Dr. van Voorst is a postdoctoral scholar in Radiology studying the interfaces of artificial intelligence and neuroradiological imaging in stroke. Originally educated as an MD, Dr. van Voorst gained additional degrees in Finance and Data Science. As a PhD student, Dr. van Voorst focused on cost-effectiveness modeling and developed machine learning and deep learning algorithms with applications in acute ischemic stroke imaging. In his current research, Dr. van Voorst develops artificial intelligence algorithms to automatically extract information from arteries and veins in radiological stroke imaging.
MSc, Vrije Universiteit, Amsterdam, Medicine (2018)
MSc, Universiteit Utrecht, Banking and Finance (2018)
MSc, Universiteit van Amsterdam, MSc Information studies: Data Science track (graduated with honors) (2018)
BSc, Vrije Universiteit, Amsterdam, Medicine (2013)
Jeremy Heit, Postdoctoral Faculty Sponsor
Cost-effectiveness of Direct Transfer to Angiography Suite of Patients With Suspected Large Vessel Occlusion.
2023; 101 (10): e1036-e1045
Patients with acute ischemic stroke due to large vessel occlusion (LVO) deemed eligible for endovascular thrombectomy (EVT) are transferred from the emergency room to the angiography suite to undergo the procedure. Recently, the strategy of direct transfer of patients with suspected LVO to the angiography suite (DTAS) has been shown to improve functional outcomes. This study aims to evaluate the cost-effectiveness of the DTAS strategy vs initial transfer of patients with suspected LVO (Rapid Arterial Occlusion Evaluation score >4 and NIH Stroke Scale >10) to the emergency room (ITER).A decision-analytic Markov model was developed to estimate the cost-effectiveness of the DTAS strategy vs the ITER strategy from a Dutch health care perspective with a 10-year time horizon. The primary outcome was the incremental cost-effectiveness ratio (ICER) using Dutch thresholds of $59,135 (€50,000) and $94,616 (€80,000) per quality-adjusted life year (QALY). Uncertainty of input parameters was assessed using 1-way sensitivity analysis, scenario analysis, and probabilistic sensitivity analysis.The DTAS strategy yielded 0.65 additional QALYs at an additional $16,089, resulting in an ICER of $24,925/QALY compared with the ITER strategy. The ICER varied from $27,169 to $38,325/QALY across different scenarios. The probabilistic sensitivity analysis showed that the DTAS strategy had a 91.8% and 97.0% likelihood of being cost-effective at a decision threshold of $59,135/QALY and $94,616/QALY, respectively.The cost-effectiveness of the DTAS strategy over ITER is robust for patients with suspected LVO. Together with recently published clinical results, this means that implementation of the DTAS strategy may be considered to improve the workflow and outcome of EVT.
View details for DOI 10.1212/WNL.0000000000207583
View details for PubMedID 37438129
Standardizing the estimation of ischemic regions can harmonize CT perfusion stroke imaging
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.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.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.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.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.• 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.
View details for DOI 10.1007/s00330-023-10035-1
View details for Web of Science ID 001047711400004
View details for PubMedID 37572189
View details for PubMedCentralID 6590673
Accuracy of Four Different CT Perfusion Thresholds for Ischemic Core Volume and Location Estimation Using IntelliSpace Portal
JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE
2023; 10 (6)
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.
View details for DOI 10.3390/jcdd10060239
View details for Web of Science ID 001014707000001
View details for PubMedID 37367404
View details for PubMedCentralID PMC10299344
Cost-effectiveness of tenecteplase versus alteplase for acute ischemic stroke
EUROPEAN STROKE JOURNAL
Alteplase is widely used as an intravenous thrombolytic drug in acute ischemic stroke (AIS). Recently however, tenecteplase, a modified form of tissue plasminogen activator, has been shown to increase early recanalization rate and has proven to be non-inferior with a similar safety profile compared to alteplase. This study aims to evaluate the cost-effectiveness of 0.25 mg/kg tenecteplase versus 0.9 mg/kg alteplase for intravenous thrombolysis in AIS patients from the Dutch healthcare payer perspective.A Markov decision-analytic model was constructed to assess total costs, total quality-adjusted life year (QALY), an incremental cost-effectiveness ratio, and incremental net monetary benefit (INMB) of two treatments at willingness-to-pay (WTP) thresholds of €50,000/QALY and €80,000/QALY over a 10-year time horizon. One-way sensitivity analysis, probabilistic sensitivity analysis, and scenario analysis were conducted to test the robustness of results. Clinical data were obtained from large randomized controlled trials and real-world data.Treatment with tenecteplase saved €21 per patient while gaining 0.05 QALYs, resulting in INMB of €2381, clearly rendering tenecteplase cost-effective compared to alteplase. Importantly, tenecteplase remained the cost-effective alternative in all scenarios, including AIS patients due to large vessel occlusion (LVO). Probabilistic sensitivity analysis proved tenecteplase to be cost-effective with a 71.0% probability at a WTP threshold of €50,000/QALY.Tenecteplase treatment was cost-effective for all AIS patients (including AIS patients with LVO) compared to alteplase. The finding supports the broader use of tenecteplase in acute stroke care, as health outcomes improve at acceptable costs while having practical advantages, and a similar safety profile.
