Intravenous alteplase is the only approved treatment for acute ischemic stroke. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, is an alternative thrombolytic agent. In this phase 2B trial, we randomly assigned 75 patients to receive alteplase (0.9 mg per kilogram of body weight) or tenecteplase (0.1 mg per kilogram or 0.25 mg per kilogram) less than 6 hours after the onset of ischemic stroke. To favor the selection of patients most likely to benefit from thrombolytic therapy, the eligibility criteria were a perfusion lesion at least 20% greater than the infarct core on computed tomographic (CT) perfusion imaging at baseline and an associated vessel occlusion on CT angiography. The coprimary end points were the proportion of the perfusion lesion that was reperfused at 24 hours on perfusion-weighted magnetic resonance imaging and the extent of clinical improvement at 24 hours as assessed on the National Institutes of Health Stroke Scale (NIHSS, a 42-point scale on which higher scores indicate more severe neurologic deficits). The three treatment groups each comprised 25 patients. The mean (±SD) NIHSS score at baseline for all patients was 14.4±2.6, and the time to treatment was 2.9±0.8 hours. Together, the two tenecteplase groups had greater reperfusion (P=0.004) and clinical improvement (P<0.001) at 24 hours than the alteplase group. There were no significant between-group differences in intracranial bleeding or other serious adverse events. The higher dose of tenecteplase (0.25 mg per kilogram) was superior to the lower dose and to alteplase for all efficacy outcomes, including absence of serious disability at 90 days (in 72% of patients, vs. 40% with alteplase; P=0.02). Tenecteplase was associated with significantly better reperfusion and clinical outcomes than alteplase in patients with stroke who were selected on the basis of CT perfusion imaging. (Funded by the Australian National Health and Medical Research Council; Australia New Zealand Clinical Trials Registry number, ACTRN12608000466347.)

It is unknown whether collateral vessel status, as seen on computed tomography angiography, can predict the fate of penumbral tissue identified on perfusion computed tomography and thereby influence clinical outcome. We tested this hypothesis in consecutive patients who underwent perfusion computed tomography/computed tomography angiography within 6 h of anterior circulation stroke, who also had repeat perfusion/infarct volume imaging at 24 h, and modified Rankin Scale at 3 months. Collateral status was graded as good or reduced depending on the extent of contrast visualized distal to the occlusion on computed tomography angiography. ‘Perfusion computed tomography mismatch’ ratio was calculated from the ratio of the mean transit time lesion/cerebral blood volume lesion. Of 92 patients with proximal intracranial vessel occlusion, good collateral status (51/92) was significantly associated with reduced infarct expansion and more favourable functional outcomes (modified Rankin Scale 0–2). Significant univariate predictors of favourable outcome were good collateral status, major reperfusion at 24 h, presence of perfusion computed tomography mismatch (for a range of ratios: ≥1.2, ≥2, ≥3, ≥3.5) and baseline National Institutes of Health Stroke Scale score. Notably, none of the 37 patients with a perfusion computed tomography mismatch ratio < 3.0 had a favourable outcome. In patients with perfusion computed tomography mismatch, significant independent predictors of favourable outcome were good collateral status, major reperfusion and baseline National Institutes of Health Stroke Scale score. There was also a strong interaction between major reperfusion and good collateral status in the regression models. In patients with proximal vessel occlusion, perfusion computed tomography mismatch is a prerequisite for a favourable clinical response, but good collateral status appears a critical determinant of ultimate outcome, particularly if major reperfusion occurs.

To perform a large-scale systematic comparison of the accuracy of all commonly used perfusion computed tomography (CT) data postprocessing methods in the definition of infarct core and penumbra in acute stroke. The collection of data for this study was approved by the institutional ethics committee, and all patients gave informed consent. Three hundred fourteen patients with hemispheric ischemia underwent perfusion CT within 6 hours of stroke symptom onset and magnetic resonance (MR) imaging at 24 hours. CT perfusion maps were generated by using six different postprocessing methods. Pixel-based analysis was used to calculate sensitivity and specificity of different perfusion CT thresholds for the penumbra and infarct core with each postprocessing method, and receiver operator characteristic (ROC) curves were plotted. Area under the ROC curve (AUC) analysis was used to define the optimum threshold. Delay-corrected singular value deconvolution (SVD) with a delay time of more than 2 seconds most accurately defined the penumbra (AUC = 0.86, P = .046, mean volume difference between acute perfusion CT and 24-hour diffusion-weighted MR imaging = 1.7 mL). A double core threshold with a delay time of more than 2 seconds and cerebral blood flow less than 40% provided the most accurate definition of the infarct core (AUC = 0.86, P = .038). The other SVD measures (block circulant, nondelay corrected) were more accurate than non-SVD methods. This study has shown that there is marked variability in penumbra and infarct prediction among various deconvolution techniques and highlights the need for standardization of perfusion CT in stroke. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120971/-/DC1.