Prevalence of Imaging Biomarkers to Guide the Planning of Acute Stroke Reperfusion Trials.

BACKGROUND AND PURPOSE: Imaging biomarkers are increasingly used as selection criteria for stroke clinical trials. The goal of our study was to determine the prevalence of commonly studied imaging biomarkers in different time windows after acute ischemic stroke onset to better facilitate the design of stroke clinical trials using such biomarkers for patient selection. METHODS: This retrospective study included 612 patients admitted with a clinical suspicion of acute ischemic stroke with symptom onset no more than 24 hours before completing baseline imaging. Patients with subacute/chronic/remote infarcts and hemorrhage were excluded from this study. Imaging biomarkers were extracted from baseline imaging, which included a noncontrast head computed tomography (CT), perfusion CT, and CT angiography. The prevalence of dichotomized versions of each of the imaging biomarkers in several time windows (time since symptom onset) was assessed and statistically modeled to assess time dependence (not lack thereof). RESULTS: We created tables showing the prevalence of the imaging biomarkers pertaining to the core, the penumbra and the arterial occlusion for different time windows. All continuous imaging features vary over time. The dichotomized imaging features that vary significantly over time include: noncontrast head computed tomography Alberta Stroke Program Early CT (ASPECT) score and dense artery sign, perfusion CT infarct volume, and CT angiography collateral score and visible clot. The dichotomized imaging features that did not vary significantly over time include the thresholded perfusion CT penumbra volumes. CONCLUSIONS: As part of the feasibility analysis in stroke clinical trials, this analysis and the resulting tables can help investigators determine sample size and the number needed to screen.

Factors influencing infarct growth including collateral status assessed using computed tomography in acute stroke patients with large artery occlusion.

In major ischemic stroke caused by a large artery occlusion, neuronal loss varies considerably across individuals without revascularization. This study aims to identify which patient characteristics are most highly associated with this variability. Demographic and clinical information were retrospectively collected on a registry of 878 patients. Imaging biomarkers including Alberta Stroke Program Early CT score, noncontrast head computed tomography infarct volume, perfusion computed tomography infarct core and penumbra, occlusion site, collateral score, and recanalization status were evaluated on the baseline and early follow-up computed tomography images. Infarct growth rates were calculated by dividing infarct volumes by the time elapsed between the computed tomography scan and the symptom onset. Collateral score was graded into four levels (0, 1, 2, and 3) in comparison with the normal side. Correlation of perfusion computed tomography and noncontrast head computed tomography infarct volumes and infarct growth rates were estimated with the nonparametric Spearman's rank correlation. Conditional inference trees were used to identify the clinical and imaging biomarkers that were most highly associated with the infarct growth rate and modified Rankin Scale at 90 days. Two hundred and thirty-two patients met the inclusion criteria for this study. The median infarct growth rates for perfusion computed tomography and noncontrast head computed tomography were 11.2 and 6.2 ml/log(min) in logarithmic model, and 18.9 and 10.4 ml/h in linear model, respectively. Noncontrast head computed tomography and perfusion computed tomography infarct volumes and infarct growth rates were significantly correlated (rho=0.53; P < 0.001). Collateral status was the strongest predictor for infarct growth rates. For collateral=0, the perfusion computed tomography and noncontrast head computed tomography infarct growth rate were 31.56 and 16.86 ml/log(min), respectively. Patients who had collateral >0 and penumbra volumes>92 ml had the lowest predicted perfusion computed tomography infarct growth rates (6.61 ml/log(min)). Collateral status was closely related to the diversity of infarct growth rates, poor collaterals were associated with a faster infarct growth rates and vice versa.