Objectives
We aimed to evaluate the real-world variation in CT perfusion (CTP) imaging protocols among stroke centers and to explore the potential for standardizing vendor software to harmonize CTP ...images.
Methods
Stroke centers participating in a nationwide multicenter healthcare evaluation were requested to share their CTP scan and processing protocol. The impact of these protocols on CTP imaging was assessed by analyzing data from an anthropomorphic phantom with center-specific vendor software with default settings from one of three vendors (A–C): IntelliSpace Portal, syngoVIA, and Vitrea. Additionally, standardized infarct maps were obtained using a logistic model.
Results
Eighteen scan protocols were studied, all varying in acquisition settings. Of these protocols, seven, eight, and three were analyzed with center-specific vendor software A, B, and C respectively. The perfusion maps were visually dissimilar between the vendor software but were relatively unaffected by the acquisition settings. The median error interquartile range of the infarct core volumes (mL) estimated by the vendor software was − 2.5 6.5 (A)/ − 18.2 1.2 (B)/ − 8.0 1.4 (C) when compared to the ground truth of the phantom (where a positive error indicates overestimation). Taken together, the median error interquartile range of the infarct core volumes (mL) was − 8.2 14.6 before standardization and − 3.1 2.5 after standardization.
Conclusions
CTP imaging protocols varied substantially across different stroke centers, with the perfusion software being the primary source of differences in CTP images. Standardizing the estimation of ischemic regions harmonized these CTP images to a degree.
Clinical relevance statement
The center that a stroke patient is admitted to can influence the patient’s diagnosis extensively. Standardizing vendor software for CT perfusion imaging can improve the consistency and accuracy of results, enabling a more reliable diagnosis and treatment decision.
Key Points
• CT perfusion imaging is widely used for stroke evaluation, but variation in the acquisition and processing protocols between centers could cause varying patient diagnoses.
• Variation in CT perfusion imaging mainly arises from differences in vendor software rather than acquisition settings, but these differences can be reconciled by standardizing the estimation of ischemic regions.
• Standardizing the estimation of ischemic regions can improve CT perfusion imaging for stroke evaluation by facilitating reliable evaluations independent of the admission center.
Objectives
To compare single parameter thresholding with multivariable probabilistic classification of ischemic stroke regions in the analysis of computed tomography perfusion (CTP) parameter maps.
...Methods
Patients were included from two multicenter trials and were divided into two groups based on their modified arterial occlusive lesion grade. CTP parameter maps were generated with three methods—a commercial method (ISP), block-circulant singular value decomposition (bSVD), and non-linear regression (NLR). Follow-up non-contrast CT defined the follow-up infarct region. Conventional thresholds for individual parameter maps were established with a receiver operating characteristic curve analysis. Probabilistic classification was carried out with a logistic regression model combining the available CTP parameters into a single probability.
Results
A total of 225 CTP data sets were included, divided into a group of 166 patients with successful recanalization and 59 with persistent occlusion. The precision and recall of the CTP parameters were lower individually than when combined into a probability. The median difference interquartile range in mL between the estimated and follow-up infarct volume was 29/23/23 52/50/52 (ISP/bSVD/NLR) for conventional thresholding and was 4/6/11 31/25/30 (ISP/bSVD/NLR) for the probabilistic classification.
Conclusions
Multivariable probability maps outperform thresholded CTP parameter maps in estimating the infarct lesion as observed on follow-up non-contrast CT. A multivariable probabilistic approach may harmonize the classification of ischemic stroke regions.
Key Points
•
Combining CTP parameters with a logistic regression model increases the precision and recall in estimating ischemic stroke regions
.
•
Volumes following from a probabilistic analysis predict follow-up infarct volumes better than volumes following from a threshold-based analysis
.
•
A multivariable probabilistic approach may harmonize the classification of ischemic stroke regions
.
Background and Purpose- The volume of estimated ischemic core using computed tomography perfusion (CTP) imaging can identify ischemic stroke patients who are likely to benefit from reperfusion, ...particularly beyond standard time windows. We assessed the accuracy of pretreatment CTP estimated ischemic core in patients with successful endovascular reperfusion. Methods- Patients from the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) and EXTEND-IA TNK (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke) databases who had pretreatment CTP, >50% angiographic reperfusion, and follow-up magnetic resonance imaging at 24 hours were included. Ischemic core volume on baseline CTP data was estimated using relative cerebral blood flow <30% (RAPID, iSchemaView). Follow-up diffusion magnetic resonance imaging was registered to CTP, and the diffusion lesion was outlined using a semiautomated algorithm. Volumetric and spatial agreement (using Dice similarity coefficient, average Hausdorff distance, and precision) was assessed, and expert visual assessment of quality was performed. Results- In 120 patients, median CTP estimated ischemic core volume was 7.8 mL (IQR, 1.8-19.9 mL), and median diffusion lesion volume at 24 hours was 30.8 mL (IQR, 14.9-67.6 mL). Median volumetric difference was 4.4 mL (IQR, 1.2-12.0 mL). Dice similarity coefficient was low (median, 0.24; IQR, 0.15-0.37). The median precision (positive predictive value) of 0.68 (IQR, 0.40-0.88) and average Hausdorff distance (median, 3.1; IQR, 1.8-5.7 mm) indicated reasonable spatial agreement for regions estimated as ischemic core at baseline. Overestimation of total ischemic core volume by CTP was uncommon. Expert visual review revealed overestimation predominantly in white matter regions. Conclusions- CTP estimated ischemic core volumes were substantially smaller than follow-up diffusion-weighted imaging lesions at 24 hours despite endovascular reperfusion within 2 hours of imaging. This may be partly because of infarct growth. Volumetric CTP core overestimation was uncommon and not related to imaging-to-reperfusion time. Core overestimation in white matter should be a focus of future efforts to improve CTP accuracy.
