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Key points CTP-estimated ischemic core has moderate volumetric and spatial agreement with the infarct lesion on 24 h follow-up DWI. The studied CTP software shows similar performance to the most used CTP softwares and can be used interchangeably. Severe ischemic core overestimation by the CTP software was relatively uncommon.

Background: Computed tomography perfusion (CTP)-estimated core volume is associated with functional outcomes in acute ischemic stroke. This relationship might differ among patients, depending on brain volume. Materials and Methods: We retrospectively included patients from the MR CLEAN Registry. Cerebrospinal fluid (CSF) and intracranial volume (ICV) were automatically segmented on NCCT. We defined the proportion of the ICV and total brain volume (TBV) affected by the ischemic core as ICVcore and TBVcore. Associations between the core volume, ICVcore, TBVcore, and functional outcome are reported per interquartile range (IQR). We calculated the area under the curve (AUC) to assess diagnostic accuracy. Results: In 200 patients, the median core volume was 13 (5–41) mL. Median ICV and TBV were 1377 (1283–1456) mL and 1108 (1020–1197) mL. Median ICVcore and TBVcore were 0.9 (0.4–2.8)% and 1.7 (0.5–3.6)%. Core volume (acOR per IQR 0.48 [95%CI 0.33–0.69]), ICVcore (acOR per IQR 0.50 [95%CI 0.35–0.69]), and TBVcore (acOR per IQR 0.41 95%CI 0.33–0.67]) showed a lower likelihood of achieving improved functional outcomes after 90 days. The AUC was 0.80 for the prediction of functional independence at 90 days for the CTP-estimated core volume, the ICVcore, and the TBVcore. Conclusion: Correcting the CTP-estimated core volume for the intracranial or total brain volume did not improve the association with functional outcomes in patients who underwent EVT.

Computed tomography perfusion (CTP) is frequently used in the triage of ischemic stroke patients for endovascular thrombectomy (EVT). We aimed to quantify the volumetric and spatial agreement of the CTP ischemic core estimated with different thresholds and follow-up MRI infarct volume on diffusion-weighted imaging (DWI). Patients treated with EVT between November 2017 and September 2020 with available baseline CTP and follow-up DWI were included. Data were processed with Philips IntelliSpace Portal using four different thresholds. Follow-up infarct volume was segmented on DWI. In 55 patients, the median DWI volume was 10 mL, and median estimated CTP ischemic core volumes ranged from 10–42 mL. In patients with complete reperfusion, the intraclass correlation coefficient (ICC) showed moderate-good volumetric agreement (range 0.55–0.76). A poor agreement was found for all methods in patients with successful reperfusion (ICC range 0.36–0.45). Spatial agreement (median Dice) was low for all four methods (range 0.17–0.19). Severe core overestimation was most frequently (27%) seen in Method 3 and patients with carotid-T occlusion. Our study shows moderate–good volumetric agreement between ischemic core estimates for four different thresholds and subsequent infarct volume on DWI in EVT-treated patients with complete reperfusion. The spatial agreement was similar to other commercially available software packages.

Background: A considerable proportion of acute ischemic stroke patients treated with endovascular thrombectomy (EVT) are dead or severely disabled at 3 months despite successful reperfusion. Ischemic core imaging biomarkers may help to identify patients who are more likely to have a poor outcome after endovascular thrombectomy (EVT) despite successful reperfusion. We studied the association of CT perfusion-(CTP), CT angiography-(CTA), and non-contrast CT-(NCCT) based imaging markers with poor outcome in patients who underwent EVT in daily clinical practice.Methods: We included EVT-treated patients (July 2016–November 2017) with an anterior circulation occlusion from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry with available baseline CTP, CTA, and NCCT. We used multivariable binary and ordinal logistic regression to analyze the association of CTP ischemic core volume, CTA-Collateral Score (CTA-CS), and Alberta Stroke Program Early CT Score (ASPECTS) with poor outcome (modified Rankin Scale score (mRS) 5-6) and likelihood of having a lower score on the mRS at 90 days.Results: In 201 patients, median core volume was 13 (IQR 5-41) mL. Median ASPECTS was 9 (IQR 8-10). Most patients had grade 2 (83/201; 42%) or grade 3 (28/201; 14%) collaterals. CTP ischemic core volume was associated with poor outcome [aOR per 10 mL 1.02 (95%CI 1.01–1.04)] and lower likelihood of having a lower score on the mRS at 90 days [aOR per 10 mL 0.85 (95% CI 0.78–0.93)]. In multivariable analysis, neither CTA-CS nor ASPECTS were significantly associated with poor outcome or the likelihood of having a lower mRS.Conclusion: In our population of patients treated with EVT in daily clinical practice, CTP ischemic core volume is associated with poor outcome and lower likelihood of shift toward better outcome in contrast to either CTA-CS or ASPECTS.

