Validation of automated Alberta Stroke Program Early CT Score (ASPECTS) software for detection of early ischemic changes on non-contrast brain CT scans

Purpose: In ASPECTS, 10 brain regions are scored visually for presence of acute ischemic stroke damage. We evaluated automated ASPECTS in comparison to expert readers. Methods: Consecutive, baseline non-contrast CT-scans (5-mm slice thickness) from the prospective MR CLEAN trial (n = 459, MR CLEAN Netherlands Trial Registry number: NTR1804) were evaluated. A two-observer consensus for ASPECTS regions (normal/abnormal) was used as reference standard for training and testing (0.2/0.8 division). Two other observers provided individual ASPECTS-region scores. The Automated ASPECTS software was applied. A region score specificity of ≥ 90% was used to determine the software threshold for detection of an affected region based on relative density difference between affected and contralateral region. Sensitivity, specificity, and receiver-operating characteristic curves were calculated. Additionally, we assessed intraclass correlation coefficients (ICCs) for automated ASPECTS and observers in comparison to the reference standard in the test set. Results: In the training set (n = 104), with software thresholds for a specificity of ≥ 90%, we found a sensitivity of 33–49% and an area under the curve (AUC) of 0.741–0.785 for detection of an affected ASPECTS region. In the test set (n = 355), the results for the found software thresholds were 89–89% (specificity), 41–57% (sensitivity), and 0.750–0.795 (AUC). Comparison of automated ASPECTS with the reference standard resulted in an ICC of 0.526. Comparison of observers with the reference standard resulted in an ICC of 0.383–0.464. Conclusion: The performance of automated ASPECTS is comparable to expert readers and could support readers in the detection of early ischemic changes

Value of thrombus CT Characteristics in Patients with Acute Ischemic Stroke

BACKGROUND AND PURPOSE: Thrombus CT characteristics might be useful for patient selection for intra-arterial treatment. Our objective was to study the association of thrombus CT characteristics with outcome and treatment effect in patients with acute ischemic stroke. MATERIALS AND METHODS: We included 199 patients for whom thin-section NCCT and CTA within 30 minutes from each other were available in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute ischemic stroke in the Netherlands (MR CLEAN) study. We assessed the following thrombus characteristics: location, distance from ICA terminus to thrombus, length, volume, absolute and relative density

qTICI: Quantitative assessment of brain tissue reperfusion on digital subtraction angiograms of acute ischemic stroke patients

Background: The Thrombolysis in Cerebral Infarction (TICI) scale is an important outcome measure to evaluate the quality of endovascular stroke therapy. The TICI scale is ordinal and observer-dependent, which may result in suboptimal prediction of patient outcome and inconsistent reperfusion grading. Aims: We present a semi-automated quantitative reperfusion measure (quantified TICI (qTICI)) using image processing techniques based on the TICI methodology. Methods: We included patients with an intracranial proximal large vessel occlusion with complete, good quality runs of anteroposterior and lateral digital subtraction angiography from the MR CLEAN Registry. For each vessel occlusion, we identified the target downstream territory and automatically segmented the reperfused area in the target downstream territory on final digital subtraction angiography. qTICI was defined as the percentage of reperfused area in target downstream territory. The value of qTICI and extended TICI (eTICI) in predicting favorable functional outcome (modified Rankin Scale 0–2) was compared using area under receiver operating characteristics curve and binary logistic regression analysis unadjusted and adjusted for known prognostic factors. Results: In total, 408 patients with M1 or internal carotid artery occlusion were included. The median qTICI was 78 (interquartile range 58–88) and 215 patients (53%) had an eTICI of 2C or higher. qTICI was comparable to eTICI in predicting favorable outcome with area under receiver operating characteristics curve of 0.63 vs. 0.62 (P = 0.8) and 0.87 vs. 0.86 (P = 0.87), for the unadjusted and adjusted analysis, respectively. In the adjusted regression analyses, both qTICI and eTICI were independently associated with functional outcome. Conclusion: qTICI provides a quantitative measure of reperfusion with similar prognostic value for functional outcome to eTICI score

