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Background For patients with large vessel occlusion (LVO) stroke, time to treatment with endovascular thrombectomy is crucial to prevent infarction and improve outcomes. We sought to evaluate the hub arrival‐to‐puncture times and outcomes for transferred patients accepted directly to the angio‐suite (LVO to operating room, LVO2OR) versus those accepted through the emergency department in a hub‐and‐spoke telestroke network. Methods Consecutive patients transferred for endovascular thrombectomy with spoke computed tomography angiography–confirmed LVO, spoke Alberta Stroke Program Early Computed Tomography score >6, and last known well–to–hub arrival

BackgroundPeak width of skeletonized mean diffusivity (PSMD) is a promising diffusion tensor imaging (DTI) marker that shows consistent and strong cognitive associations in the context of different cerebral small vessel diseases (cSVD).PurposeInvestigate whether PSMD (1) is higher in patients with Cerebral Amyloid Angiopathy (CAA) than those with arteriolosclerosis; (2) can capture the anteroposterior distribution of CAA-related abnormalities; (3) shows similar neuroimaging and cognitive associations in comparison to other classical DTI markers, such as average mean diffusivity (MD) and fractional anisotropy (FA).Materials and methodsWe analyzed cross-sectional neuroimaging and neuropsychological data from 90 non-demented memory-clinic subjects from a single center. Based on MRI findings, we classified them into probable-CAA (those that fulfilled the modified Boston criteria), subjects with MRI markers of cSVD not attributable to CAA (presumed arteriolosclerosis; cSVD), and subjects without evidence of cSVD on MRI (non-cSVD). We compared total and lobe-specific (frontal and occipital) DTI metrics values across the groups. We used linear regression models to investigate how PSMD, MD, and FA correlate with conventional neuroimaging markers of cSVD and cognitive scores in CAA.ResultsPSMD was comparable in probable-CAA (median 4.06 × 10–4 mm2/s) and cSVD (4.07 × 10–4 mm2/s) patients, but higher than in non-cSVD (3.30 × 10–4 mm2/s; p < 0.001) subjects. Occipital-frontal PSMD gradients were higher in probable-CAA patients, and we observed a significant interaction between diagnosis and region on PSMD values [F(2, 87) = 3.887, p = 0.024]. PSMD was mainly associated with white matter hyperintensity volume, whereas MD and FA were also associated with other markers, especially with the burden of perivascular spaces. PSMD correlated with worse executive function (β = −0.581, p < 0.001) and processing speed (β = −0.463, p = 0.003), explaining more variance than other MRI markers. MD and FA were not associated with performance in any cognitive domain.ConclusionPSMD is a promising biomarker of cognitive impairment in CAA that outperforms other conventional and DTI-based neuroimaging markers. Although global PSMD is similarly increased in different forms of cSVD, PSMD’s spatial variations could potentially provide insights into the predominant type of underlying microvascular pathology.

Background Access to endovascular thrombectomy (EVT) is relatively limited. Hub‐and‐spoke networks seek to transfer appropriate large‐vessel occlusion stroke candidates to EVT‐capable hubs. However, some patients are ineligible upon hub arrival, and factors that drive transfer inefficiencies are not well described. We sought to quantify EVT transfer efficiency and identify reasons for EVT ineligibility. Methods Consecutive EVT candidates presenting to 25 spokes from 2018 to 2020 with pretransfer computed tomography angiography‐defined large‐vessel occlusion and Alberta Stroke Program Early Computed Tomography Score of ≥6 were identified from a prospectively maintained database. Outcomes of interest included hub EVT, reasons for EVT ineligibility, and 90‐day modified Rankin scale score of ≤2. Results Among 258 patients, the median age was 70 years (interquartile range, 60–81 years); 50% were women. A total of 56% were ineligible for EVT after hub arrival. Cited reasons were large established infarct (49%), mild symptoms (33%), recanalization (6%), distal occlusion (5%), subocclusive lesion (3%), and goals of care (3%). Late window patients (last known well >6 hours) were more likely to be ineligible (67% versus 43%; P

Acute ischemic stroke impacts men and women differently. Here, the authors show how different lesion patterns in men and women are linked to the extent of stroke severity.

