Net water uptake within the ischemic penumbra predicts the presence of the midline shift in patients with acute ischemic stroke

ObjectiveThe study aimed to explore the association between midline shift (MLS) and net water uptake (NWU) within the ischemic penumbra in acute ischemic stroke patients.MethodsThis was a retrospective cohort study that examined patients with anterior circulation stroke. Net water uptake within the acute ischemic core and penumbra was calculated using data from admission multimodal CT scans. The primary outcome was severe cerebral edema measured by the presence of MLS on 24 to 48 h follow-up CT scans. The presence of a significant MLS was defined by a deviation of the septum pellucidum from the midline on follow-up CT scans of at least 3 mm or greater due to the mass effect of ischemic edema. The net water uptake was compared between patients with and without MLS, followed by logistic regression analyses and receiver operating characteristics (ROCs) to assess the predictive power of net water uptake in MLS.ResultsA total of 133 patients were analyzed: 50 patients (37.6%) with MLS and 83 patients (62.4%) without. Compared to patients without MLS, patients with MLS had higher net water uptake within the core [6.8 (3.2–10.4) vs. 4.9 (2.2–8.1), P = 0.048] and higher net water uptake within the ischemic penumbra [2.9 (1.8–4.3) vs. 0.2 (−2.5–2.7), P < 0.001]. Penumbral net water uptake had higher predictive performance than net water uptake of the core in MLS [area under the curve: 0.708 vs. 0.603, p < 0.001]. Moreover, the penumbral net water uptake predicted MLS in the multivariate regression model, adjusting for age, sex, admission National Institutes of Health Stroke Scale (NIHSS), diabetes mellitus, atrial fibrillation, ischemic core volume, and poor collateral vessel status (OR = 1.165; 95% CI = 1.002–1.356; P = 0.047). No significant prediction was found for the net water uptake of the core in the multivariate regression model.ConclusionNet water uptake measured acutely within the ischemic penumbra could predict severe cerebral edema at 24–48 h

Risk factors of hemorrhagic transformation in acute ischaemic stroke : A systematic review and meta-analysis

Background: Hemorrhagic transformation (HT) following reperfusion therapies for acute ischaemic stroke often predicts a poor prognosis. This systematic review and meta-analysis aims to identify risk factors for HT, and how these vary with hyperacute treatment [intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT)]. Methods: Electronic databases PubMed and EMBASE were used to search relevant studies. Pooled odds ratio (OR) with 95% confidence interval (CI) were estimated. Results: A total of 120 studies were included. Atrial fibrillation and NIHSS score were common predictors for any intracerebral hemorrhage (ICH) after reperfusion therapies (both IVT and EVT), while a hyperdense artery sign (OR = 2.605, 95% CI 1.212–5.599, I2 = 0.0%) and number of thrombectomy passes (OR = 1.151, 95% CI 1.041–1.272, I2 = 54.3%) were predictors of any ICH after IVT and EVT, respectively. Common predictors for symptomatic ICH (sICH) after reperfusion therapies were age and serum glucose level. Atrial fibrillation (OR = 3.867, 95% CI 1.970–7.591, I2 = 29.1%), NIHSS score (OR = 1.082, 95% CI 1.060–1.105, I2 = 54.5%) and onset-to-treatment time (OR = 1.003, 95% CI 1.001–1.005, I2 = 0.0%) were predictors of sICH after IVT. Alberta Stroke Program Early CT score (ASPECTS) (OR = 0.686, 95% CI 0.565–0.833, I2 =77.6%) and number of thrombectomy passes (OR = 1.374, 95% CI 1.012–1.866, I2 = 86.4%) were predictors of sICH after EVT. Conclusion: Several predictors of ICH were identified, which varied by treatment type. Studies based on larger and multi-center data sets should be prioritized to confirm the results. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=268927, identifier: CRD42021268927

Automatic segmentation of hemorrhagic transformation on follow-up non-contrast CT after acute ischemic stroke

BackgroundHemorrhagic transformation (HT) following reperfusion therapies is a serious complication for patients with acute ischemic stroke. Segmentation and quantification of hemorrhage provides critical insights into patients’ condition and aids in prognosis. This study aims to automatically segment hemorrhagic regions on follow-up non-contrast head CT (NCCT) for stroke patients treated with endovascular thrombectomy (EVT).MethodsPatient data were collected from 10 stroke centers across two countries. We propose a semi-automated approach with adaptive thresholding methods, eliminating the need for extensive training data and reducing computational demands. We used Dice Similarity Coefficient (DSC) and Lin’s Concordance Correlation Coefficient (Lin’s CCC) to evaluate the performance of the algorithm.ResultsA total of 51 patients were included, with 28 Type 2 hemorrhagic infarction (HI2) cases and 23 parenchymal hematoma (PH) cases. The algorithm achieved a mean DSC of 0.66 ± 0.17. Notably, performance was superior for PH cases (mean DSC of 0.73 ± 0.14) compared to HI2 cases (mean DSC of 0.61 ± 0.18). Lin’s CCC was 0.88 (95% CI 0.79–0.93), indicating a strong agreement between the algorithm’s results and the ground truth. In addition, the algorithm demonstrated excellent processing time, with an average of 2.7 s for each patient case.ConclusionTo our knowledge, this is the first study to perform automated segmentation of post-treatment hemorrhage for acute stroke patients and evaluate the performance based on the radiological severity of HT. This rapid and effective tool has the potential to assist with predicting prognosis in stroke patients with HT after EVT