National Institutes of Health Stroke Scale: An Alternative Primary Outcome Measure for Trials of Acute Treatment for Ischemic Stroke

Background and Purpose- The modified Rankin Scale (mRS) at 3 months is the most commonly used primary outcome measure in stroke treatment trials, but it lacks specificity and requires long-term follow-up interviews, which consume time and resources. An alternative may be the National Institutes of Health Stroke Scale (NIHSS), early after stroke. Our aim was to evaluate whether the NIHSS assessed within 1 week after treatment could serve as a primary outcome measure for trials of acute treatment for ischemic stroke. Methods- We used data from 2 randomized controlled trials of endovascular treatment for ischemic stroke: the positive MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; N=500) and the neutral IMS (Interventional Management of Stroke) III trial (N=656). We used a causal mediation model, with linear and ordinal logistic regression adjusted for confounders, to evaluate the NIHSS 24 hours and 5 to 7 days after endovascular treatment as primary outcome measures (instead of the mRS at 3 months) in both trials. Patients who had died before the NIHSS was assessed received the maximum score of 42. NIHSS+1 was then log10-transformed. Results- In both trials, there was a significant correlation between the NIHSS at 24 hours and 5 to 7 days and the mRS. In MR CLEAN, we found a significant effect of endovascular treatment on the mRS and on the NIHSS at 24 hours and 5 to 7 days. After adjustment for NIHSS at 24 hours and 5 to 7 days, the effect of endovascular treatment on the mRS decreased from common odds ratio 1.68 (95% CI, 1.22-2.32) to respectively 1.36 (95% CI, 0.97-1.91) and 1.24 (95% CI, 0.87-1.79), indicating that treatment effect on the mRS is in large part mediated by the NIHSS. In the IMS III trial there was no treatment effect on the NIHSS at 24 hours and 5 to 7 days, corresponding with the absence of a treatment effect on the mRS. Conclusions- The NIHSS within 1 week satisfies the requirements for a surrogate end point and may be used as a primary outcome measure in trials of acute treatment for ischemic stroke, particularly in phase II(b) trials. This could reduce stroke-outcome assessment to its essentials (ie, neurological deficit), and reduce trial duration and costs. Whether and under which conditions it could be used in phase III trials requires a debate in the field with all parties. Clinical Trial Registration- URL: http://www.isrctn.com. Unique identifier: ISRCTN10888758; https://www.clinicaltrials.gov. Unique identifier: NCT00359424

A decrease in blood pressure is associated with unfavorable outcome in patients undergoing thrombectomy under general anesthesia

Background Up to two-thirds of patients are either dependent or dead 3 €months after thrombectomy for acute ischemic stroke (AIS). Loss of cerebral autoregulation may render patients with AIS vulnerable to decreases in mean arterial pressure (MAP). Objective To determine whether a fall in MAP during intervention under general anesthesia (GA) affects func

Automatic segmentation of cerebral infarcts in follow-up computed tomography images with convolutional neural networks

Background and purpose: Infarct volume is a valuable outcome measure in treatment trials of acute ischemic stroke and is strongly associated with functional outcome. Its manual volumetric assessment is, however, too demanding to be implemented in clinical practice. Objective: To assess the value of convolutional neural networks (CNNs) in the automatic segmentation of infarct volume in follow-up CT images in a large population of patients with acute ischemic stroke. Materials and methods: We included CT images of 1026 patients from a large pooling of patients with acute ischemic stroke. A reference standard for the infarct segmentation was generated by manual delineation. We introduce three CNN models for the segmentati

Eine Einführung in die Inverted-Classroom-Methode in der medizinischen Ausbildung

