomography angiogramICA, internal carotid arterySAH, subarachnoid hemorrhage

Intracerebral hemorrhage (ICH) is a devastating form of stroke with a high mortality rate and few treatment options. Discovery of therapeutic interventions has been slow given the challenges associated with studying acute injury in the human brain. Inflammation induced by exposure of brain tissue to blood appears to be a major part of brain tissue injury. Here, we longitudinally profiled blood and cerebral hematoma effluent from a patient enrolled in the Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation trial, offering a rare window into the local and systemic immune responses to acute brain injury. Using single-cell RNA-Seq (scRNA-Seq), this is the first report to our knowledge that characterized the local cellular response during ICH in the brain of a living patient at single-cell resolution. Our analysis revealed shifts in the activation states of myeloid and T cells in the brain over time, suggesting that leukocyte responses are dynamically reshaped by the hematoma microenvironment. Interestingly, the patient had an asymptomatic rebleed that our transcriptional data indicated occurred prior to detection by CT scan. This case highlights the rapid immune dynamics in the brain after ICH and suggests that sensitive methods such as scRNA-Seq would enable greater understanding of complex intracerebral events.

Abstract BACKGROUND Both stent-assisted coiling (SAC) and flow diversion with the Pipeline Embolization device (PED; Medtronic Inc) have been shown to be safe and clinically effective for treatment of small (<10 mm) unruptured aneurysms. However, the economic impact of these different techniques has not been established. OBJECTIVE To analyze the cost-effectiveness between stent-assisted coiling and flow diversion using PED, including procedural costs, long-term outcomes, and aneurysm recurrence. METHODS A decision-analytical study was performed with Markov modeling methods to simulate patients undergoing SAC or PED for treatment for unruptured aneurysms of sizes 5 and 7 mm. Input probabilities were derived from prior literature, and 1-way, 2-way, and probabilistic sensitivity analyses (PSA) were performed. RESULTS In base case calculation and PSA, PED was the dominant strategy for both the size groups, with and without consideration of indirect costs. One-way sensitivity analyses show that the conclusion remained robust when varying the retreatment rate of SAC from 0% to 50%, and only changes when the retreatment rate of PED > 49%. PED remained the more cost-effective strategy when the morbidity and mortality of PED increased by <55% and when those of SAC decreased by <37%. SAC only became cost-effective when the total cost of PED is >$73000 more expensive than the total cost of SAC. CONCLUSION With increasing use of PED for treatment of small unruptured anterior circulation aneurysms, our study indicates that PED is cost-effective relative to stent coiling irrespective of aneurysm size. This is due to lower aneurysm recurrence rate, as well as better health outcomes.

High-resolution magnetic resonance vessel wall imaging (MR-VWI) is increasingly used to study steno-occlusive cerebrovascular disease, but has not yet been applied to patients with aneurysmal subarachnoid hemorrhage (SAH). To study the ability of high-resolution MR-VWI to determine the site of rupture in patients with aneurysmal SAH. Medical records of patients admitted with aneurysmal SAH between December 2011 and May 2012 were reviewed. MR-VWI was routinely performed for patients treated in the IMRIS Neurovascular Suite immediately before definitive treatment of the ruptured aneurysm. We report for the first time high-resolution MR-VWI in 5 patients with aneurysmal SAH. Three patients harbored multiple intracranial aneurysms. The ruptured aneurysms demonstrated thick vessel wall enhancement in all cases. None of the associated unruptured aneurysms demonstrated this MR imaging finding. High-resolution MR-VWI identified the site of rupture in patients with aneurysmal SAH, including those patients harboring multiple intracranial aneurysms. It may represent a useful tool in the investigation of aneurysmal SAH.

To create and validate an automated pipeline for detection of early signs of irreversible ischemic change from admission CTA in patients with large vessel occlusion (LVO) stroke. We retrospectively included 368 patients for training and 143 for external validation. All patients had anterior circulation LVO stroke, endovascular therapy with successful reperfusion, and follow-up diffusion-weighted imaging (DWI). We devised a pipeline to automatically segment Alberta Stroke Program Early CT Score (ASPECTS) regions and extracted their relative Hounsfield unit (rHU) values. We determined the optimal rHU cut points for prediction of final infarction in each ASPECT region, performed 10-fold cross-validation in the training set, and measured the performance via external validation in patients from another institute. We compared the model with an expert neuroradiologist for prediction of final infarct volume and poor functional outcome. We achieved a mean area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity of 0.69±0.13, 0.69±0.09, 0.61±0.23, and 0.72±0.11 across all regions and folds in cross-validation. In the external validation cohort, we achieved a median [interquartile] AUC, accuracy, sensitivity, and specificity of 0.71 [0.68-0.72], 0.70 [0.68-0.73], 0.55 [0.50-0.63], and 0.74 [0.73-0.77], respectively. The rHU-based ASPECTS showed significant correlation with DWI-based ASPECTS (rS = 0.39, p<0.001) and final infarct volume (rS = -0.36, p<0.001). The AUC for predicting poor functional outcome was 0.66 (95%CI: 0.57-0.75). The predictive capabilities of rHU-based ASPECTS were not significantly different from the neuroradiologist's visual ASPECTS for either final infarct volume or functional outcome. Our study demonstrates the feasibility of an automated pipeline and predictive model based on relative HU attenuation of ASPECTS regions on baseline CTA and its non-inferior performance in predicting final infarction on post-stroke DWI compared to an expert human reader.