View details for DOI 10.1177/23969873231174943
View details for Web of Science ID 001002829200001
View details for PubMedID 37641549
View details for PubMedCentralID PMC10472948
Endovascular treatment versus no endovascular treatment after 6-24 h in patients with ischaemic stroke and collateral flow on CT angiography (MR CLEAN-LATE) in the Netherlands: a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial
2023; 401 (10385): 1371-1380
Endovascular treatment for anterior circulation ischaemic stroke is effective and safe within a 6 h window. MR CLEAN-LATE aimed to assess efficacy and safety of endovascular treatment for patients treated in the late window (6-24 h from symptom onset or last seen well) selected on the basis of the presence of collateral flow on CT angiography (CTA).MR CLEAN-LATE was a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial done in 18 stroke intervention centres in the Netherlands. Patients aged 18 years or older with ischaemic stroke, presenting in the late window with an anterior circulation large-vessel occlusion and collateral flow on CTA, and a neurological deficit score of at least 2 on the National Institutes of Health Stroke Scale were included. Patients who were eligible for late-window endovascular treatment were treated according to national guidelines (based on clinical and perfusion imaging criteria derived from the DAWN and DEFUSE-3 trials) and excluded from MR CLEAN-LATE enrolment. Patients were randomly assigned (1:1) to receive endovascular treatment or no endovascular treatment (control), in addition to best medical treatment. Randomisation was web based, with block sizes ranging from eight to 20, and stratified by centre. The primary outcome was the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included all-cause mortality at 90 days after randomisation and symptomatic intracranial haemorrhage. All randomly assigned patients who provided deferred consent or died before consent could be obtained comprised the modified intention-to-treat population, in which the primary and safety outcomes were assessed. Analyses were adjusted for predefined confounders. Treatment effect was estimated with ordinal logistic regression and reported as an adjusted common odds ratio (OR) with a 95% CI. This trial was registered with the ISRCTN, ISRCTN19922220.Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned, and 502 (94%) patients provided deferred consent or died before consent was obtained (255 in the endovascular treatment group and 247 in the control group; 261 [52%] females). The median mRS score at 90 days was lower in the endovascular treatment group than in the control group (3 [IQR 2-5] vs 4 [2-6]), and we observed a shift towards better outcomes on the mRS for the endovascular treatment group (adjusted common OR 1·67 [95% CI 1·20-2·32]). All-cause mortality did not differ significantly between groups (62 [24%] of 255 patients vs 74 [30%] of 247 patients; adjusted OR 0·72 [95% CI 0·44-1·18]). Symptomatic intracranial haemorrhage occurred more often in the endovascular treatment group than in the control group (17 [7%] vs four [2%]; adjusted OR 4·59 [95% CI 1·49-14·10]).In this study, endovascular treatment was efficacious and safe for patients with ischaemic stroke caused by an anterior circulation large-vessel occlusion who presented 6-24 h from onset or last seen well, and who were selected on the basis of the presence of collateral flow on CTA. Selection of patients for endovascular treatment in the late window could be primarily based on the presence of collateral flow.Collaboration for New Treatments of Acute Stroke consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Top Sector Life Sciences & Health, and the Netherlands Brain Foundation.
View details for DOI 10.1016/S0140-6736(23)00575-5
View details for Web of Science ID 000999272700001
View details for PubMedID 37003289
Role of intravenous alteplase on late lesion growth and clinical outcome after stroke treatment
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Several acute ischemic stroke mechanisms that cause lesion growth continue after treatment which is detrimental to long-term clinical outcome. The potential role of intravenous alteplase treatment (IVT), a standard in stroke care, in cessing the physiological processes causing post-treatment lesion development is understudied. We analyzed patients from the MR CLEAN-NO IV trial with good quality 24-hour and 1-week follow-up Non-Contrast CT scans. We delineated hypo- and hyper-dense regions on the scans as lesion. We performed univariable logistic and linear regression to estimate the influence of IVT on the presence (growth > 0 ml) and extent of late lesion growth. The association between late lesion growth and mRS was assessed using ordinal logistic regression. Interaction analysis was performed to evaluate the influence of IVT on this association. Of the 63/116 were randomized to included patients, IVT. Median growth was 8.4(-0.88-26) ml. IVT was not significantly associated with the presence (OR: 1.24 (0.57-2.74, p = 0.59) or extent (β = 5.1(-8.8-19), p = 0.47) of growth. Late lesion growth was associated with worse clinical outcome (aOR: 0.85(0.76-0.95), p < 0.01; per 10 ml). IVT did not influence this association (p = 0.18). We did not find evidence that IVT influences late lesion growth or the relationship between growth and worse clinical outcome. Therapies to reduce lesion development are necessary.