CT perfusion imaging is important in the imaging workup of acute ischemic stroke for evaluating affected cerebral tissue. CT perfusion analysis software produces cerebral perfusion maps from commonly ...noisy spatio-temporal CT perfusion data. High levels of noise can influence the results of CT perfusion analysis, necessitating software tuning. This work proposes a novel approach for CT perfusion analysis that uses physics-informed learning, an optimization framework that is robust to noise. In particular, we propose SPPINN: Spatio-temporal Perfusion Physics-Informed Neural Network and research spatio-temporal physics-informed learning. SPPINN learns implicit neural representations of contrast attenuation in CT perfusion scans using the spatio-temporal coordinates of the data and employs these representations to estimate a continuous representation of the cerebral perfusion parameters. We validate the approach on simulated data to quantify perfusion parameter estimation performance. Furthermore, we apply the method to in-house patient data and the public Ischemic Stroke Lesion Segmentation 2018 benchmark data to assess the correspondence between the perfusion maps and reference standard infarct core segmentations. Our method achieves accurate perfusion parameter estimates even with high noise levels and differentiates healthy tissue from infarcted tissue. Moreover, SPPINN perfusion maps accurately correspond with reference standard infarct core segmentations. Hence, we show that using spatio-temporal physics-informed learning for cerebral perfusion estimation is accurate, even in noisy CT perfusion data. The code for this work is available at https://github.com/lucasdevries/SPPINN.
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•We present SPPINN: A new approach to CT perfusion analysis in acute ischemic stroke.•We use spatio-temporal physics-informed learning with implicit neural representations.•SPPINN is consistent across noise levels and distinguishes healthy/infarcted tissue.•Perfusion maps accurately correspond to reference standard infarct core segmentations.
A larger thrombus in patients with acute ischemic stroke might result in more complex endovascular treatment procedures, resulting in poorer patient outcomes. Current evidence on thrombus volume and ...length related to procedural and functional outcomes remains contradicting. This study aimed to assess the prognostic value of thrombus volume and thrombus length and whether this relationship differs between first-line stent retrievers and aspiration devices for endovascular treatment.
In this multicenter retrospective cohort study, 670 of 3279 patients from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) for endovascularly treated large vessel occlusions were included. Thrombus volume (0.1 mL) and length (0.1 mm) based on manual segmentations and measurements were related to reperfusion grade (expanded Treatment in Cerebral Infarction score) after endovascular treatment, the number of retrieval attempts, symptomatic intracranial hemorrhage, and a shift for functional outcome at 90 days measured with the reverted ordinal modified Rankin Scale (odds ratio >1 implies a favorable outcome). Univariable and multivariable linear and logistic regression were used to report common odds ratios (cORs)/adjusted cOR and regression coefficients (B/aB) with 95% CIs. Furthermore, a multiplicative interaction term was used to analyze the relationship between first-line device choice, stent retrievers versus aspiration device, thrombus volume, and outcomes.
Thrombus volume was associated with functional outcome (adjusted cOR, 0.83 95% CI, 0.71-0.97) and number of retrieval attempts (aB, 0.16 95% CI, 0.16-0.28) but not with the other outcome measures. Thrombus length was only associated with functional independence (adjusted cOR, 0.45 95% CI, 0.24-0.85). Patients with more voluminous thrombi had worse functional outcomes if endovascular treatment was based on first-line stent retrievers (interaction cOR, 0.67 95% CI, 0.50-0.89;
=0.005; adjusted cOR, 0.74 95% CI, 0.55-1.0;
=0.04).
In this study, patients with a more voluminous thrombus required more endovascular thrombus retrieval attempts and had a worse functional outcome. Patients with a lengthier thrombus were less likely to achieve functional independence at 90 days. For more voluminous thrombi, first-line stent retrieval compared with first-line aspiration might be associated with worse functional outcome.