Quantitative assessment of collateral time on perfusion computed tomography in acute ischemic stroke patients

Background and aimGood collateral circulation is recognized to maintain perfusion and contribute to favorable clinical outcomes in acute ischemic stroke. This study aimed to derive and validate an optimal collateral time measurement on perfusion computed tomography imaging for patients with acute ischemic stroke.MethodsThis study included 106 acute ischemic stroke patients with complete large vessel occlusions. In deriving cohort of 23 patients, the parasagittal region of the ischemic hemisphere was divided into six pial arterial zones according to pial branches of the middle cerebral artery. Within the 85 arterial zones with collateral vessels, the receiver operating characteristic analysis was performed to derive the optimal collateral time threshold for fast collateral flow on perfusion computed tomography. The reference for fast collateral flow was the peak contrast delay on the collateral vessels within each ischemic arterial zone compared to its contralateral normal arterial zone on dynamic computed tomography angiography. The optimal perfusion collateral time threshold was then tested in predicting poor clinical outcomes (modified Rankin score of 5–6) and final infarct volume in the validation cohort of 83 patients.ResultsFor the derivation cohort of 85 arterial zones, the optimal collateral time threshold for fast collateral flow on perfusion computed tomography was a delay time of 4.04 s [area under the curve = 0.78 (0.67, 0.89), sensitivity = 73%, and specificity = 77%]. Therefore, the delay time of 4 s was used to define the perfusion collateral time. In the validation cohort, the perfusion collateral time showed a slightly higher predicting power than dynamic computed tomography angiography collateral time in poor clinical outcomes (area under the curve = 0.72 vs. 0.67; P < 0.001). Compared to dynamic computed tomography angiography collateral time, the perfusion collateral time also had better performance in predicting final infarct volume (R-squared values = 0.55 vs. 0.23; P < 0.001).ConclusionOur results indicate that perfusion computed tomography can accurately quantify the collateral time after acute ischemic stroke

Optimal Delay Time of CT Perfusion for Predicting Cerebral Parenchymal Hematoma After Intra-Arterial tPA Treatment

Background and Purpose: Cerebral hemorrhage is a serious potential complication of stroke revascularization, especially in patients receiving intra-arterial tissue-type plasminogen activator (tPA) therapy. We investigated the optimal pre-intervention delay time (DT) of computed tomography perfusion (CTP) measurement to predict cerebral parenchymal hematoma (PH) in acute ischemic stroke (AIS) patients after intra-arterial tissue plasminogen activator (tPA) treatment.Methods: The study population consisted of a series of patients with AIS who received intra-arterial tPA treatment and had CTP and follow-up computed tomography/magnetic resonance imaging (CT/MRI) to identify hemorrhagic transformation. The association of increasing DT thresholds (>2, >4, >6, >8, and >10 s) with PH was examined using receiver operating characteristic (ROC) analysis and logistic regression.Results: Of 94 patients, 23 developed PH on follow-up imaging. Receiver operating characteristic analysis revealed that the greatest area under the curve for predicting PH occurred at DT > 4 s (area under the curve, 0.66). At this threshold of > 4 s, DT lesion volume ≥ 30.85 mL optimally predicted PH with 70% sensitivity and 59% specificity. DT > 4 s volume was independently predictive of PH in a multivariate logistic regression model (P < 0.05).Conclusions: DT > 4 s was the parameter most strongly associated with PH. The volume of moderate, not severe, hypo-perfusion on DT is more strongly associated and may allow better prediction of PH after intra-arterial tPA thrombolysis