View details for DOI 10.1177/0271678X231167755
View details for Web of Science ID 000963793400001
View details for PubMedID 37017421
Prognostic Value of Thrombus Volume and Interaction With First-Line Endovascular Treatment Device Choice
2023; 54 (4): 1056-1065
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]; P=0.005; adjusted cOR, 0.74 [95% CI, 0.55-1.0]; P=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.
View details for DOI 10.1161/STROKEAHA.122.041606
View details for Web of Science ID 000968172400040
View details for PubMedID 36912141
Infarct Evolution in Patients with Anterior Circulation Large-Vessel Occlusion Randomized to IV Alteplase and Endovascular Treatment versus Endovascular Treatment Alone
AMERICAN JOURNAL OF NEURORADIOLOGY
Infarct evolution after endovascular treatment varies widely among patients with stroke and may be affected by baseline characteristics and procedural outcomes. Moreover, IV alteplase and endovascular treatment may influence the relationship of these factors to infarct evolution. We aimed to assess whether the infarct evolution between baseline and follow-up imaging was different for patients who received IVT and EVT versus EVT alone.We included patients from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN)-NO IV trial with baseline CTP and follow-up imaging. Follow-up infarct volume was segmented on 24-hour or 1-week follow-up DWI or NCCT. Infarct evolution was defined as the follow-up lesion volume: CTP core volume. Substantial infarct growth was defined as an increase in follow-up infarct volume of >10 mL. We assessed whether infarct evolution was different for patients with IV alteplase and endovascular treatment versus endovascular treatment alone and evaluated the association of baseline characteristics and procedural outcomes with infarct evolution using multivariable regression.From 228 patients with CTP results available, 145 patients had follow-up imaging and were included in our analysis. For patients with IV alteplase and endovascular treatment versus endovascular treatment alone, the baseline median CTP core volume was 17 (interquartile range = 4-35) mL versus 11 (interquartile range = 6-24) mL. The median follow-up infarct volume was 13 (interquartile range, 4-48) mL versus 17 (interquartile range = 4-50) mL. Collateral status and occlusion location were negatively associated with substantial infarct growth in patients with and without IV alteplase before endovascular treatment.No statistically significant difference in infarct evolution was found in directly admitted patients who received IV alteplase and endovascular treatment within 4.5 hours of symptom onset versus patients who underwent endovascular treatment alone. Collateral status and occlusion location may be useful predictors of infarct evolution prognosis in patients eligible for IV alteplase who underwent endovascular treatment.
View details for DOI 10.3174/ajnr.A7826
View details for Web of Science ID 000957854600001
View details for PubMedID 36958803
View details for PubMedCentralID PMC10084906
Association between computed tomography perfusion and the effect of intravenous alteplase prior to endovascular treatment in acute ischemic stroke
Intravenous alteplase (IVT) prior to endovascular treatment (EVT) is neither superior nor noninferior to EVT alone in acute ischemic stroke patients. We aim to assess whether the effect of IVT prior to EVT differs according to CT perfusion (CTP)-based imaging parameters.In this retrospective post hoc analysis, we included patients from the MR CLEAN-NO IV with available CTP data. CTP data were processed using syngo.via (version VB40). We performed multivariable logistic regression to obtain the effect size estimates (adjusted common odds ratio a[c]OR) on 90-day functional outcome (modified Rankin Scale [mRS]) and functional independence (mRS 0-2) for CTP parameters with two-way multiplicative interaction terms between IVT administration and the studied parameters.In 227 patients, median CTP-estimated core volume was 13 (IQR 5-35) mL. The treatment effect of IVT prior to EVT on outcome was not altered by CTP-estimated ischemic core volume, penumbral volume, mismatch ratio, and presence of a target mismatch profile. None of the CTP parameters was significantly associated with functional outcome after adjusting for confounders.In directly admitted patients with limited CTP-estimated ischemic core volumes who presented within 4.5 h after symptom onset, CTP parameters did not statistically significantly alter the treatment effect of IVT prior to EVT. Further studies are needed to confirm these results in patients with larger core volumes and more unfavorable baseline perfusion profiles on CTP imaging.
View details for DOI 10.1007/s00234-023-03139-4
View details for Web of Science ID 000945791100001
View details for PubMedID 36884080
View details for PubMedCentralID PMC10169898
Agreement between estimated computed tomography perfusion ischemic core and follow-up infarct on diffusion-weighted imaging
INSIGHTS INTO IMAGING
2022; 13 (1): 191
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.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).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.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.