Background purposeA substantial number of patients with acute ischemic stroke (AIS) experience multiple acute lesions (MAL). We here aimed to scrutinize MAL in a large radiologically deep-phenotyped cohort.Materials and methodsAnalyses relied upon imaging and clinical data from the international MRI-GENIE study. Imaging data comprised both Fluid-attenuated inversion recovery (FLAIR) for white matter hyperintensity (WMH) burden estimation and diffusion-weighted imaging (DWI) sequences for the assessment of acute stroke lesions. The initial step featured the systematic evaluation of occurrences of MAL within one and several vascular supply territories. Associations between MAL and important imaging and clinical characteristics were subsequently determined. The interaction effect between single and multiple lesion status and lesion volume was estimated by means of Bayesian hierarchical regression modeling for both stroke severity and functional outcome.ResultsWe analyzed 2,466 patients (age = 63.4 ± 14.8, 39% women), 49.7% of which presented with a single lesion. Another 37.4% experienced MAL in a single vascular territory, while 12.9% featured lesions in multiple vascular territories. Within most territories, MAL occurred as frequently as single lesions (ratio ∼1:1). Only the brainstem region comprised fewer patients with MAL (ratio 1:4). Patients with MAL presented with a significantly higher lesion volume and acute NIHSS (7.7 vs. 1.7 ml and 4 vs. 3, pFDR < 0.001). In contrast, patients with a single lesion were characterized by a significantly higher WMH burden (6.1 vs. 5.3 ml, pFDR = 0.048). Functional outcome did not differ significantly between patients with single versus multiple lesions. Bayesian analyses suggested that the association between lesion volume and stroke severity between single and multiple lesions was the same in case of anterior circulation stroke. In case of posterior circulation stroke, lesion volume was linked to a higher NIHSS only among those with MAL.ConclusionMultiple lesions, especially those within one vascular territory, occurred more frequently than previously reported. Overall, multiple lesions were distinctly linked to a higher acute stroke severity, a higher total DWI lesion volume and a lower WMH lesion volume. In posterior circulation stroke, lesion volume was linked to a higher stroke severity in multiple lesions only.

Background Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper‐limb sensorimotor impairment. We investigated associations between non‐lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment. Methods and Results Cross‐sectional T1‐weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta‐Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA‐UE (Fugl‐Meyer Assessment of Upper Extremity). Robust mixed‐effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni‐corrected, P

Objective: To personalize the prognostication of post-stroke outcome using MRI-detected cerebrovascular pathology, we sought to investigate the association between the excessive white matter hyperintensity (WMH) burden unaccounted for by the traditional stroke risk profile of individual patients and their long-term functional outcomes after a stroke.Methods: We included 890 patients who survived after an acute ischemic stroke from the MRI-Genetics Interface Exploration (MRI-GENIE) study, for whom data on vascular risk factors (VRFs), including age, sex, atrial fibrillation, diabetes mellitus, hypertension, coronary artery disease, smoking, prior stroke history, as well as acute stroke severity, 3- to−6-month modified Rankin Scale score (mRS), WMH, and brain volumes, were available. We defined the unaccounted WMH (uWMH) burden via modeling of expected WMH burden based on the VRF profile of each individual patient. The association of uWMH and mRS score was analyzed by linear regression analysis. The odds ratios of patients who achieved full functional independence (mRS < 2) in between trichotomized uWMH burden groups were calculated by pair-wise comparisons.Results: The expected WMH volume was estimated with respect to known VRFs. The uWMH burden was associated with a long-term functional outcome (β = 0.104, p < 0.01). Excessive uWMH burden significantly reduced the odds of achieving full functional independence after a stroke compared to the low and average uWMH burden [OR = 0.4, 95% CI: (0.25, 0.63), p < 0.01 and OR = 0.61, 95% CI: (0.42, 0.87), p < 0.01, respectively].Conclusion: The excessive amount of uWMH burden unaccounted for by the traditional VRF profile was associated with worse post-stroke functional outcomes. Further studies are needed to evaluate a lifetime brain injury reflected in WMH unrelated to the VRF profile of a patient as an important factor for stroke recovery and a plausible indicator of brain health.

