Can Imaging Determine the Window of Eligibility for Reperfusion Therapy in Stroke?

LOS ANGELES—Can brain imaging supplant clocks for identifying patients with acute ischemic stroke who will benefit from thrombolytic treatment or thrombectomy?

That scenario is what experts envision, based on early findings from several studies. Although the evidence is not yet definitive enough to justify using imaging as a replacement for time from stroke onset in routine practice, the results so far are encouraging and have led to the start or planning of several phase III trials that will try to determine a role for imaging, either CT or MR, to identify patients who qualify for reperfusion therapy.

“What we’re trying to do is move away from using the clock as a surrogate marker and instead use imaging as the surrogate,” said Jenny P. Tsai, MDCM, Neuroimaging and Vascular Neurology Fellow at the Stanford Stroke Center in California.

Jenny P. Tsai, MDCM

Time from the onset of stroke symptoms to initiation of thrombolytic or endovascular treatment makes no allowance for patient-to-patient variations in collateral cerebral circulation, a factor that appears to make a big difference in whether patients can be many more hours removed from the start of their stroke and still save threatened brain tissue. In addition, relying on time since stroke symptom onset can lead to a flawed estimate of a stroke’s duration when patients have an unwitnessed stroke.

The alternative is to use either CT perfusion imaging or a combination of MR perfusion and diffusion-weighted imaging “to get effective reperfusion treatments to patients who present at later time windows,” said Gregory W. Albers, MD, Professor of Neurology at Stanford University and Director of the Stanford Stroke Center. He called these two new approaches to gauging a patient’s suitability for reperfusion therapy “the next big thing in imaging” for stroke.

Using CT Perfusion to Assess Target Mismatch

Dr. Tsai presented an analysis of thrombectomy reperfusion in patients enrolled in the CT Perfusion to Predict Response to Recanalization in Ischemic Stroke Project (CRISP), which included 201 patients with acute ischemic stroke and large cerebral-artery occlusions who were treated at six US centers. The analysis excluded nine patients who presented more than 18 hours after their stroke onset, six patients who did not have successful CT perfusion assessment, and five additional patients excluded for other reasons. The 181 patients analyzed included 125 with a target mismatch in CT perfusion, indicating that salvageable tissue remained in the area of their stroke. Among these 125 patients, 111 underwent successful reperfusion by thrombectomy.

The researchers identified good treatment outcomes as a modified Rankin Scale score of 2 or less at 90 days after treatment. A multivariate analysis showed that among these 111 patients, achievement of a good 90-day outcome had no statistically significant relationship with time-to-treatment out to at least the first eight hours following stroke onset, reported Dr. Tsai. The data also showed a nonsignificant relationship between good outcomes and time from stroke onset to treatment beyond eight hours, but the confidence interval for this relationship widened at later times as the analysis focused on fewer and fewer patients.

“In patients with large-artery occlusions who have a target mismatch profile [on perfusion CT] and achieve successful reperfusion, there is no significant association between onset to reperfusion time and the probability of a good functional outcome,” suggesting that “CT perfusion is a biomarker of good outcomes beyond six hours” after stroke onset, Dr. Tsai concluded. CT perfusion has the advantage of being more widely available than MRI is, she added. Last year, her associates at Stanford reported similar findings using perfusion–diffusion mismatch in the cerebral area around a stroke visualized with MRI.

The findings reported by Dr. Tsai require confirmation in the several prospective, randomized trials that are under way, Dr. Albers said.

Using MRI in Unwitnessed Strokes

Unwitnessed strokes, with an unknown elapsed time from onset to presentation, pose another challenge. Investigators evaluated the ability of MRI to help identify patients with unwitnessed stroke who can safely receive IV thrombolytic therapy with alteplase in the MR WITNESS (Study of Intravenous Thrombolysis With Alteplase in MRI-Selected Patients) trial.

The study enrolled 80 patients with an unwitnessed acute ischemic stroke at 10 US centers. Patients needed to be able to receive alteplase within four and a half hours of when their stroke was first identified; 57 (71%) of the participants had wake-up strokes. All patients underwent two types of MRI to identify them as potential candidates for safe administration of alteplase: diffusion-weighted imaging to identify that a stroke had occurred, and fluid-attenuated inversion recovery (FLAIR) assessment to identify strokes that had occurred during the prior four hours.