View details for DOI 10.1186/s13244-022-01334-0
View details for Web of Science ID 000898878500003
View details for PubMedID 36512159
View details for PubMedCentralID PMC9748002
Type of intracranial hemorrhage after endovascular stroke treatment: association with functional outcome
JOURNAL OF NEUROINTERVENTIONAL SURGERY
Intracranial hemorrhage (ICH) is a frequent complication after endovascular stroke treatment.To assess the association of the occurrence and type of ICH after endovascular treatment (EVT) with functional outcome.We analyzed data from the MR CLEAN-NO IV and MR CLEAN-MED trials. Both trials included adult patients with ischemic stroke with a large vessel occlusion in the anterior circulation, who were eligible for EVT. ICH was classified (1) as asymptomatic or symptomatic (concomitant neurological deterioration of ≥4 points on the NIHSS, or ≥2 points on 1 NIHSS item), and (2) according to the Heidelberg Bleeding Classification. We used multivariable ordinal logistic regression analyses to assess the association of the occurrence and type of ICH with the modified Rankin Scale score at 90 days.Of 1017 included patients, 331 (33%) had an asymptomatic ICH, and 90 (9%) had a symptomatic ICH. Compared with no ICH, both asymptomatic (adjusted common OR (acOR)=0.76; 95% CI 0.58 to 0.98) and symptomatic (acOR=0.07; 95% CI 0.04 to 0.14) ICH were associated with worse functional outcome. In particular, isolated parenchymal hematoma type 2 (acOR=0.37; 95% CI 0.14 to 0.95), combined parenchymal hematoma with hemorrhage outside infarcted brain tissue (acOR=0.17; 95% CI 0.10 to 0.30), and combined hemorrhages outside infarcted brain tissue (acOR=0.14; 95% CI 0.03 to 0.74) were associated with worse functional outcome than no ICH.Strength of the association of ICH with functional outcome depends on the type of ICH. Although the association is stronger for symptomatic ICH, asymptomatic ICH after EVT is also associated with worse functional outcome.
View details for DOI 10.1136/jnis-2022-019474
View details for Web of Science ID 000870710100001
View details for PubMedID 36261280
Safety and efficacy of periprocedural antithrombotics in patients with successful reperfusion after endovascular stroke treatment
JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
2022; 31 (10): 106726
We aimed to evaluate whether the overall harmful effect of periprocedural treatment with aspirin or heparin during endovascular stroke treatment is different in patients with a successful reperfusion after the procedure.We performed a post-hoc analysis of the MR CLEAN-MED trial, including adult patients with a large vessel occlusion in the anterior circulation eligible for endovascular treatment (EVT). In this trial, patients were randomized for periprocedural intravenous treatment with aspirin or no aspirin (1:1 ratio), and for moderate-dose unfractionated heparin, low-dose unfractionated heparin or no unfractionated heparin (1:1:1 ratio). We tested for interaction between the post-EVT extended thrombolysis in cerebral infarction (eTICI) score and treatment with periprocedural medication with multivariable regression analyses. The primary outcome was the modified Rankin Scale score at 90 days. Secondary outcomes were final infarct volume, intracranial hemorrhage, and symptomatic intracranial hemorrhage.Of 534 included patients, 93 (17%) had a post-EVT eTICI score of 0-2a, 115 (22%) a score of 2b, 73 (14%) a score of 2c, and 253 (47%) a score of 3. For both aspirin and heparin, we found no interaction between post-EVT eTICI score and treatment on the modified Rankin Scale score (p=0.76 and p=0.47, respectively). We found an interaction between post-EVT eTICI score and treatment with heparin on the final infarct volume (p=0.01). Of note, this interaction showed a biologically implausible distribution over the subgroups.The overall harmful effect of periprocedural aspirin and unfractionated heparin is not different in patients with a successful reperfusion after EVT.
View details for DOI 10.1016/j.jstrokecerebrovasdis.2022.106726
View details for Web of Science ID 000864176400012
View details for PubMedID 36029687
Outcome Prediction Based on Automatically Extracted Infarct Core Image Features in Patients with Acute Ischemic Stroke
2022; 12 (8)
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.
View details for DOI 10.3390/diagnostics12081786
View details for Web of Science ID 000846984900001
View details for PubMedID 35892499
View details for PubMedCentralID PMC9331690
Unsupervised Deep Learning for Stroke Lesion Segmentation on Follow-up CT Based on Generative Adversarial Networks.
AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Supervised deep learning is the state-of-the-art method for stroke lesion segmentation on NCCT. Supervised methods require manual lesion annotations for model development, while unsupervised deep learning methods such as generative adversarial networks do not. The aim of this study was to develop and evaluate a generative adversarial network to segment infarct and hemorrhagic stroke lesions on follow-up NCCT scans.MATERIALS AND METHODS: Training data consisted of 820 patients with baseline and follow-up NCCT from 3 Dutch acute ischemic stroke trials. A generative adversarial network was optimized to transform a follow-up scan with a lesion to a generated baseline scan without a lesion by generating a difference map that was subtracted from the follow-up scan. The generated difference map was used to automatically extract lesion segmentations. Segmentation of primary hemorrhagic lesions, hemorrhagic transformation of ischemic stroke, and 24-hour and 1-week follow-up infarct lesions were evaluated relative to expert annotations with the Dice similarity coefficient, Bland-Altman analysis, and intraclass correlation coefficient.RESULTS: The median Dice similarity coefficient was 0.31 (interquartile range, 0.08-0.59) and 0.59 (interquartile range, 0.29-0.74) for the 24-hour and 1-week infarct lesions, respectively. A much lower Dice similarity coefficient was measured for hemorrhagic transformation (median, 0.02; interquartile range, 0-0.14) and primary hemorrhage lesions (median, 0.08; interquartile range, 0.01-0.35). Predicted lesion volume and the intraclass correlation coefficient were good for the 24-hour (bias, 3 mL; limits of agreement, -64-59mL; intraclass correlation coefficient, 0.83; 95% CI, 0.78-0.88) and excellent for the 1-week (bias, -4 m; limits of agreement,-66-58 mL; intraclass correlation coefficient, 0.90; 95% CI, 0.83-0.93) follow-up infarct lesions.CONCLUSIONS: An unsupervised generative adversarial network can be used to obtain automated infarct lesion segmentations with a moderate Dice similarity coefficient and good volumetric correspondence.
View details for DOI 10.3174/ajnr.A7582
View details for PubMedID 35902122
Thrombus radiomics in patients with anterior circulation acute ischemic stroke undergoing endovascular treatment
JOURNAL OF NEUROINTERVENTIONAL SURGERY
Thrombus radiomics (TR) describe complex shape and textural thrombus imaging features. We aimed to study the relationship of TR extracted from non-contrast CT with procedural and functional outcome in endovascular-treated patients with acute ischemic stroke.Thrombi were segmented on thin-slice non-contrast CT (≤1 mm) from 699 patients included in the MR CLEAN Registry. In a pilot study, we selected 51 TR with consistent values across two raters' segmentations (ICC >0.75). Random forest models using TR in addition or as a substitute to baseline clinical variables (CV) and manual thrombus measurements (MTM) were trained with 499 patients and evaluated on 200 patients for predicting successful reperfusion (extended Thrombolysis in Cerebral Ischemia (eTICI) ≥2B), first attempt reperfusion, reperfusion within three attempts, and functional independence (modified Rankin Scale (mRS) ≤2). Three texture and shape features were selected based on feature importance and related to eTICI ≥2B, number of attempts to eTICI ≥2B, and 90-day mRS with ordinal logistic regression.Random forest models using TR, CV or MTM had comparable predictive performance. Thrombus texture (inverse difference moment normalized) was independently associated with reperfusion (adjusted common OR (acOR) 0.85, 95% CI 0.72 to 0.99). Thrombus volume and texture were also independently associated with the number of attempts to successful reperfusion (acOR 1.36, 95% CI 1.03 to 1.88 and acOR 1.24, 95% CI 1.04 to 1.49).TR describing thrombus volume and texture were associated with more attempts to successful reperfusion. Compared with models using CV and MTM, TR had no added value for predicting procedural and functional outcome.
View details for DOI 10.1136/jnis-2022-019085
View details for Web of Science ID 000831303200001
View details for PubMedID 35882552
Cost-effectiveness of CT perfusion for patients with acute ischemic stroke (CLEOPATRA)-Study protocol for a healthcare evaluation study
EUROPEAN STROKE JOURNAL
2022; 7 (2): 188-197
Computed tomography perfusion (CTP) is variably considered to assess eligibility for endovascular thrombectomy (EVT) in acute ischemic (AIS) stroke patients. Although CTP is recommended for patient selection in later (6-24 h) time window, it is currently not recommended in the earlier (0-6 h) time window and the costs and health effects of including CTP for EVT selection remain unknown. We aim to estimate the costs and health effects of using CTP for EVT selection in AIS patients compared to conventional selection.CLEOPATRA is a healthcare evaluation study using clinical and imaging data from multiple, prospective EVT trials and registries in both the earlier and later time windows. To study the long-term health and cost effects, we will construct a ("Markov") health state transition model simulating the clinical outcome over a 5-year follow-up period for CTP-based and conventional selection for EVT. Clinical data acquired within the current study and estimates from the literature will be used as input for probabilities of events, costs, and Quality-Adjusted Life Years (QALYs) per modified Rankin Scale (mRS) subscore. Primary outcome for the cost-effectiveness analysis will be the Incremental Cost-Effectiveness Ratio (ICER) in terms of costs per QALY gained over the simulated follow-up period.Outcome measures will be reported as cumulative values over a 5-year follow-up period.This study will provide preliminary insight into costs and health effects of including CTP in the selection for EVT for AIS patients, presenting between 0 and 24 h after time last known well. The results may be used to develop recommendations and inform further implementation projects and studies.
