•Prediction of the final infarct volume in acute ischemic stroke patients.•Takes into account the baseline CTP images and the time and treatment parameters.•Convolutional neural network trained and ...validated on a multicenter dataset.•Operates on the native CTP measurements without explicit deconvolution.•Improved performance over classical approach.
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CT Perfusion (CTP) imaging has gained importance in the diagnosis of acute stroke. Conventional perfusion analysis performs a deconvolution of the measurements and thresholds the perfusion parameters to determine the tissue status. We pursue a data-driven and deconvolution-free approach, where a deep neural network learns to predict the final infarct volume directly from the native CTP images and metadata such as the time parameters and treatment. This would allow clinicians to simulate various treatments and gain insight into predicted tissue status over time. We demonstrate on a multicenter dataset that our approach is able to predict the final infarct and effectively uses the metadata. An ablation study shows that using the native CTP measurements instead of the deconvolved measurements improves the prediction.
Thrombus perviousness is strongly associated with functional outcome and intravenous alteplase treatment success in patients with acute ischemic stroke. Accuracy of thrombus attenuation increase ...(TAI) assessment may be compromised by a heterogeneous thrombus composition and interobserver variations of currently used manual measurements. We hypothesized that TAI is more strongly associated with clinical outcomes when evaluated on the entire thrombus.
In 195 patients, five TAI measures were performed: one manual by placing three regions of interest (TAImanual) and four automated ones assessing densities from the entire thrombus. The automated TAI measures were calculated by comparing quartiles; Q1, Q2, and Q3 of the non-contrast and contrast enhanced thrombus density distribution and using the lag of the maximum of the cross correlations (MCC). Associations with functional outcome (mRS at 90 days) were assessed with univariate and multivariable analyses.
All entire TAI measures were significantly associated with functional outcome with odd ratios (OR) of 1.63(95 %CI:1.19–2.25, p = 0.003) for Q1, 1.56(95 %CI:1.16–2.10, p = 0.003) for Q2, 1.24(95 %CI:1.00–1.54, p = 0.045) for Q3, and 1.70(95 %CI:1.24–2.34, p = 0.001) for MCC per 10 HU increase in univariate models. TAImanual was not significantly associated with functional outcome (p = 0.055). In the multivariable logistic regression models including age, NIHSS, and recanalization, only TAI measures derived from the entire thrombus were independently associated with favorable outcome; OR of 1.64(95 %CI:1.01–2.66, p = 0.048) for Q2 and 1.82(1.13–2.95, p = 0.014) for MCC per 10 HU increase of thrombus attenuation.
The novel perviousness measures of the entire thrombus are more strongly associated with functional outcome than the traditional manual perviousness assessments.
BACKGROUND AND PURPOSE—Thrombus characteristics and collateral score are associated with functional outcome in patients with acute ischemic stroke. It has been suggested that they affect each other. ...The aim of this study is to evaluate the association between clot burden score, thrombus perviousness, and collateral score and to determine whether collateral score influences the association of thrombus characteristics with functional outcome.
METHODS—Patients with baseline thin-slice noncontrast computed tomography and computed tomographic angiography images from the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands) were included (n=195). Collateral score and clot burden scores were determined on baseline computed tomographic angiography. Thrombus attenuation increase was determined by comparing thrombus density on noncontrast computed tomography and computed tomographic angiography using a semiautomated method. The association of collateral score with clot burden score and thrombus attenuation increase was evaluated with linear regression. Mediation and effect modification analyses were used to assess the influence of collateral score on the association of clot burden score and thrombus attenuation increase with functional outcome.
RESULTS—A higher clot burden score (B=0.063; 95% confidence interval, 0.008–0.118) and a higher thrombus attenuation increase (B=0.014; 95% confidence interval, 0.003–0.026) were associated with higher collateral score. Collateral score mediated the association of clot burden score with functional outcome. The association between thrombus attenuation increase and functional outcome was modified by the collateral score, and this association was stronger in patients with moderate and good collaterals.
CONCLUSIONS—Patients with lower thrombus burden and higher thrombus perviousness scores had higher collateral score. The positive effect of thrombus perviousness on clinical outcome was only present in patients with moderate and high collateral scores.
CLINICAL TRIAL REGISTRATION—URLhttp://www.trialregister.nl. Unique identifierNTR1804 and URLhttp://www.controlled-trials.com Unique identifierISRCTN10888758.
Introduction and Aim:
Hemorrhagic transformation (HT) frequently occurs after acute ischemic stroke and negatively influences the functional outcome. Usually, HT is classified by its radiological ...appearance. Discriminating between the subtypes can be complicated, and interobserver variation is considerable. Therefore, we aim to quantify rather than classify hemorrhage volumes and determine the association of hemorrhage volume with functional outcome in comparison with the European Cooperative Acute Stroke Study II classification.
