In vivo human brain extracellular fluids (ECF) of acute stroke patients were investigated to assess the changes in protein levels associated with ischemic damages. Microdialysates (MDs) from the ...infarct core (IC), the penumbra (P), and the unaffected contralateral (CT) brain regions of patients suffering an ischemic stroke (n = 6) were compared using a shotgun proteomic approach based on isobaric tagging and mass spectrometry. Quantitative analysis showed 53 proteins with increased amounts in the IC or P with respect to the CT samples. Glutathione S-transferase P (GSTP1), peroxiredoxin-1 (PRDX1), and protein S100-B (S100B) were further assessed with ELISA on the blood of unrelated control (n = 14) and stroke (n = 14) patients. Significant increases of 8- (p = 0.0002), 20- (p = 0.0001), and 11-fold (p = 0.0093) were found, respectively. This study highlights the value of ECF as an efficient source to further discover blood stroke markers.
Objective:
To determine the association between baseline ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) antigen level and 90-days clinical outcome in ...patients with acute ischemic stroke (AIS) receiving recombinant tissue plasminogen activator (rt-PA) thrombolysis.
Methods:
AIS patients receiving rt-PA thrombolytic therapy from Huashan Hospital and Fifth People's Hospital of Shanghai, China in 2014–2017 were consecutively enrolled. Blood samples for ADAMTS13 tests were drawn before intravenous rt-PA administration. The primary outcome was defined as the poor functional outcome of modified Rankin Scale (mRS) >2 at 90-days follow-up. Secondary outcome was hemorrhagic transformation after rt-PA therapy. Moreover, for AIS patients with large vessel occlusion from Huashan Hospital, the association between baseline ADAMTS13 level and cerebral collateral flow was also assessed.
Results:
A total of 163 AIS patients (median age 66.2 years, 63.8% male) were included. Baseline ADAMTS13 level was marginally decreased in patients with 90-days mRS >2 than in those with mRS ≤ 2 (mean ± SD, 1458.4 ± 323.3 vs. 1578.3 ± 395.4 ng/mL,
p
= 0.046). However, no difference of ADAMTS13 level was found after adjusting for age, history of atrial fibrillation, glycemia, baseline NIHSS score and TOAST classification (
p
= 0.43). We found no difference in ADAMTS13 level between patients with parenchymal hemorrhage after rt-PA therapy and those without (
p
= 0.44). Among 66 patients with large vessel occlusion, there was also no association between ADAMTS13 level and cerebral collateral flow in multivariable analyses.
Conclusion:
In our cohort, blood ADAMTS13 antigen level before rt-PA therapy could not be used as an independent biomarker in predicting clinical outcomes of AIS patients at 90 days.
Objective
We compared outcomes and adverse events of thrombectomy versus medical management in acute ischemic stroke (AIS) patients with baseline large infarct core.
Methods
We searched Ovid ...MEDLINE(R) ALL, Cochrane Library Clinical Controlled Trials and EMBASE from inception to January 2021 for studies comparing thrombectomy and medical management alone in AIS patients who had ASPECTS <=7 or ischemic core volume >=50 ml. Imaging modalities to valuate ASPECTS and core volume were without restriction. The functional outcome was measured by mRS (modified Rankin Scale) score 0-2 at 90 days or discharge. The safety end point included the rates of mortality and sICH (symptomatic intracranial hemorrhage) or PH2 (parenchymal hematoma type 2).
Results
Fourteen studies with a total of 2547 patients (thrombectomy n = 1197; medical care alone n = 1350) fulfilled our criteria. As for patients with low ASPECTS, pooled results indicated a higher odds of good functional outcome (OR = 3.47; 95% CI 1.99 to 6.07; P < 0.0001, I2=66%) and a lower risk of mortality (OR = 0.62; 95% CI 0.46 to 0.83; P = 0.001, I2=32%) in thrombectomy group compared with no thrombectomy group, but the risk of sICH or PH2 did not differ between two groups. As for patients with large core volume, both functional outcome and safety end point between two groups showed no statistically significant difference.
