Thrombolytic reversal of acute human cerebral ischemic injury shown by diffusion/perfusion magnetic resonance imaging

Abstract

Diffusion magnetic resonance imaging provides an early marker of acute cerebral ischemic injury. Thrombolytic reversal of diffusion abnormalities has not previously been demonstrated in humans. Serial diffusion and perfusion imaging studies were acquired in patients experiencing acute hemispheric cerebral ischemia treated with intra-arterial thrombolytic therapy within 6 hours of symptom onset. Seven patients met inclusion criteria of prethrombolysis and postthrombolysis magnetic resonance studies, presence of large artery anterior circulation occlusion at angiography, and achievement of vessel recanalization. Mean diffusion-weighted imaging lesion volume at baseline was 23 cm3 (95% confidence interval [95% CI], 8-38 cm3) and decreased to 10 cm3 (95% CI, 3-17 cm3) 2.5 to 9.5 hours after thrombolysis. Mean apparent diffusion coefficient lesion volume decreased from 9 cm3 (95% CI, 2-16 cm3) at baseline to 1 cm3 (95% CI, 0.4-2 cm3) early after thrombolysis. A secondary increase in diffusion volumes was seen in 3 of 6 patients at day 7. In all 4 patients in whom perfusion imaging was obtained before and after treatment, complete resolution of the perfusion deficit was shown. Diffusion magnetic resonance signatures of early tissue ischemic injury can be reversed in humans by prompt thrombolytic vessel recanalization. The ischemic penumbra includes not only the region of diffusion/perfusion mismatch, but also portions of the region of initial diffusion abnormality.

Evolution of lesion volume in acute stroke treated by intravenous t‐PA

“…In contrast to other studies (8,9), very little normalization was observed at day 1 in this population, which received thrombolytics. Globally, a significant increase of DWI lesion volumes appears from day 0 to day 1.…”

“…The mismatch model assumes that the initial diffusion lesion represents irreversibly infarcted core tissue. However, human and experimental studies have demonstrated that diffusion lesions may be reversible when reperfusion occurs rapidly (1,8,26). The aim of our study was to analyze the course of the lesion volumes in order to provide relevant information about the evolution of the diffusion process.…”

Dynamic Functional Cerebral Blood Volume Responses to Normobaric Hyperoxia in Acute Ischemic Stroke

“…However, the merits of this technique are still debated as a result of some studies showing that DWI lesions are potentially reversible (Kidwell et al, 2000), and may comprise regions that may fulfill the PET criteria for potentially salvageable tissue (Guadagno et al, 2006). Moreover, there is ambiguity about the optimal perfusion threshold that can distinguish benign oligemia from 'penumbral' tissue (Dani et al, 2011).…”

Early Nonischemic Oxidative Metabolic Dysfunction Leads to Chronic Brain Atrophy in Traumatic Brain Injury

“…We failed to detect ischemia as the major pathologic entity underlying the metabolic dysfunction using our current approach. It is noteworthy that normalization of ADC reduction occurs in large artery strokes treated with recanalization (Kidwell et al, 2000;Kidwell et al, 2002;Fiehler et al, 2002). The extent of the correction seems to be dependent on recanalization.…”

“…Hence, a transient early ischemic event missed by our MRI imaging protocol would likely not contribute to the long-term atrophy that we report in this study. In some cases of ischemic stroke, the normalized ADC again becomes abnormal on MRI at day 7 after stroke despite early ADC normalization (Kidwell et al, 2000). Given that we imaged patients in a delayed manner in the acute setting (mean of 8 days), we theoretically would see late ADC signs of ischemia even if reperfusion had occurred after an early ischemic event.…”