View details for DOI 10.1177/23969873221092535
View details for Web of Science ID 000787353400001
View details for PubMedID 35647320
View details for PubMedCentralID PMC9134782
Bifurcation occlusions and endovascular treatment outcome in acute ischemic stroke
JOURNAL OF NEUROINTERVENTIONAL SURGERY
2023; 15 (4): 355-362
A thrombus in the M1 segment of the middle cerebral artery (MCA) can occlude this main stem only or extend into the M1-M2 bifurcation. The occlusion pattern may affect endovascular treatment (EVT) success, as a bifurcated thrombus may be more prone to fragmentation during retrieval.To investigate whether bifurcated thrombus patterns are associated with EVT procedural and clinical outcomes.Occlusion patterns of MCA thrombi on CT angiography from MR CLEAN Registry patients were classified into three groups: main stem occlusion, bifurcation occlusion extending into one M2 branch, and bifurcation occlusion extending into both M2 branches. Procedural parameters, procedural outcomes (reperfusion grade and embolization to new territory), and clinical outcomes (24-48 hour National Institutes of Health Stroke Scale [NIHSSFU] score, change in NIHSS scores between 24 and 48 hours and baseline ∆ [NIHSS], and 90-day modified Rankin Scale [mRS] scores) were compared between occlusion patterns.We identified 1023 patients with an MCA occlusion of whom 370 (36%) had a main stem occlusion, 151 (15%) a single branch, and 502 (49%) a double branch bifurcation occlusion. There were no statistically significant differences in retrieval method, procedure time, number of retrieval attempts, reperfusion grade, and embolization to new territory between occlusion patterns. Patients with main stem occlusions had lower NIHSSFU scores than patients with single (7 vs 11, p=0.01) or double branch occlusions (7 vs 9, p=0.04). However, there were no statistically significant differences in ∆ NIHSS or in 90-day mRS scores.In our population, EVT procedural and long-term clinical outcomes were similar for MCA bifurcation occlusions and MCA main stem occlusions.
View details for DOI 10.1136/neurintsurg-2021-018560
View details for Web of Science ID 000772408200001
View details for PubMedID 35318957
View details for PubMedCentralID PMC10086510
Safety and efficacy of aspirin, unfractionated heparin, both, or neither during endovascular stroke treatment (MR CLEAN-MED): an open-label, multicentre, randomised controlled trial
2022; 399 (10329): 1059-1069
Aspirin and unfractionated heparin are often used during endovascular stroke treatment to improve reperfusion and outcomes. However, the effects and risks of anti-thrombotics for this indication are unknown. We therefore aimed to assess the safety and efficacy of intravenous aspirin, unfractionated heparin, both, or neither started during endovascular treatment in patients with ischaemic stroke.We did an open-label, multicentre, randomised controlled trial with a 2 × 3 factorial design in 15 centres in the Netherlands. We enrolled adult patients (ie, ≥18 years) with ischaemic stroke due to an intracranial large-vessel occlusion in the anterior circulation in whom endovascular treatment could be initiated within 6 h of symptom onset. Eligible patients had a score of 2 or more on the National Institutes of Health Stroke Scale, and a CT or MRI ruling out intracranial haemorrhage. Randomisation was done using a web-based procedure with permuted blocks and stratified by centre. Patients were randomly assigned (1:1) to receive either periprocedural intravenous aspirin (300 mg bolus) or no aspirin, and randomly assigned (1:1:1) to receive moderate-dose unfractionated heparin (5000 IU bolus followed by 1250 IU/h for 6 h), low-dose unfractionated heparin (5000 IU bolus followed by 500 IU/h for 6 h), or no unfractionated heparin. The primary outcome was the score on the modified Rankin Scale at 90 days. Symptomatic intracranial haemorrhage was the main safety outcome. Analyses were based on intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. This trial is registered with the International Standard Randomised Controlled Trial Number, ISRCTN76741621.Between Jan 22, 2018, and Jan 27, 2021, we randomly assigned 663 patients; of whom, 628 (95%) provided deferred consent or died before consent could be asked and were included in the modified intention-to-treat population. On Feb 4, 2021, after unblinding and analysis of the data, the trial steering committee permanently stopped patient recruitment and the trial was stopped for safety concerns. The risk of symptomatic intracranial haemorrhage was higher in patients allocated to receive aspirin than in those not receiving aspirin (43 [14%] of 310 vs 23 [7%] of 318; adjusted OR 1·95 [95% CI 1·13-3·35]) as well as in patients allocated to receive unfractionated heparin than in those not receiving unfractionated heparin (44 [13%] of 332 vs 22 [7%] of 296; 1·98 [1·14-3·46]). Both aspirin (adjusted common OR 0·91 [95% CI 0·69-1·21]) and unfractionated heparin (0·81 [0·61-1·08]) led to a non-significant shift towards worse modified Rankin Scale scores.Periprocedural intravenous aspirin and unfractionated heparin during endovascular stroke treatment are both associated with an increased risk of symptomatic intracranial haemorrhage without evidence for a beneficial effect on functional outcome.The Collaboration for New Treatments of Acute Stroke consortium, the Brain Foundation Netherlands, the Ministry of Economic Affairs, Stryker, Medtronic, Cerenovus, and the Dutch Heart Foundation.