Infarct volume (FIV) on follow-up diffusion-weighted imaging (FU-DWI) is only moderately associated with functional outcome in acute ischemic stroke patients. However, FU-DWI may contain other imaging biomarkers that could aid in improving outcome prediction models for acute ischemic stroke. We included FU-DWI data from the HERMES, ISLES, and MR CLEAN-NO IV databases. Lesions were segmented using a deep learning model trained on the HERMES and ISLES datasets. We assessed the performance of three classifiers in predicting functional independence for the MR CLEAN-NO IV trial cohort based on: (1) FIV alone, (2) the most important features obtained from a trained convolutional autoencoder (CAE), and (3) radiomics. Furthermore, we investigated feature importance in the radiomic-feature-based model. For outcome prediction, we included 206 patients: 144 scans were included in the training set, 21 in the validation set, and 41 in the test set. The classifiers that included the CAE and the radiomic features showed AUC values of 0.88 and 0.81, respectively, while the model based on FIV had an AUC of 0.79. This difference was not found to be statistically significant. Feature importance results showed that lesion intensity heterogeneity received more weight than lesion volume in outcome prediction. This study suggests that predictions of functional outcome should not be based on FIV alone and that FU-DWI images capture additional prognostic information.

Thrombus imaging characteristics are associated with treatment success and functional outcomes in stroke patients. However, assessing these characteristics based on manual annotations is labor intensive and subject to observer bias. Therefore, we aimed to create an automated pipeline for consistent and fast full thrombus segmentation. We used multi-center, multi-scanner datasets of anterior circulation stroke patients with baseline NCCT and CTA for training (n = 228) and testing (n = 100). We first found the occlusion location using StrokeViewer LVO and created a bounding box around it. Subsequently, we trained dual modality U-Net based convolutional neural networks (CNNs) to segment the thrombus inside this bounding box. We experimented with: (1) U-Net with two input channels for NCCT and CTA, and U-Nets with two encoders where (2) concatenate, (3) add, and (4) weighted-sum operators were used for feature fusion. Furthermore, we proposed a dynamic bounding box algorithm to adjust the bounding box. The dynamic bounding box algorithm reduces the missed cases but does not improve Dice. The two-encoder U-Net with a weighted-sum feature fusion shows the best performance (surface Dice 0.78, Dice 0.62, and 4% missed cases). Final segmentation results have high spatial accuracies and can therefore be used to determine thrombus characteristics and potentially benefit radiologists in clinical practice.

Background and Purpose: The morbidity and early mortality associated with stroke is largely attributable to cerebral edema and elevated intracranial pressure (ICP). Existing pharmacotherapies do not target the underlying pathophysiology and are often ineffective in sustainably lowering ICP, whilst decompressive craniectomy (DC) surgery is life-saving yet with surgical/peri-operative risk and increased morbidity in the elderly. Accordingly, there is an urgent need for therapies that directly target the mechanisms of edema genesis. Neurogenic inflammation, mediated by substance P (SP) binding to the tachykinin NK1 receptor (NK1-r), is associated with blood-brain barrier (BBB) disruption, cerebral edema and poor outcome post-stroke. NK1-r antagonist treatment ameliorates BBB dysfunction and cerebral edema in rodent stroke models. However, treatment has not been investigated in a large animal model, an important step toward clinical translation. Consequently, the current study compared the efficacy of NK1-r antagonist treatment to DC surgery in reducing ICP post-stroke in a clinically relevant ovine model.Methods: Anesthetized female Merino sheep (65 ± 6 kg, 18–24 months) underwent sham surgery (n = 4) or permanent middle cerebral artery occlusion (n = 22). Stroke animals were randomized into one of 5 treatments: 1×NK1 bolus (4 h), 2×NK1 bolus (4 h;9 h), 3×NK1 bolus (4 h;9 h;14 h), DC surgery (performed at 4 h) or saline vehicle. ICP, blood pressure and blood gasses were monitored for 24 h post-stroke. At 24 h post-stroke anesthetized animals underwent MRI followed by perfusion and brains removed and processed for histological assessment.Results: 2×NK1, 3×NK1 administration or DC surgery significantly (p < 0.05) reduced ICP compared to vehicle. 1×NK1 was ineffective in sustainably lowering ICP. On MRI, midline shift and cerebral edema were more marked in vehicles compared to NK1-r treatment groups.Conclusion: Two or three boluses of NK1-r antagonist treatment reduced ICP comparable to DC surgery, suggesting it may provide a novel alternative to invasive surgery for the management of elevated ICP.

