- Title
- Assessing response to stroke thrombolysis validation of 24-hour multimodal magnetic resonance imaging
- Creator
- Campbell, Bruce C. V.; Tu, Hans T. H.; Davis, Stephen M.; Østergaard, Leif; Parsons, Mark W.; Christensen, Søren; Desmond, Patricia M.; Levi, Christopher R.; Bladin, Christopher F.; Hjort, Niels; Ashkanian, Mahmoud; Sølling, Christine; Donnan, Geoffrey A.
- Relation
- Archives of Neurology Vol. 69, Issue 1, p. 46-50
- Publisher Link
- http://dx.doi.org/10.1001/archneurol.2011.232
- Publisher
- American Medical Association
- Resource Type
- journal article
- Date
- 2012
- Description
- Background: Imaging is used as a surrogate for clinical outcome in early-phase stroke trials. Assessment of infarct growth earlier than the standard 90 days used for clinical end points may be equally accurate and more practical. Objective: To compare assessment of the effect of reperfusion therapies using 24-hour vs day 90 magnetic resonance imaging. Design: Infarct volume was assessed on diffusion-weighted imaging (DWI) at baseline and 24 hours after stroke onset and on fluid-attenuated inversion recovery images at day 90. The DWI and fluid-attenuated inversion recovery lesions were manually outlined by 2 independent raters, and the volumes were averaged. Interrater consistency was assessed using the median difference in lesion volume between raters. Setting: Referral center. Patients: Imaging data were available for 83 patients; 77 of these patients received thrombolysis. Main Outcome Measures: Infarct volume at 24 hours and 90 days. Results: The 24-hour DWI infarct volume had a strong linear correlation with day 90 fluid-attenuated inversion recovery infarct volume (r = 0.98, 95% confidence interval, 0.97-0.99). Recanalization had a significant effect on infarct evolution between baseline and 24 hours but not between 24 hours and day 90. Infarct growth from baseline was significantly reduced by recanalization, whether assessed at 24 hours or day 90. Infarct volume at either time point predicted functional outcome independent of age and baseline stroke severity. Interrater agreement was better for DWI than fluid-attenuated inversion recovery (1.4 mL [8%] vs 1.8 mL [17%]; P = .002). Conclusions: Assessment of final infarct volume using DWI at 24 hours captures the effect of reperfusion therapies on infarct growth and predicts functional outcome similarly to imaging at day 90. This has the potential to reduce loss to follow-up in trials and may add early prognostic information in clinical practice. Infarct growth can be used as a surrogate marker for clinical outcome in ischemic stroke trials. This provides a meaningful intermediary between preclinical studies, where drug effects are often assessed on the basis of infarct volume attenuation, and phase 3 clinical outcomes. In the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) study and the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET), recanalization and reperfusion have been demonstrated to significantly reduce infarct growth. Although thrombolysis did not significantly attenuate infarct growth in the primary EPITHET analysis, subsequent analysis using more stringent optimized perfusion thresholds developed in positron emission tomography and magnetic resonance imaging has demonstrated reduced growth in patients who received thrombolysis. Traditionally, stroke trial clinical end points are assessed at 90 days following stroke. There has been less consensus around the timing of imaging outcome assessments. However, these have generally been delayed, eg, 30 days in the DEFUSE study and 90 days in EPITHET. However, these were arbitrary choices and have some distinct disadvantages. By days 30 to 90, significant atrophy of the infarcted region has taken place. This leads to an underestimate of the infarct volume relative to the baseline brain topography. There is also a real risk of loss to imaging follow-up given the requirement for in-person attendance at 1 to 3 months when the patient may be at home or in a nursing institution with limited access to transportation. Some loss to follow-up also occurs due to early mortality. In the DEFUSE study and EPITHET, 25% of patients were unable to participate in day 30 or day 90 imaging, respectively (16% died and 9% were unavailable). Assessment of final infarct volume at earlier time points may therefore be more accurate and yield major practical advantages.11 Magnetic resonance diffusion-weighted imaging (DWI) has recently been confirmed as a reliable indicator of irreversible infarction.10A 24-hour scan is commonly obtained in routine clinical practice to assess for hemorrhagic transformation after thrombolysis. We therefore examined the potential for 24-hour DWI to predict day 90 fluid-attenuated inversion recovery (FLAIR) lesion volumes and clinical outcome data. We also assessed the interrater variability in manually outlined lesion volumes using the 2 modalities.
- Subject
- response; stroke thrombolysis; magnetic resonance imaging; stroke trials; clinical outcomes
- Identifier
- http://hdl.handle.net/1959.13/1311459
- Identifier
- uon:22216
- Identifier
- ISSN:0003-9942
- Language
- eng
- Full Text
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