Patients and Methods:
We included patients from the MR CLEAN trial with follow-up imaging. Hemorrhage volume was estimated by manual delineation of the lesion, and HT was classified according to the European Cooperative Acute Stroke Study II classification petechial hemorrhagic infarction types 1 (HI1) and 2 (HI2) and parenchymal hematoma types 1 (PH1) and 2 (PH2) on follow-up CT 24 h to 2 weeks after treatment. We assessed functional outcome using the modified Rankin Scale 90 days after stroke onset. Ordinal logistic regression with and without adjustment for potential confounders was used to describe the association of hemorrhage volume with functional outcome. We created regression models including and excluding total lesion volume as a confounder.
Results:
We included 478 patients. Of these patients, 222 had HT. Median hemorrhage volume was 3.37 ml (0.80–12.6) and per HT subgroup; HI1: 0.2 (0.0–1.7), HI2: 3.2 (1.7–6.1), PH1: 6.3 (4.2–13), and PH2: 47 (19–101). Hemorrhage volume was associated with functional outcome adjusted common odds ratio (acOR): 0.83, 95% CI: 0.73–0.95 but not anymore after adjustment for total lesion volume (acOR: 0.99, 95% CI: 0.86–1.15, per 10 ml). Hemorrhage volume in patients with PH2 was significantly associated with functional outcome after adjusting total lesion volume (acOR: 0.70, 95% CI: 0.50–0.98).
Conclusion:
HT volume is associated with functional outcomes in patients with acute ischemic stroke but not independent of total lesion volume. The extent of a PH2 was associated with outcome, suggesting that measuring hemorrhage volume only provides an additional benefit in the prediction of the outcome when a PH2 is present.
Summary Background Whether infarct size modifies intra-arterial treatment effect is not certain, particularly in patients with large infarcts. We examined the effect of the baseline Alberta Stroke ...Program Early CT Score (ASPECTS) on the safety and efficacy of intra-arterial treatment in a subgroup analysis of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN). Methods MR CLEAN was a randomised, controlled, open-label, phase 3 trial of intra-arterial treatment in patients (aged ≥18 years from the Netherlands) with proximal arterial occlusion of the anterior circulation, given intra-arterial treatment within 6 h of stroke onset. The primary outcome was 90 day modified Rankin Scale (mRS) score. We estimated the intra-arterial treatment effect for all patients in MR CLEAN who had ASPECTS graded by using multivariable ordinal logistic regression analysis (a proportional odds model) to calculate the adjusted common odds ratio for a shift towards a better functional outcome according to the mRS for intra-arterial treatment and usual care than for usual care alone. We entered an interaction term into the model to test for interaction with prespecified ASPECTS subgroups: 0–4 (large infarct) versus 5–7 (moderate infarct) versus 8–10 (small infarct). MR CLEAN is registered with the Netherlands Trial Registry, number NTR1804, and the ISRCTN Registry, number ISRCTN10888758. Findings 496 patients—232 (47%) in the intra-arterial treatment and usual care group and 264 (53%) in the usual care alone group—were included in the analysis. We noted no significant difference in intra-arterial treatment effect between the ASPECTS subgroups according to 90 day ordinal mRS (adjusted common odds ratio interaction term relative to ASPECTS 8–10: ASPECTS 0–4: 0·79 95% CI 0·20–3·19, p=0·740; and ASPECTS 5–7: 1·02 0·44–2·35, p=0·966). Intra-arterial treatment did not cause a significant increase in the proportion of patients with at least one serious adverse event in any of the ASPECTS subgroups (ASPECTS 0–4: eight 73% of 11 patients in treatment and usual care group vs 11 58% of 19 in usual care alone group, p=0·42; ASPECTS 5–7: 32 59% of 54 vs 19 49% of 39, p=0·31; ASPECTS 8–10: 70 42% of 167 vs 82 40% of 206; p=0·68). For death within 7 days or within 30 days and hemicraniectomy, the differences between the intra-arterial treatment and usual care versus usual care alone groups were not significant by ASPECTS subgroups. A significantly higher proportion of patients had recurrent ischaemic stroke in the intra-arterial treatment plus usual care group than in the usual care alone group in the ASPECTS 8–10 subgroup (eight 5% vs one <1%; p=0·007). Interpretation Contrary to findings from previous studies suggesting that only patients with non-contrast CT ASPECTS of more than 7 benefit from intra-arterial treatment, data from this study suggest that patients with ASPECTS 5–7 should be treated. Further evidence is needed for patients with ASPECTS 0–4, for whom treatment might yield only marginal absolute benefit. Funding Dutch Heart Foundation, AngioCare, Medtronic/Covidien/EV3, Medac/Lamepro, Penumbra, Stryker, and Top Medical.