Whole-brain CTP in acute ischemic stroke

Research Doctorate - Doctor of Philosophy (PhD)Perfusion imaging technology not only enables stroke diagnosis by identifying the ischemic lesion earlier, but also helps the clinician to make treatment decisions by further classifying the ischemic lesion into salvageable tissue and non-salvageable tissue. The imaging of salvageable tissue, penumbra, provides a direct target for reperfusion treatment. However, the accuracy of penumbra measurement with perfusion imaging has been questioned, especially with CT perfusion (CTP). Perfusion images, acquired on earlier generation instruments such as the16 or 64-detector scanners, have limited coverage of potentially ischemic brain, a factor recognised to reduce the accuracy of penumbra measurement. This limitation can be overcome by the advance in technology. The new generation “mega-detector” scanners, such as 320-detector Toshiba Aquilion One, provide whole brain coverage of 160mm from skull base to vertex. In this thesis, I presented a series of studies aiming to evaluate the utility of whole-brain CTP in acute ischemic stroke. The first study was to derive the optimal penumbra measurement on whole-brain CTP with the reference of ischemic tissue outcome, and the second study was to test the penumbra measurement of whole-brain CTP in predicting clinical patient outcome. The two studies found that only with the threshold setting at Tmax>6s or DT>3s, did the whole-brain CTP achieve high accuracy (>99%) in delineating acute ischemic penumbra and good sensitivity (>80%) in predicting favourable clinical outcome. It was also confirmed that the accuracy of penumbra measurement was comprised when the brain coverage of CTP decreased from 160mm to 20mm. Following two studies examined the utility of whole-brain CTP in the clinical setting. Firstly, CTP was compared to MRP, the perfusion modality that has already been well used in clinic. This work demonstrated that with whole brain coverage, CTP was as effective as MPR in measuring the acute penumbra and in selecting patients for reperfusion treatment. Secondly, a case by case review was carried out to assist clinicians in the interpretation CTP output. In conclusion, findings of this thesis support the usage of whole-brain CTP in acute ischemic stroke. Noticeably, the conclusion only applies to patients with anterior circulation stroke. Whole-brain CTP might also have advantage in detecting ischemic lesions in posterior circulation territory, which require studies to prove it in the future

Comparison of computed tomographic and magnetic resonance perfusion measurements in acute ischemic stroke: back-to-back quantitative analysis

Background and Purpose: Magnetic resonance perfusion (MRP) and computed tomographic perfusion (CTP) are being increasingly applied in acute stroke trials and clinical practice, yet the comparability of their perfusion values is not well validated. The aim of this study was to validate the comparability of CTP and MRP measures. Methods: A 3-step approach was used. Step 1 was a derivation step, where we analyzed 45 patients with acute ischemic stroke who had both CTP and MRP performed within 2 hours of each other and within 9 hours of stroke onset. In this step, we derived the optimal perfusion map with the least difference between MRP and CTP. In step 2, the optimal map was validated on whole-brain perfusion data of 15 patients. Step 3 was to apply the optimal perfusion map to define cross-modality reperfusion from acute CTP to 24-hour MRP in 45 patients and, in turn, to assess how accurately this predicted 3-month clinical outcome. Results: Among 8 different perfusion maps included in this study, time to peak of the residual function (T_max) was the only one with a nonsignificant difference between CTP and MRP in delineating perfusion defects. This was validated on whole-brain perfusion data, showing high concordance of T_max between the 2 modalities (concordance correlation coefficient of Lin, >0.91); the best concordance was at 6 s. At T max>6 s threshold, MRP and CTP reached substantial agreement in mismatch classification (κ >0.61). Cross-modality reperfusion calculated by T_max>6 s strongly predicted good functional outcome at 3 months (area under the curve, 0.979; P<0.05). Conclusions: MRP and CTP can be used interchangeably if one uses T_max measurement

Whole-brain CT perfusion to quantify acute ischemic penumbra and core

Purpose: To validate the use of perfusion computed tomography (CT) with whole-brain coverage to measure the ischemic penumbra and core and to compare its performance to that of limited-coverage perfusion CT. Materials and Methods: Institutional ethics committee approval and informed consent were obtained. Patients (n = 296) who underwent 320-detector CT perfusion within 6 hours of the onset of ischemic stroke were studied. First, the ischemic volume at CT perfusion was compared with the penumbra and core reference values at magnetic resonance (MR) imaging to derive CT perfusion penumbra and core thresholds. Second, the thresholds were tested in a different group of patients to predict the final infarction at diffusion-weighted imaging 24 hours after CT perfusion. Third, the change in ischemic volume delineated by the optimal penumbra and core threshold was determined as the brain coverage was gradually reduced from 160 mm to 20 mm. The Wilcoxon signed-rank test, concordance correlation coefficient (CCC), and analysis of variance were used for the first, second, and third steps, respectively. Results: CT perfusion at penumbra and core thresholds resulted in the least volumetric difference from MR imaging reference values with delay times greater than 3 seconds and delay-corrected cerebral blood flow of less than 30% (P = .34 and .33, respectively). When the thresholds were applied to the new group of patients, prediction of the final infarction was allowed with delay times greater than 3 seconds in patients with no recanalization of the occluded artery (CCC, 0.96 [95% confidence interval: 0.92, 0.98]) and with delay-corrected cerebral blood flow less than 30% in patients with complete recanalization (CCC, 0.91 [95% confidence interval: 0.83, 0.95]). However, the ischemic volume with a delay time greater than 3 seconds was underestimated when the brain coverage was reduced to 80 mm (P = .04) and the core volume measured as cerebral blood flow less than 30% was underestimated when brain coverage was 40 mm or less (P < .0001). Conclusion: Correct threshold setting and whole-brain coverage CT perfusion allowed differentiation of the penumbra from the ischemic core in patients with acute ischemic stroke