Zielgruppe: Der Workshop richtet sich an alle Personen, die sich für die Inverted Classroom Methode(ICM) interessieren und diese ggf. für eigene Lehrprojekte anwenden möchten Lernziele: Ziel des Workshops ist es, die Teilnehmer zu befähigen, die ICM auf die eigene Lehre anzuwenden. Inhalt: Der Workshop gibt eine Einführung in die ICM, skizziert ihre Vor- und Nachteile unter Einbeziehung aktueller Forschungsergebnisse und vermittelt praktische Fertigkeiten, um eigene Konzept für die Lehre entwickeln zu können. Dabei werden zusätzlich Themen wie Video-und Screencasterstellung, Open Educational Resources und Urheberrechte skizziert. Ablauf: Der Workshop selbst ist nach der ICM konzipiert. Das bedeutet, dass sich die Teilnehmer bereits im Vorfeld in einer Online-Phase das notwendige Faktenwissen aneignen, um in der Präsenzphase das erlernte Wissen in Kleingruppen anzuwenden und ICM-Konzepte für die eigene Lehre zu entwickeln. Diese Konzepte werden am Ende in der Gruppe vorgestellt und diskutier

Automated entire thrombus density measurements for robust and comprehensive thrombus characterization in patients with acute ischemic stroke

Background and Purpose: In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success. However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition. Our aim was first to introduce an automated method to assess the entire thrombus density and then to compare the measured entire thrombus density with respect to current standard manual measurements. Materials and Method: In 135 AIS patients, the density distribution of the entire thrombus was determined. Density distributions were described usingmedians, interquartile ranges (IQR), kurtosis, and skewedness. Differences between themedian of entire thrombusmeasurements and commonly applied manualmeasurements using 3 regions of interest were determined using linear regression. Results: Density distributions varied considerably with medians ranging from 20.0 to 62.8 HU and IQRs ranging from 9.3 to 55.8 HU. The average median of the thrombus density distributions (43.5 ± 10.2 HU) was lower than the manual assessment (49.6 ± 8.0 HU) (p<0.05). The difference between manual measurements and median density of entire thrombus decreased with increasing density (r = 0.64; p<0.05), revealing relatively higher manual measurements for low density thrombi such that manual density measurement tend overestimates the real thrombus density. Conclusions: Automatic measurements of the full thrombus expose a wide variety of thrombi density distribution, which is not grasped with currently used manual measurement. Furthermore, d

Two-year clinical follow-up of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN): Design and statistical analysis plan of the extended follow-up study

Background: MR CLEAN was the first randomized trial to demonstrate the short-term clinical effectiveness of endovascular treatment in patients with acute ischemic stroke caused by large vessel occlusion in the anterior circulation. Several other trials confirmed that endovascular treatment improves clinical outcome at three months. However, limited data are available on long-term clinical outcome. We aimed to estimate the effect of endovascular treatment on functional outcome at two-year follow-up in patients with acute ischemic stroke. Secondly, we aimed to assess the effect of endovascular treatment on major vascular events and mortality during two years of follow-up. Methods: MR CLEAN is a multicenter clinical trial with randomized treatment allocation, open-label treatment, and blinded endpoint evaluation. Patients included were 18 years or older with acute ischemic stroke caused by a proven anterior proximal artery occlusion who could be treated within six hours after stroke onset. The intervention contrast was endovascular treatment and usual care versus no endovascular treatment and usual care. The current study extended the follow-up duration from three months to two years. The primary outcome is the score on the modified Rankin scale at two years. Secondary outcomes include all-cause mortality and the occurrence of major vascular events within two years of follow-up. Discussion: The results of our study provide information on the long-term clinical effectiveness of endovascular treatment, which may have implications for individual treatment decisions and estimates of cost-effectiveness. Trial registration:NTR1804. Registered on 7 May 2009; ISRCTN10888758. Registered on 24 July 2012 (main MR CLEAN trial); NTR5073. Registered on 26 February 2015 (extended follow-up study)