In patients with ischemic stroke undergoing endovascular treatment (EVT), time to treatment and collateral status are important prognostic factors and may be correlated. We aimed to assess the ...relation between time to CT angiography (CTA) and a quantitatively determined collateral score and to assess whether the collateral score modified the relation between time to recanalization and functional outcome.
We analyzed data from patients with acute ischemic stroke included in the Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke Registry between 2014 and 2017, who had a carotid terminus or M1 occlusion and were treated with EVT within 6.5 hours of symptom onset. A quantitative collateral score (qCS) was determined from baseline CTA using a validated automated image analysis algorithm. We also determined a 4-point visual collateral score (vCS). Multivariable regression models were used to assess the relations between time to imaging and the qCS and between the time to recanalization and functional outcome (90-day modified Rankin Scale score). An interaction term (time to recanalization × qCS) was entered in the latter model to test whether the qCS modifies this relation. Sensitivity analyses were performed using the vCS.
We analyzed 1,813 patients. The median time from symptom onset to CTA was 91 minutes (interquartile range IQR 65-150 minutes), and the median qCS was 49% (IQR 25%-78%). Longer time to CTA was not associated with the log-transformed qCS (adjusted β per 30 minutes, 0.002, 95% CI -0.006 to 0.011). Both a higher qCS (adjusted common odds ratio acOR per 10% increase: 1.06, 95% CI 1.03-1.09) and shorter time to recanalization (acOR per 30 minutes: 1.17, 95% CI 1.13-1.22) were independently associated with a shift toward better functional outcome. The qCS did not modify the relation between time to recanalization and functional outcome (
for interaction: 0.28). Results from sensitivity analyses using the vCS were similar.
In the first 6.5 hours of ischemic stroke caused by carotid terminus or M1 occlusion, the collateral status is unaffected by time to imaging, and the benefit of a shorter time to recanalization is independent of baseline collateral status.
Hemorrhagic transformation (HT) is a complication that may cause neurological deterioration in patients with acute ischemic stroke. Various radiological subtypes of HT can be distinguished. Their ...influence on functional outcome is currently unclear. The purpose of this study was to assess the associations between HT subtypes and functional outcome in acute ischemic stroke patients with proven large vessel occlusion included in the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic stroke in The Netherlands).
All patients with follow-up imaging were included. HT was classified on follow-up CT scans according to the European Cooperative Acute Stroke Study II classification. Functional outcome was assessed using the modified Rankin Scale (mRS) 90 days after stroke onset. Ordinal logistic regression analysis with adjustment for potential confounders was used to determine the association of HT subtypes with functional outcome.
Of 478 patients, 222 had HT. Of these, 76 (16%) patients were classified as hemorrhagic infarction type 1, 71 (15%) as hemorrhagic infarction type 2, 36 (8%) as parenchymal hematoma type 1, and 39 (8%) as parenchymal hematoma type 2. Hemorrhagic infarction type 2 (adjusted common OR (acOR) 0.54, 95% CI: 0.32 to 0.89) and parenchymal hematoma type 2 (acOR 0.37, 95% CI 0.17 to 0.78) were significantly associated with a worse functional outcome. Hemorrhagic infarction type 1 and parenchymal hematoma type 1 were not significantly associated, although their point estimates pointed in the direction of worse outcome.
This study suggests that parenchymal hematoma type 2 is relevant for functional outcome after an acute ischemic stroke, and smaller HTs might also influence long term functional outcome.
ISRCTN10888758.
Recent randomized trials have proven the benefit of intra-arterial treatment (IAT) with retrievable stents in acute ischemic stroke. Patients with poor or absent collaterals (preexistent anastomoses ...to maintain blood flow in case of a primary vessel occlusion) may gain less clinical benefit from IAT. In this post hoc analysis, we aimed to assess whether the effect of IAT was modified by collateral status on baseline computed tomographic angiography in the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN).
MR CLEAN was a multicenter, randomized trial of IAT versus no IAT. Primary outcome was the modified Rankin Scale at 90 days. The primary effect parameter was the adjusted common odds ratio for a shift in direction of a better outcome on the modified Rankin Scale. Collaterals were graded from 0 (absent) to 3 (good). We used multivariable ordinal logistic regression analysis with interaction terms to estimate treatment effect modification by collateral status.
We found a significant modification of treatment effect by collaterals (P=0.038). The strongest benefit (adjusted common odds ratio 3.2 95% confidence intervals 1.7-6.2) was found in patients with good collaterals (grade 3). The adjusted common odds ratio was 1.6 95% confidence intervals 1.0-2.7 for moderate collaterals (grade 2), 1.2 95% confidence intervals 0.7-2.3 for poor collaterals (grade 1), and 1.0 95% confidence intervals 0.1-8.7 for patients with absent collaterals (grade 0).
