Probability of Cortical Infarction Predicted by Flumazenil Binding and Diffusion-Weighted Imaging Signal Intensity

Abstract

Background and Purpose— The differentiation of reversible from irreversible ischemic damage is essential for identifying patients with acute ischemic deficits who may benefit from therapeutic interventions. Diffusion-weighted imaging (DWI) has become the method of choice to detect ischemic lesions. Positron emission tomography (PET) of the central benzodiazepine receptor ligand 11C flumazenil (FMZ) has been shown to be a reliable marker of neuronal integrity. These 2 imaging parameters were compared with respect to the probability to predict cortical infarction in early ischemic stroke. Methods— In 12 patients with acute stroke, results from DWI (median, 6.5 hours after symptom onset) and FMZ–PET (interval, 85 minutes between DWI and PET) were compared with infarct extension 24 to 48 hours after onset of stroke on T2-weighted magnetic resonance imaging (T2-MRI). Probability curves predictive of eventual infarction were computed using respective DWI, FMZ, and apparent diffusion coefficient (ADC) values for voxels of interest (VOI) later classified as representing infarcted or noninfarcted tissue. Results— Ninety-five percent limits predictive of cortical infarction were determined for relative FMZ binding (≤3.2), DWI signal intensity (≥1.18), and ADC values (≤0.83). Cortical regions with values beyond these 95% limits did not necessarily overlap with nor were fully congruous with final cortical infarct volumes. The respective median volumes for these regions were FMZ median 10.9, range 0 to 99.7 cm 3 ; DWI median 15.2, range 0 to 116.0 cm 3 ; ADC median 12.4, range 0 to 112.7 cm 3 ; and final infarct median 14.9, range 0 to 114.7 cm 3 . Overall, 83.5% of the final infarct, on average, was predicted by decreased FMZ binding, 84.7% by increased DWI signal intensity, and 70.9% by a decreased ADC value. The portions of the final infarct not predicted in the early investigation (false-negatives) were 4.8 cm 3 (median) for FMZ, 3.7 cm 3 for DWI, and 6.0 cm 3 for ADC. The false-positive volumes not included in the final infarct were 0 cm 3 (median) for FMZ, 5.1 cm 3 for DWI, and 3.6 cm 3 for ADC. Conclusions— These results indicate that FMZ–PET and DWI are comparable in the prediction of probability of ischemic cortical infarction, but FMZ–PET carries a lower probability of false-positive prediction. The final infarcts include tissue not identified by these imaging modalities; at the time of the study, these tissue compartments are viable and could benefit from treatment. The discrepancy in predictive probability could be related to the fundamental difference of the measured variables: benzodiazepine receptor activity is a reliable marker of neuronal integrity in the cortex, and movement of water molecules in the extracellular space might be a more variable indicator of tissue damage.