Abstract WP91: Cerebral Small Vessel Disease Burden Predicts Poor Collateral Flow in Acute Ischemic Stroke Patients With Large Artery Atherosclerosis

Aim: We sought to determine whether the extent of chronic white matter hyper-intensities (WMH) and white matter hypo-perfusion (WMHP), as markers of cerebral small vessel disease (CSVD), were associated with poor collateral flow in acute ischemic stroke as a potential cause of unfavorable functional outcome. Methods: Acute ischemic stroke patients within 12 hours of symptom onset with complete baseline and follow-up clinical data, who: (1) had large vessel occlusion in anterior circulation, (2) underwent baseline perfusion CT (CTP), (3) had 24-hour MRI were prospectively recruited. The volume of WMH was measured in the unaffected hemisphere on MRI semi-automatically. WMHP was measured as Delay Time (DT)&gt;2s in white matter of unaffected hemisphere on CTP. Quality of Collateral flow was defined by the volume ratio of DT&gt;3s/DT&gt;6s on CTP. Unfavorable functional outcome was 90-day modified Rankin Scale (mRS)&gt;2. The association between volumes of WMH, WMHP, and collateral flow were evaluated using univariate and multivariate generalized linear models. We also assessed the relationship between WMH, WHMP, and functional outcome with logistic regression. Results: There were 96 (66.6±12.81 years old, 35 female) ischemic stroke patients, and 51 were due to large artery atherosclerosis (LAA). In all patients, after multivariate adjustment, WMH volume (5.6±7.11ml) did not correlate with collateral flow (coefficient -0.01, 95% CI -0.03 to 0, P=0.09), although it was marginally associated with unfavorable outcome (Odds Ratio: 1.08, p=0.06, 95% CI 1 to 1.17). In all patients, WMHP volume (8.6±8.54ml) did not correlate with collateral flow (coefficient -0.01, 95% CI -0.01 to 0, P=0.29). However, in the LAA subgroup, WMH volume was strongly related to poorer collateral flow, i.e. lower DT&gt;3s/DT&gt;6s ratio(coefficient -0.03, 95% CI -0.04 to -0.01, P=0.01). WMHP volume was also correlated with poor collateral flow (coefficient -0.01, 95% CI -0.02 to 0, P=0.02). Conclusion: CSVD may contribute to poor collateral flow in acute stroke, especially in patients with LAA. This potentially explains the association between CSVD and poor acute stroke outcomes. </jats:p

Thresholds for infarction vary between gray matter and white matter in acute ischemic stroke: A CT perfusion study

We aimed to investigate optimal perfusion thresholds defining ischemic core and penumbra for hemispheric-cortical gray matter (GM) and subcortical white matter (WM). A total of 65 sub-6 h ischemic stroke patients were assessed, who underwent acute computed tomography perfusion (CTP) and acute magnetic resonance imaging. CTP maps were generated by both standard singular value deconvolution (sSVD) and SVD with delay and dispersion correction (ddSVD). Analyses were undertaken to calculate sensitivity, specificity, and area under the curve (AUC) for each CTP threshold for core and penumbra in GM and WM. With sSVD, the core was best defined in GM by cerebral blood flow (CBF) &lt; 30% (AUC: 0.73) and in WM by CBF &lt; 20% (AUC: 0.67). With ddSVD, GM core was best defined by CBF &lt; 35% (AUC: 0.75) and in WM by CBF &lt; 25% (AUC: 0.68). A combined GM/WM threshold overestimated core compared to diffusion-weighted imaging, CBF &lt; 25% from sSVD (1.88 ml, P = 0.007) and CBF &lt; 30% from ddSVD (1.27 ml, P = 0.011). The perfusion lesion was best defined by Tmax &gt; 5 s (AUC: 0.80) in GM and Tmax &gt; 7 s (AUC: 0.75) in WM. With sSVD, a delay time (DT) &gt; 3 s from ddSVD was the optimal for both GM (AUC: 0.78) and WM (AUC: 0.75). Using tissue-specific thresholds for GM/WM provides more accurate estimation of acute ischemic core. </jats:p