In MR CLEAN, baseline computed tomographic angiography collateral status modified the treatment effect. The benefit of IAT was greatest in patients with good collaterals on baseline computed tomographic angiography. Treatment benefit appeared less and may be absent in patients with absent or poor collaterals.
URL: http://www.trialregister.nl and http://www.controlled-trials.com. Unique identifier: (NTR)1804 and ISRCTN10888758, respectively.
IMPORTANCE: The positive treatment effect of endovascular therapy (EVT) is assumed to be caused by the preservation of brain tissue. It remains unclear to what extent the treatment-related reduction ...in follow-up infarct volume (FIV) explains the improved functional outcome after EVT in patients with acute ischemic stroke. OBJECTIVE: To study whether FIV mediates the relationship between EVT and functional outcome in patients with acute ischemic stroke. DESIGN, SETTING, AND PARTICIPANTS: Patient data from 7 randomized multicenter trials were pooled. These trials were conducted between December 2010 and April 2015 and included 1764 patients randomly assigned to receive either EVT or standard care (control). Follow-up infarct volume was assessed on computed tomography or magnetic resonance imaging after stroke onset. Mediation analysis was performed to examine the potential causal chain in which FIV may mediate the relationship between EVT and functional outcome. A total of 1690 patients met the inclusion criteria. Twenty-five additional patients were excluded, resulting in a total of 1665 patients, including 821 (49.3%) in the EVT group and 844 (50.7%) in the control group. Data were analyzed from January to June 2017. MAIN OUTCOME AND MEASURE: The 90-day functional outcome via the modified Rankin Scale (mRS). RESULTS: Among 1665 patients, the median (interquartile range IQR) age was 68 (57-76) years, and 781 (46.9%) were female. The median (IQR) time to FIV measurement was 30 (24-237) hours. The median (IQR) FIV was 41 (14-120) mL. Patients in the EVT group had significantly smaller FIVs compared with patients in the control group (median IQR FIV, 33 11-99 vs 51 18-134 mL; P = .007) and lower mRS scores at 90 days (median IQR score, 3 1-4 vs 4 2-5). Follow-up infarct volume was a predictor of functional outcome (adjusted common odds ratio, 0.46; 95% CI, 0.39-0.54; P < .001). Follow-up infarct volume partially mediated the relationship between treatment type with mRS score, as EVT was still significantly associated with functional outcome after adjustment for FIV (adjusted common odds ratio, 2.22; 95% CI, 1.52-3.21; P < .001). Treatment-reduced FIV explained 12% (95% CI, 1-19) of the relationship between EVT and functional outcome. CONCLUSIONS AND RELEVANCE: In this analysis, follow-up infarct volume predicted functional outcome; however, a reduced infarct volume after treatment with EVT only explained 12% of the treatment benefit. Follow-up infarct volume as measured on computed tomography and magnetic resonance imaging is not a valid proxy for estimating treatment effect in phase II and III trials of acute ischemic stroke.
BACKGROUND AND PURPOSE—Ischemic lesion volume (ILV) assessed by follow-up noncontrast computed tomography correlates only moderately with clinical end points, such as the modified Rankin Scale (mRS). ...We hypothesized that the association between follow-up noncontrast computed tomography ILV and outcome as assessed with mRS 3 months after stroke is strengthened when taking the mRS relevance of the infarct location into account.
METHODS—An anatomic atlas with 66 areas was registered to the follow-up noncontrast computed tomographic images of 254 patients from the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands). The anatomic brain areas were divided into brain areas of high, moderate, and low mRS relevance as reported in the literature. Based on this distinction, the ILV in brain areas of high, moderate, and low mRS relevance was assessed for each patient. Binary and ordinal logistic regression analyses with and without adjustment for known confounders were performed to assess the association between the ILVs of different mRS relevance and outcome.
RESULTS—The odds for a worse outcome (higher mRS) were markedly higher given an increase of ILV in brain areas of high mRS relevance (odds ratio, 1.42; 95% confidence interval, 1.31–1.55 per 10 mL) compared with an increase in total ILV (odds ratios, 1.16; 95% confidence interval, 1.12–1.19 per 10 mL). Regression models using ILV in brain areas of high mRS relevance instead of total ILV showed a higher quality.
CONCLUSIONS—The association between follow-up noncontrast computed tomography ILV and outcome as assessed with mRS 3 months after stroke is strengthened by accounting for the mRS relevance of the affected brain areas. Future prediction models should account for the ILV in brain areas of high mRS relevance.
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