Background and PurposeCerebral edema and elevated intracranial pressure (ICP) are the leading cause of death in the first week following stroke. Despite this, current treatments are limited and fail to address the underlying mechanisms of swelling, highlighting the need for targeted treatments. When screening promising novel agents, it is essential to use clinically relevant large animal models to increase the likelihood of successful clinical translation. As such, we sought to develop a survival model of transient middle cerebral artery occlusion (tMCAO) in the sheep and subsequently characterize the temporal profile of cerebral edema and elevated ICP following stroke in this novel, clinically relevant model.MethodsMerino-sheep (27M;31F) were anesthetized and subject to 2 h tMCAO with reperfusion or sham surgery. Following surgery, animals were allowed to recover and returned to their home pens. At preselected times points ranging from 1 to 7 days post-stroke, animals were re-anesthetized, ICP measured for 4 h, followed by imaging with MRI to determine cerebral edema, midline shift and infarct volume (FLAIR, T2 and DWI). Animals were subsequently euthanized and their brain removed for immunohistochemical analysis. Serum and cerebrospinal fluid samples were also collected and analyzed for substance P (SP) using ELISA.ResultsIntracranial pressure and MRI scans were normal in sham animals. Following stroke, ICP rose gradually over time and by 5 days was significantly (p < 0.0001) elevated above sham levels. Profound cerebral edema was observed as early as 2 days post-stroke and continued to evolve out to 6 days, resulting in significant midline shift which was most prominent at 5 days post-stroke (p < 0.01), in keeping with increasing ICP. Serum SP levels were significantly elevated (p < 0.01) by 7 days post-tMCAO.ConclusionWe have successfully developed a survival model of ovine tMCAO and characterized the temporal profile of ICP. Peak ICP elevation, cerebral edema and midline shift occurred at days 5–6 following stroke, accompanied by an elevation in serum SP. Our findings suggest that novel therapeutic agents screened in this model targeting cerebral edema and elevated ICP would most likely be effective when administered prior to 5 days, or as early as possible following stroke onset.

Background and objectiveComputed tomography perfusion (CTP) is widely used in the evaluation of acute ischemic stroke patients for endovascular thrombectomy (EVT). The stability of CTP core estimation is suboptimal and varies between software packages. We aimed to quantify the volumetric and spatial agreement between the CTP ischemic core and follow-up infarct for four ischemic core estimation approaches using syngo.via.MethodsWe included successfully reperfused, EVT-treated patients with baseline CTP and 24h follow-up diffusion weighted magnetic resonance imaging (DWI) (November 2017-September 2020). Data were processed with syngo.via VB40 using four core estimation approaches based on: cerebral blood volume (CBV)ResultsIn 59 patients, median estimated CTP core volumes for four core estimation approaches ranged from 12-39 mL. Median 24h follow-up DWI infarct volume was 11 mL. The intraclass correlation coefficient (ICC) showed moderate-good volumetric agreement for all approaches (range 0.61-0.76). Median Dice was low for all approaches (range 0.16-0.21). CTP core overestimation >10mL occurred least frequent (14/59 [24%] patients) using the CBV-based core estimation approach with smoothing filter.ConclusionsIn successfully reperfused patients who underwent EVT, syngo.via CTP ischemic core estimation showed moderate volumetric and spatial agreement with the follow-up infarct on DWI. In patients with complete reperfusion after EVT, the volumetric agreement was excellent. A CTP core estimation approach based on CBV