Conclusion
Thrombectomy remained safe and effective by careful selection in patients with low ASPECTS. More studies were warranted to explore contraindications for mechanical thrombectomy in AIS patients, especially in patients with large core volume.
Estimates of parameters used to select patients for endovascular thrombectomy (EVT) for acute ischemic stroke differ among software packages for automated computed tomography (CT) perfusion analysis. ...To determine impact of these differences in decision making, we analyzed intra-observer and inter-observer agreement in recommendations about whether to perform EVT based on perfusion maps from 4 packages.
Perfusion CT datasets from 63 consecutive patients with suspected acute ischemic stroke were retrospectively postprocessed with 4 packages of Minerva, RAPID, Olea, and IntelliSpace Portal (ISP). We used Pearson correlation coefficients and Bland-Altman analysis to compare volumes of infarct core, penumbra, and mismatch calculated by Minerva and RAPID. We used kappa analysis to assess agreement among decisions of 3 radiologists about whether to recommend EVT based on maps generated by 4 packages.
We found significant differences between using Minerva and RAPID to estimate penumbra (67.39±41.37mL vs. 78.35±45.38 mL, p < 0.001) and mismatch (48.41±32.03 vs. 61.27±32.73mL, p < 0.001), but not of infarct core (p = 0.230). Pearson correlation coefficients were 0.94 (95%CI:0.90-0.96) for infarct core, 0.87 (95%CI:0.79-0.91) for penumbra, and 0.72 (95%CI:0.57-0.83) for mismatch volumes (p < 0.001). Limits of agreements were (-21.22-25.02) for infarct core volumes, (-54.79-32.88) for penumbra volumes, and (-60.16-34.45) for mismatch volumes. Final agreement for EVT decision-making was substantial between Minerva vs. RAPID (k = 0.722), Minerva vs. Olea (k = 0.761), and RAPID vs. Olea (k = 0.782), but moderate for ISP vs. the other three.
Despite quantitative differences in estimates of infarct core, penumbra, and mismatch using 4 software packages, their impact on radiologists' decisions about EVT is relatively small.
Large clinical trials have helped establish the benefit of endovascular treatment (EVT) in patients with acute ischemic stroke with large vessel occlusion and small infarct core volume as determined ...by scores ≥6 on the Alberta Stroke Program Early CT Scores. Several small studies have suggested that patients with large infarct core volume (LICV) may also benefit from EVT. Currently, at least 6 randomized clinical trials are examining the benefit of extending EVT to this population of patients with acute ischemic stroke. These trials were independently conceived and have significant differences in their inclusion criteria. Understanding these inclusion criteria and other differences in trial design is pivotal for the field to interpret the upcoming results of these trials. In this review, the designs of the 6 trials are summarized and compared. Specific differences are described, including (1) the rationale for EVT treatment in patients with LICV, (2) how to define LICV and the imaging modality used to identify LICV, (3) inclusion of an Alberta Stroke Program Early CT Score 0 to 5 versus 3 to 5, (4) use of the mismatch between blood flow and the size of infarct as an inclusion criterion, and (5) inclusion of early window and/or late window patients. The potential impact of these trial results on current guidelines for acute ischemic stroke is discussed. Differences in trial design as well as inclusion and exclusion criteria may influence trial outcomes. The implications of these trial results will likely be enhanced by a pooled analysis.
