A pragmatic approach using magnetic resonance imaging to treat ischemic strokes of unknown onset time in a thrombolytic trial

Abstract

Background and purpose: Toward the goal of designing a clinical trial using imaging parameters to treat stroke patients with unknown onset time, we investigated the timing of changes on MRI in patients with well-defined stroke onset.

Methods: Hypothesis-generating (n=85) and confirmatory (n=111) samples were scored by blinded readers for fluid-attenuated inversion recovery (FLAIR) hyperintensity in diffusion-positive regions. Reader-measured signal intensity ratio (SIR) of the lesion to contralateral tissue was compared with SIR measured by coregistration.

Results: Lesion conspicuity increased with time on FLAIR (P=0.006). Qualitative assessment of FLAIR-negative vs FLAIR hyperintensity (k=0.7091; 95% CI, 0.61-0.81) showed good interrater agreement. Subtle hyperintensity was less reliably categorized (k=0.59; 95% CI, 0.47-0.71). Reader-measured SIR <1.15 can identify patients within the treatable time window of 4.5 hours (positive predictive value=0.90). The SIR was greater for right hemisphere lesions (P=0.04) for a given reported time from stroke symptom onset.

Conclusions: The SIR on FLAIR provides a quantitative tool to identify early ischemic strokes. In developing SIR thresholds, right hemisphere lesions may confound the accurate estimate of stroke onset time. Image coregistration for thrombolytic trial enrollment is not necessary. A SIR <1.15 on FLAIR yields a practical estimate of stroke onset within 4.5 hours.

Figure 1

Example images from three different patients representative of each of the three qualitative ratings of none, subtle, and bright FLAIR hyperintensity.

Figure 2

The sensitivity and specificity for binary classification based on signal intensity ratio (SIR) as a function of threshold for the time-window of 0–4.5 hours. The arrow indicates the optimum SIR threshold where sensitivity and specificity are approximately equal.