View details for DOI 10.1016/S0140-6736(22)00014-9
View details for Web of Science ID 000768227500025
View details for PubMedID 35240044
Fully Automated Thrombus Segmentation on CT Images of Patients with Acute Ischemic Stroke
2022; 12 (3)
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.
View details for DOI 10.3390/diagnostics12030698
View details for Web of Science ID 000775406600001
View details for PubMedID 35328251
View details for PubMedCentralID PMC8947334
Accuracy of CT perfusion ischemic core volume and location estimation: A comparison between four ischemic core estimation approaches using syngo.via
2022; 17 (8): e0272276
Computed 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.We 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)<1.2mL/100mL with and without smoothing filter, relative cerebral blood flow (rCBF)<30%, and rCBF<20%. The follow-up infarct was segmented on DWI.In 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.In 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<1.2 mL/100mL with smoothing filter least often overestimated the follow-up infarct volume and is therefore preferred for clinical decision making using syngo.via.
View details for DOI 10.1371/journal.pone.0272276
View details for Web of Science ID 000837840000008
View details for PubMedID 35917382
View details for PubMedCentralID PMC9345340
Quantified health and cost effects of faster endovascular treatment for large vessel ischemic stroke patients in the Netherlands
JOURNAL OF NEUROINTERVENTIONAL SURGERY
2021; 13 (12): 1099-+
The effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stroke severely depends on time to treatment. However, it remains unclear what the value of faster treatment is in the years after index stroke. The aim of this study was to quantify the value of faster EVT in terms of health and healthcare costs for the Dutch LVO stroke population.A Markov model was used to simulate 5-year follow-up functional outcome, measured with the modified Rankin Scale (mRS), of 69-year-old LVO patients. Post-treatment mRS was extracted from the MR CLEAN Registry (n=2892): costs per unit of time and Quality-Adjusted Life Years (QALYs) per mRS sub-score were retrieved from follow-up data of the MR CLEAN trial (n=500). Net Monetary Benefit (NMB) at a willingness to pay of €80 000 per QALY was reported as primary outcome, and secondary outcome measures were days of disability-free life gained and costs.EVT administered 1 min faster resulted in a median NMB of €309 (IQR: 226;389), 1.3 days of additional disability-free life (IQR: 1.0;1.6), while cumulative costs remained largely unchanged (median: -€15, IQR: -65;33) over a 5-year follow-up period. As costs over the follow-up period remained stable while QALYs decreased with longer time to treatment, which this results in a near-linear decrease of NMB. Since patients with faster EVT lived longer, they incurred more healthcare costs.One-minute faster EVT increases QALYs while cumulative costs remain largely unaffected. Therefore, faster EVT provides better value of care at no extra healthcare costs.
View details for DOI 10.1136/neurintsurg-2020-017017
View details for Web of Science ID 000722239300007
View details for PubMedID 33479037
View details for PubMedCentralID PMC8606465
A Randomized Trial of Intravenous Alteplase before Endovascular Treatment for Stroke
NEW ENGLAND JOURNAL OF MEDICINE
2021; 385 (20): 1833-1844
The value of administering intravenous alteplase before endovascular treatment (EVT) for acute ischemic stroke has not been studied extensively, particularly in non-Asian populations.We performed an open-label, multicenter, randomized trial in Europe involving patients with stroke who presented directly to a hospital that was capable of providing EVT and who were eligible for intravenous alteplase and EVT. Patients were randomly assigned in a 1:1 ratio to receive EVT alone or intravenous alteplase followed by EVT (the standard of care). The primary end point was functional outcome on the modified Rankin scale (range, 0 [no disability] to 6 [death]) at 90 days. We assessed the superiority of EVT alone over alteplase plus EVT, as well as noninferiority by a margin of 0.8 for the lower boundary of the 95% confidence interval for the odds ratio of the two trial groups. Death from any cause and symptomatic intracerebral hemorrhage were the main safety end points.The analysis included 539 patients. The median score on the modified Rankin scale at 90 days was 3 (interquartile range, 2 to 5) with EVT alone and 2 (interquartile range, 2 to 5) with alteplase plus EVT. The adjusted common odds ratio was 0.84 (95% confidence interval [CI], 0.62 to 1.15; P = 0.28), which showed neither superiority nor noninferiority of EVT alone. Mortality was 20.5% with EVT alone and 15.8% with alteplase plus EVT (adjusted odds ratio, 1.39; 95% CI, 0.84 to 2.30). Symptomatic intracerebral hemorrhage occurred in 5.9% and 5.3% of the patients in the respective groups (adjusted odds ratio, 1.30; 95% CI, 0.60 to 2.81).In a randomized trial involving European patients, EVT alone was neither superior nor noninferior to intravenous alteplase followed by EVT with regard to disability outcome at 90 days after stroke. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by the Collaboration for New Treatments of Acute Stroke consortium and others; MR CLEAN-NO IV ISRCTN number, ISRCTN80619088.).