IntroductionTo compare the perfusion volumes assessed by a new automated CT perfusion (CTP) software iStroke with the circular singular value decomposition software RAPID and determine its predictive ...value for functional outcome in patients with acute ischaemic stroke (AIS) who underwent endovascular treatment (EVT).MethodsData on patients with AIS were collected from four hospitals in China. All patients received CTP followed by EVT with complete recanalisation within 24 hours of symptom onset. We evaluated the agreement of CTP measures between the two softwares by Spearman’s rank correlation tests and kappa tests. Bland-Altman plots were used to evaluate the agreement of infarct core volume (ICV) on CTP and ground truth on diffusion-weighted imaging (DWI). Logistic regression models were used to test the association between ICV on these two softwares and functional outcomes.ResultsAmong 326 patients, 228 had DWI examinations and 40 of them had infarct volume >70 mL. In all patients, the infarct core and hypoperfusion volumes on iStroke had a strong correlation with those on RAPID (ρ=0.68 and 0.66, respectively). The agreement of large infarct core (volume >70 mL) was substantial (kappa=0.73, p<0.001) between these two softwares. The ICV measured by iStroke and RAPID was significantly correlated with independent functional outcome at 90 days (p=0.009 and p<0.001, respectively). In patients with DWI examinations and those with an ICV >70 mL, the ICV of iStroke and RAPID was comparable on individual agreement with ground truth.ConclusionThe automatic CTP software iStroke is a reliable tool for assessing infarct core and mismatch volumes, making it clinically useful for selecting patients with AIS for acute reperfusion therapy in the extended time window.
Purpose: To assess acute ischemic stroke (AIS) severity, infarct is segmented using computed tomography perfusion (CTP) software, such as RAPID, Sphere, and Vitrea, relying on contralateral ...hemisphere thresholds. Since this approach is potentially patient dependent, we investigated whether convolutional neural networks (CNNs) could achieve better performances without the need for contralateral hemisphere thresholds.
Approach: CTP and diffusion-weighted imaging (DWI) data were retrospectively collected for 63 AIS patients. Cerebral blood flow (CBF), cerebral blood volume (CBV), time-to-peak, mean-transit-time (MTT), and delay time maps were generated using Vitrea CTP software. U-net shaped CNNs were developed, trained, and tested for 26 different input CTP parameter combinations. Infarct labels were segmented from DWI volumes registered with CTP volumes. Infarct volumes were reconstructed from two-dimensional CTP infarct segmentations. To remove erroneous segmentations, conditional random field (CRF) postprocessing was applied and compared with prior results. Spatial and volumetric infarct agreement was assessed between DWI and CTP (CNNs and commercial software) using median infarct difference, median absolute error, dice coefficient, positive predictive value.
Results: The most accurate combination of parameters for CNN segmenting infarct using CRF postprocessing was CBF, CBV, and MTT (4.83 mL, 10.14 mL, 0.66, 0.73). Commercial software results are: RAPID = (2.25 mL, 21.48 mL, 0.63, 0.70), Sphere = (7.57 mL, 17.74 mL, 0.64, 0.70), Vitrea = (6.79 mL, 15.28 mL, 0.63, 0.72).
Conclusions: Use of CNNs with multiple input perfusion parameters has shown to be accurate in segmenting infarcts and has the ability to improve clinical workflow by eliminating the need for contralateral hemisphere comparisons.
Purpose
To investigate the rate of neurological functional independence (NFI) at 90 days in patients with large infarct core (LIC), which was evaluated by different imaging modalities before ...endovascular thrombectomy (EVT).
Methods
PubMed and EMBASE were searched for original studies on clinical functional outcomes at 90 days in LIC patients who received EVT treatment from inception to 28 September 2021. The pooled NFI rates were calculated using random effects model according to different imaging modalities and criteria.
Results
We included 34 studies enrolling 2997 LIC patients. The NFI rates were 23% (95% confidence interval, CI 15–32%) and 24% (95% CI 10–38%) when LIC was defined as core volume ≥50 ml and ≥ 70 ml separately on computed tomography perfusion, 36% (95% CI 23–48%) and 21% (95% CI 17–25%) when LIC was defined as core volume ≥ 50 ml and ≥ 70 ml separately on magnetic resonance diffusion-weighted imaging (DWI), 28% (95% CI 24–32%) and 37% (95% CI 21–53%) when LIC was defined as DWI-ASPECTS ≤ 5 and ≤ 6 separately, 23% (95% CI 19–27%) and 32% (95% CI 18–46%) when LIC was defined as NCCT-ASPECTS ≤ 5 and ≤ 6 separately.