Background
Computed tomography perfusion (CTP) is frequently performed during the diagnostic workup of acute ischemic stroke patients. Yet, ischemic core estimates vary widely between different ...commercially available software packages. We assessed the volumetric and spatial agreement of the ischemic core on CTP with the follow-up infarct on diffusion-weighted imaging (DWI) using an automated software.
Methods
We included successfully reperfused patients who underwent endovascular treatment (EVT) with CTP and follow-up DWI between November 2017 and September 2020. CTP data were processed with a fully automated software using relative cerebral blood flow (rCBF) < 30% to estimate the ischemic core. The follow-up infarct was segmented on DWI imaging data, which were acquired at approximately 24 h. Ischemic core on CTP was compared with the follow-up infarct lesion on DWI using intraclass correlation coefficient (ICC) and Dice similarity coefficient (Dice).
Results
In 59 patients, the median estimated core volume on CTP was 16 (IQR 8–47) mL. The follow-up infarct volume on DWI was 11 (IQR 6–42) mL. ICC was 0.60 (95% CI 0.33–0.76), indicating moderate volumetric agreement. Median Dice was 0.20 (IQR 0.01–0.35). The median positive predictive value was 0.24 (IQR 0.05–0.57), and the median sensitivity was 0.3 (IQR 0.13–0.47). Severe core overestimation on computed tomography perfusion > 50 mL occurred in 4/59 (7%) of the cases.
Conclusions
In patients with successful reperfusion after EVT, CTP-estimated ischemic core showed moderate volumetric and spatial agreement with the follow-up infarct lesion on DWI, similar to the most used commercially available CTP software packages. Severe ischemic core overestimation was relatively uncommon.
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.
Cerebral 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.
Merino-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.
Intracranial pressure and MRI scans were normal in sham animals. Following stroke, ICP rose gradually over time and by 5 days was significantly (
< 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 (
< 0.01), in keeping with increasing ICP. Serum SP levels were significantly elevated (
< 0.01) by 7 days post-tMCAO.
We 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.
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.
Purpose
Recently, multiple randomised controlled trials showed efficacy of endovascular treatment over traditional care in patients with acute ischemic stroke due to an intracranial anterior ...circulation occlusion. Internal carotid artery (ICA) dissection with a concomitant intracranial occlusion is a rare but important cause of severe acute ischemic stroke. Although this subtype of acute ischemic stroke is mostly treated with endovascular treatment, treatment outcomes are still sparsely studied. This study assesses the clinical outcome and reperfusion rates by means of a systematic review.
Methods
Electronic databases of PubMed, EMBASE and Web of Science were searched up to October 1, 2016 for articles describing endovascular treatment in patients with intracranial artery occlusion and ICA dissection.
Results
Sixteen studies were included in the analysis. Most studies showed favourable outcome and successful reperfusion. However, most included studies had a high risk of bias.
Conclusion
In the reviewed studies, endovascular treatment in patients with ICA dissection and concomitant proximal intracranial occlusion was associated with favourable outcome. This could point in the direction of endovascular treatment being a beneficial treatment method for these patients. However, this review has only taken data of a limited group of patients into account. A pooled analysis of patients from recently published endovascular treatment trials and running registries is therefore recommended.
Purpose
Acute stroke patients presenting with a distal internal carotid artery occlusion and patent carotid terminus, allowing for collateral flow via the circle of Willis, may have a more favorable ...natural history. Therefore, benefit of endovascular treatment (EVT) is less evident. We performed an exploratory analysis of EVT results compared to conservative treatment in patients with ‘carotid-I’ occlusions.
Methods
We report on EVT-treated and non-EVT-treated patients with carotid-I occlusions from the MR CLEAN Registry, MR CLEAN trial, and our comprehensive stroke center. CT-angiography was reviewed on primary collateral patency and choroid plexus enhancement. Perfusion deficits were assessed on CT-perfusion (CTP). Clot migration was assessed by comparing clot location on baseline CTA to its location on periprocedural digital subtraction angiography. Outcomes included 90-day functional independence (mRS 0–2), successful reperfusion and mortality.
Results
We included 51 patients. Forty-one patients received EVT, ten patients did not. Intravenous thrombolysis was administered in 32 (78%) EVT-treated patients and 6 (60%) non-EVT-treated patients. CTP, available for 17 patients, showed hypoperfusion on cerebral blood flow maps in 13 (76%) patients. Successful reperfusion after EVT occurred in 23 (56%), and clot migration in 8 patients (20%). Functional independence was achieved in 54% (21/39) of EVT-treated and in 10% (1/10) of non-EVT-treated patients. Mortality was 26% (10/39) and 30% (3/10), respectively. Anterior choroidal artery patency and choroid plexus enhancement were positively associated with functional independence.
Conclusion
In our population, data suggest improved outcomes after EVT in carotid-I occlusion patients and provide no arguments to withhold EVT in these patients.
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