ObjectiveNeuroimaging measurements of brain structural integrity are thought to be surrogates for brain health, but precise assessments require dedicated advanced image acquisitions. By means of quantitatively describing conventional images, radiomic analyses hold potential for evaluating brain health. We sought to: (1) evaluate radiomics to assess brain structural integrity by predicting white matter hyperintensities burdens (WMH) and (2) uncover associations between predictive radiomic features and clinical phenotypes.MethodsWe analyzed a multi-site cohort of 4,163 acute ischemic strokes (AIS) patients with T2-FLAIR MR images with total brain and WMH segmentations. Radiomic features were extracted from normal-appearing brain tissue (brain mask–WMH mask). Radiomics-based prediction of personalized WMH burden was done using ElasticNet linear regression. We built a radiomic signature of WMH with stable selected features predictive of WMH burden and then related this signature to clinical variables using canonical correlation analysis (CCA).ResultsRadiomic features were predictive of WMH burden (R2 = 0.855 ± 0.011). Seven pairs of canonical variates (CV) significantly correlated the radiomics signature of WMH and clinical traits with respective canonical correlations of 0.81, 0.65, 0.42, 0.24, 0.20, 0.15, and 0.15 (FDR-corrected p-valuesCV1–6 < 0.001, p-valueCV7 = 0.012). The clinical CV1 was mainly influenced by age, CV2 by sex, CV3 by history of smoking and diabetes, CV4 by hypertension, CV5 by atrial fibrillation (AF) and diabetes, CV6 by coronary artery disease (CAD), and CV7 by CAD and diabetes.ConclusionRadiomics extracted from T2-FLAIR images of AIS patients capture microstructural damage of the cerebral parenchyma and correlate with clinical phenotypes, suggesting different radiographical textural abnormalities per cardiovascular risk profile. Further research could evaluate radiomics to predict the progression of WMH and for the follow-up of stroke patients’ brain health.

White matter hyperintensities of presumed vascular origin (WMH) are a prevalent form of cerebral small-vessel disease and an important risk factor for post-stroke cognitive dysfunction. Despite this prevalence, it is not well understood how WMH contributes to post-stroke cognitive dysfunction. Preliminary findings suggest that increasing WMH volume is associated with total hippocampal volume in chronic stroke patients. The hippocampus, however, is a complex structure with distinct subfields that have varying roles in the function of the hippocampal circuitry and unique anatomical projections to different brain regions. For these reasons, an investigation into the relationship between WMH and hippocampal subfield volume may further delineate how WMH predispose to post-stroke cognitive dysfunction. In a prospective study of acute ischemic stroke patients with moderate/severe WMH burden, we assessed the relationship between quantitative WMH burden and hippocampal subfield volumes. Patients underwent a 3T MRI brain within 2–5 days of stroke onset. Total WMH volume was calculated in a semi-automated manner. Mean cortical thickness and hippocampal volumes were measured in the contralesional hemisphere. Total and subfield hippocampal volumes were measured using an automated, high-resolution, ex vivo computational atlas. Linear regression analyses were performed for predictors of total and subfield hippocampal volumes. Forty patients with acute ischemic stroke and moderate/severe white matter hyperintensity burden were included in this analysis. Median WMH volume was 9.0 cm3. Adjusting for intracranial volume and stroke laterality, age (β = −3.7, P < 0.001), hypertension (β = −44.7, P = 0.04), WMH volume (β = −0.89, P = 0.049), and mean cortical thickness (β = 286.2, P = 0.006) were associated with total hippocampal volume. In multivariable analysis, age (β = −3.3, P < 0.001) and cortical thickness (β = 205.2, P = 0.028) remained independently associated with total hippocampal volume. In linear regression for predictors of hippocampal subfield volume, increasing WMH volume was associated with decreased hippocampal-amygdala transition area volume (β = −0.04, P = 0.001). These finding suggest that in ischemic stroke patients, increased WMH burden is associated with selective hippocampal subfield degeneration in the hippocampal-amygdala transition area.