View details for DOI 10.1056/NEJMoa2107727
View details for Web of Science ID 000724699600010
View details for PubMedID 34758251
Posttreatment Ischemic Lesion Evolution Is Associated With Reduced Favorable Functional Outcome in Patients With Stroke
2021; 52 (11): 3523-3531
Ischemic lesion volume can increase even 24 hours after onset of an acute ischemic stroke. In this study, we investigated the association of lesion evolution with functional outcome and the influence of successful recanalization on this association.We included patients from the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) who received good quality noncontrast CT images 24 hours and 1 week after stroke onset. The ischemic lesion delineations included infarct, edema, and hemorrhagic transformation. Lesion evolution was defined as the difference between the volumes measured on the 1-week and 24-hour noncontrast CTs. The association of lesion evolution with functional outcome was evaluated using unadjusted and adjusted logistic regression. Adjustments were made for baseline, clinical, and imaging parameters that were associated P<0.10) in univariate analysis with favorable functional outcome, defined as modified Rankin Scale score of ≤2. Interaction analysis was performed to evaluate the influence of successful recanalization, defined as modified Arterial Occlusion Lesion score of 3 points, on this association.Of the 226 patients who were included, 69 (31%) patients achieved the favorable functional outcome. Median lesion evolution was 22 (interquartile range, 10–45) mL. Lesion evolution was significantly inversely correlated with favourable functional outcome: unadjusted odds ratio, 0.76 (95% CI, 0.66–0.86; per 10 mL of lesion evolution; P<0.01) and adjusted odds ratio: 0.85 (95% CI, 0.72–0.97; per 10 mL of lesion evolution; P=0.03). There was no significant interaction of successful recanalization on the association of lesion evolution and favorable functional outcome (odds ratio, 1.01 [95% CI, 0.77–1.36]; P=0.94).In our population, subacute ischemic lesion evolution is associated with unfavorable functional outcome. This study suggests that even 24 hours after onset of stroke, deterioration of the brain continues, which has a negative effect on functional outcome. This finding may warrant additional treatment in the subacute phase.
View details for DOI 10.1161/STROKEAHA.120.032331
View details for Web of Science ID 000710623500032
View details for PubMedID 34289708
Cost and health effects of case management compared with outpatient clinic follow-up in a Dutch heart failure cohort
ESC HEART FAILURE
2020; 7 (3): 1136-1144
Heart failure reduces quality of life and life expectancy; hospital admissions are frequent and create a burden on public resources. This study aims to quantify the benefits in terms of health effects [quality-adjusted life years (QALYs)] and costs when heart failure patients receive case management at home compared with outpatient cardiology clinic follow-up.A health state transition (Markov) model was written, and transition probabilities were derived from a cohort of 1114 patients and available literature. QALYs in different health states of heart failure patients were retrieved from the literature, and costs were estimated with data from the financial department of the Noordwest Ziekenhuisgroep and public cost sources. Monthly simulation cycles were repeated 60 times to generate 5 years of virtual follow-up data. Baseline willingness to pay is assumed €50 000 per QALY. Sensitivity analyses were performed in a one-way deterministic and a multiway probabilistic approach; the probabilistic approach used uniform and more plausible distributions of the model parameters. Case management reduced costs by €382 and increased QALYs by 0.261 for the baseline simulation; this results in a net monetary benefit of €13 428. Probabilistic sensitivity analysis based on uniform and most plausible distributions of parameters resulted in 96.2% and 83.3% of the simulations, favouring a treatment strategy of case management.Case management is cost effective in 83.3% of the probabilistic simulations and has a tendency towards reducing costs and increasing QALYs when considering a real-world cohort of heart failure patients in the Netherlands.
View details for DOI 10.1002/ehf2.12692
View details for Web of Science ID 000536512400044
View details for PubMedID 32301235
View details for PubMedCentralID PMC7261554