Ischemic Core and Hypoperfusion Volumes Correlate With Infarct Size 24 Hours After Randomization in DEFUSE 3

Abstract

Background and Purpose— Accurate prediction of the subsequent infarct volume early after stroke onset helps determine appropriate interventions and prognosis. In the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke), we evaluated the accuracy of baseline ischemic core and hypoperfusion volumes for predicting infarct volume 24 hours after randomization to endovascular thrombectomy versus medical management. We also assessed if the union of baseline ischemic core and the volume of persistent hypoperfusion at 24 hours after randomization predicts infarct volume. Methods— Patients in DEFUSE 3 with computed tomography perfusion imaging or magnetic resonance diffusion weighted imaging/perfusion imaging acquired at baseline and at 24 hours after randomization were included. Ischemic core and Tmax >6s hypoperfusion volumes at baseline and follow-up were calculated using RAPID software and compared with the infarct volumes obtained 24 hours after randomization. Patients were stratified by reperfusion status for analyses. Results— Of 125 eligible patients, 59 patients with >90% reperfusion had a strong correlation between baseline ischemic core volume and infarct volume 24 hours postrandomization ( r =0.83; P <0.0001), and 14 patients with <10% reperfusion had a strong correlation between baseline Tmax >6s volume and infarct volume 24 hours postrandomization ( r =0.77; P <0.001). In the 52 patients with 10% to 90% reperfusion, as well as in all 125 patients, the union of the baseline ischemic core and the follow-up Tmax >6s perfusion volume was highly correlated with infarct volume 24 hours postrandomization (for N=125; r =0.83; P <0.0001), with a median absolute difference of 21.3 mL between observed and predicted infarct volumes. Conclusions— The union of the irreversibly injured ischemic core and persistently hypoperfused tissue volumes, as identified by computed tomography perfusion or magnetic resonance diffusion weighted imaging/perfusion, predicted infarct volume at 24 hours after randomization in DEFUSE 3 patients. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

Computed Tomography Perfusion Core Infarct Measurement Compared to Diffusion-Weighted Magnetic Resonance Imaging in Patients with Revascularization of Anterior Circulation, Large Artery Occlusion Ischemic Stroke

“…The time delay between initial CTP imaging and revascularization may have led to infarct growth, although mean time between CTP and revascularization in our study was 1.9 h, comparable to other studies [11,14]. In addition, more delayed MRI imaging might have produced larger infarct sizes, given the potential for infarct growth with increased time from stroke onset [13].…”

“…Previously, Albers et al [8] demonstrated accurate infarct volume estimates with CTP in subjects enrolled in SWIFT-PRIME. More recently, in a cohort of 59 patients enrolled in DEFUSE 3 who achieved > 90% revascularization, baseline core infarct volumes showed a strong correlation with 24-h infarct volumes [11]. Our results may be explained by infarct growth after CTP.…”

“…Median infarct volumetric difference was 9 cc in our study, compared to 13 cc [8], 21.3 cc [11], and 25.4 cc [14] per other groups who utilized the same CBF and DWI threshold parameters. Hoving et al found that infarct overestimation was uncommon [14].…”

“…Prior studies have demonstrated that reduced relative CBF of less than 30% accurately estimates final infarct volume on diffusion-weighted imaging magnetic resonance imaging (DWI MRI) [8], while others have shown ischemic core overestimation with the same parameter, illustrating the so-called "ghost core infarct" concept [9,10]. A more recent trial utilized prospectively collected data from the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) and the Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK) trials to retrospectively determine DWI and CTP CBF < 30% differences in patients who achieved early, good revascularization of a LAO [11]. CTP core overestimation was rare, and median core underestimation exceeded 25 cm 3 (cc).…”

Collateral status contributes to differences between observed and predicted 24-h infarct volumes in DEFUSE 3

“…We previously demonstrated that imaging measures obtained from CT or MR scans obtained at baseline correlated with the size of the infarct 24 h after randomization in DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). 1 In particular, the infarct volume 24 h after randomization was predicted by the size of the estimated ischemic core in patients who achieved >90% reperfusion. Furthermore, the volume of critically hypoperfused tissue at baseline, as measured by a time to maximum of the residue function of more than 6 seconds (Tmax > 6 s), predicted infarct volume at 24 h in patients who achieved <10% reperfusion.…”