Objective: To determine whether the rich-club organization, essential for information transport in the human connectome, is an important biomarker of functional outcome after acute ischemic stroke (AIS).Methods: Consecutive AIS patients (N = 344) with acute brain magnetic resonance imaging (MRI) (

Purpose: White matter hyperintensity (WMH) is a common phenotype across a variety of neurological diseases, particularly prevalent in stroke patients; however, vascular territory dependent variation in WMH burden has not yet been identified. Here, we sought to investigate the spatial specificity of WMH burden in patients with acute ischemic stroke (AIS).Materials and Methods: We created a novel age-appropriate high-resolution brain template and anatomically delineated the cerebral vascular territories. We used WMH masks derived from the clinical T2 Fluid Attenuated Inverse Recovery (FLAIR) MRI scans and spatial normalization of the template to discriminate between WMH volume within each subject's anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) territories. Linear regression modeling including age, sex, common vascular risk factors, and TOAST stroke subtypes was used to assess for spatial specificity of WMH volume (WMHv) in a cohort of 882 AIS patients.Results: Mean age of this cohort was 65.23 ± 14.79 years, 61.7% were male, 63.6% were hypertensive, 35.8% never smoked. Mean WMHv was 11.58c ± 13.49 cc. There were significant differences in territory-specific, relative to global, WMH burden. In contrast to PCA territory, age (0.018 ± 0.002, p < 0.001) and small-vessel stroke subtype (0.212 ± 0.098, p < 0.001) were associated with relative increase of WMH burden within the anterior (ACA and MCA) territories, whereas male sex (−0.275 ± 0.067, p < 0.001) was associated with a relative decrease in WMHv.Conclusions: Our data establish the spatial specificity of WMH distribution in relation to vascular territory and risk factor exposure in AIS patients and offer new insights into the underlying pathology.

Despite the proven efficacy of intravenous alteplase or endovascular thrombectomy for the treatment of patients with acute ischemic stroke, only a minority receive these treatments. This low treatment rate is due in large part to delay in hospital arrival or uncertainty as to the exact time of onset of ischemic stroke, which renders patients outside the current guideline-recommended window of eligibility for receiving these therapeutics. However, recent pivotal clinical trials of late-window thrombectomy now force us to rethink the value of a simplistic chronological formulation that “time is brain.” We must recognize a more nuanced concept that the rate of tissue death as a function of time is not invariant, that still salvageable tissue at risk of infarction may be present up to 24 h after last-known well, and that those patients may strongly benefit from reperfusion. Multiple studies have sought to address this clinical dilemma using neuroimaging methods to identify a radiographic time-stamp of stroke onset or evidence of salvageable ischemic tissue and thereby increase the number of patients eligible for reperfusion therapies. In this review, we provide a critical analysis of the current state of neuroimaging techniques to select patients with unwitnessed stroke for revascularization therapies and speculate on the future direction of this clinically relevant area of stroke research.

Introduction: The care of emergent large vessel occlusion (ELVO) stroke patients has been revolutionized by endovascular thrombectomy (EVT). Given its robust efficacy, it is crucial to optimize delivery to eligible patients. Within hub‐and‐spoke hospital system models, some patients first present to distant spoke hospitals and require transfer to hub hospitals for EVT. We sought to understand reasons EVT candidates become ineligible after transfer for treatment. Methods: Consecutive EVT candidates presenting to 25 spokes from 2018 to 2020 with pre‐transfer CTA‐defined ELVO and Alberta Stroke Program Early CT Score ≥6 were identified from a prospectively maintained database. Outcomes of interest included hub EVT, reasons for EVT ineligibility, and 90‐day functional independence (modified Rankin Scale, mRS ≤2). Results: 258 patients were identified with median age 70 years (IQR 60–81) and 50% female. 44% underwent EVT upon hub arrival, of which 87% achieved Thrombolysis in Cerebral Infarction 2b‐3 reperfusion. Compared to EVT‐eligible patients, ineligible patients were older (73 vs 68 years, p = 0.04), had lower NIH Stroke Scale (NIHSS, 10 vs 16, p