Conclusion
Similar NFI rates could be obtained after EVT in LIC patients if proper LIC criteria were select according to the imaging modality.
Recent trials have shown promise in intra-arterial thrombectomy after the first 6-24 h of stroke onset. Quick and precise identification of the salvageable tissue is essential for successful stroke ...management. In this study, we examined the feasibility of machine learning (ML) approaches for differentiating the ischemic penumbra (IP) from the infarct core (IC) by using diffusion tensor imaging (DTI)-derived metrics.
Fourteen male rats subjected to permanent middle cerebral artery occlusion (pMCAO) were included in this study. Using a 7 T magnetic resonance imaging, DTI metrics such as fractional anisotropy, pure anisotropy, diffusion magnitude, mean diffusivity (MD), axial diffusivity, and radial diffusivity were derived. The MD and relative cerebral blood flow maps were coregistered to define the IP and IC at 0.5 h after pMCAO. A 2-level classifier was proposed based on DTI-derived metrics to classify stroke hemispheres into the IP, IC, and normal tissue (NT). The classification performance was evaluated using leave-one-out cross validation.
The IC and non-IC can be accurately segmented by the proposed 2-level classifier with an area under the receiver operating characteristic curve (AUC) between 0.99 and 1.00, and with accuracies between 96.3 and 96.7%. For the training dataset, the non-IC can be further classified into the IP and NT with an AUC between 0.96 and 0.98, and with accuracies between 95.0 and 95.9%. For the testing dataset, the classification accuracy for IC and non-IC was 96.0 ± 2.3% whereas for IP and NT, it was 80.1 ± 8.0%. Overall, we achieved the accuracy of 88.1 ± 6.7% for classifying three tissue subtypes (IP, IC, and NT) in the stroke hemisphere and the estimated lesion volumes were not significantly different from those of the ground truth (p = .56, .94, and .78, respectively).
Our method achieved comparable results to the conventional approach using perfusion-diffusion mismatch. We suggest that a single DTI sequence along with ML algorithms is capable of dichotomizing ischemic tissue into the IC and IP.
To determine whether infarct core or penumbra is the more significant predictor of outcome in acute ischemic stroke, and whether the results are affected by the statistical method used.
Clinical and ...imaging data were collected in 165 patients with acute ischemic stroke. We reviewed the noncontrast head computed tomography (CT) to determine the Alberta Score Program Early CT score and assess for hyperdense middle cerebral artery. We reviewed CT-angiogram for site of occlusion and collateral flow score. From perfusion-CT, we calculated the volumes of infarct core and ischemic penumbra. Recanalization status was assessed on early follow-up imaging. Clinical data included age, several time points, National Institutes of Health Stroke Scale at admission, treatment type, and modified Rankin score at 90 days. Two multivariate regression analyses were conducted to determine which variables predicted outcome best. In the first analysis, we did not include recanalization status among the potential predicting variables. In the second, we included recanalization status and its interaction between perfusion-CT variables.
Among the 165 study patients, 76 had a good outcome (modified Rankin score ≤2) and 89 had a poor outcome (modified Rankin score >2). In our first analysis, the most important predictors were age (P<0.001) and National Institutes of Health Stroke Scale at admission (P=0.001). The imaging variables were not important predictors of outcome (P>0.05). In the second analysis, when the recanalization status and its interaction with perfusion-CT variables were included, recanalization status and perfusion-CT penumbra volume became the significant predictors (P<0.001).
Imaging prediction of tissue fate, more specifically imaging of the ischemic penumbra, matters only if recanalization can also be predicted.
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