Probability of metabolic tissue recovery after thrombolytic treatment of experimental stroke: A magnetic resonance spectroscopic imaging study in ratbrain

The effect of thrombolytic therapy on metabolic changes was studied in rats submitted to thromboembolic stroke. Reperfusion was initiated at three dif ferent time points, 1.5, 3, and 4.5 hours after embolism (n = 3 each), by i njection of recombinant tissue-type plasminogen activator (rt-PA). Recovery was observed during 5 hours of reperfusion using perfusion-weighted images and a two-dimensional H-1 magnetic resonance spectroscopic imaging (MRSI) technique. Temporal evolution of the cerebral metabolites lactate and N-ace tyl-aspartate (NAA) was determined. To analyze the chances of metabolic tis sue recovery, the outcome of treatment, defined by a reversal of lactate co ncentration, was compared with the lactate intensity before treatment. In u ntreated animals (n = 4), clot embolism resulted in a drop of perfusion sig nal intensity in the occluded hemisphere followed by an increase of lactate concentration and a decrease of NAA that persisted throughout the observat ion period. Thrombolysis partially restored blood flow, but the mean lactat e concentration decreased only slightly after successful lysis in animals t reated 1.5 hours after embolism. If treatment was initiated later, no decli ne of lactate level was observed. Five hours after initiation of thrombolys is, the average tissue lactate amounted to 95 +/- 6, 111 +/- 17, and 139 +/ - 60% of the early ischemic value (40 minutes after embolization) if treatm ent began 1.5, 3, and 4.5 hours after embolism, respectively. The NAA level declined slightly but never showed a recovery after rt-PA treatment. In in dividual pixels, the probability of metabolic tissue recovery clearly decli ned with increasing lactate concentration before thrombolysis. Interestingl y, this probability was independent of treatment delay, but the number of p ixels with low lactate declined with increasing ischemia time. Potential cl inical applications of MRSI include monitoring of therapeutic intervention as well as support for prognosis of outcome after rt-PA treatment.