Diffusion lesion reversal

Much debate exists over the accuracy of the acute DWI lesion identifying the ischaemic core, that is, tissue that is irreversibly damaged. There is no doubt that diffusion lesions may be partially reversed with early reperfusion. This has been demonstrated in both animal and human stroke (Chalela et al. 2003 Kidwell et al. 2000 Li et al. 1999,2000). However, in humans these lesion reversals in most instances are only minor or partial, and are quite often not permanent. Indeed, in our thrombolytic series, less than 5% of patients had what would be considered any significant reduction in ischaemic lesion volume between the pre-treatment DWI and outcome T2-weighted... 

It has been proposed that the phenomenon of DWI lesion reversal means that patients without perfusion-diffusion mismatch may still benefit from thrombolytic therapy (Kidwell et al. 2000). However, others consider more research is needed before adopting such an approach into clinical practice (Schellinger et al. 2003). We have not found that non-mismatch patients benefited from thrombolysis compared to historical controls (Parsons et al. 2002a). The ongoing Australasian Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) has been designed, in part, to answer the question of whether non-mismatch patients benefit from thrombolysis (Parsons et al. 2002a). 

OUvot, J.M., et al., Relationships between cerebral perfusion and reversibility of acute diffusion lesions in DEFUSE insights from RADAR. Stroke, 2009. 40(5) p. 1692-7. 

It is important to note that this trial is not using perfusion-diffusion mismatch to select patients, but as a surrogate outcome measure. The rationale for this is that the mismatch hypothesis, whilst strongly supported by much data, remains unproven. Similarly, it is not yet established that patients with nonmismatch do not respond to thrombolysis (as there is at least a theoretical possibility of partial DWI reversal). Should either the mismatch hypothesis and/or the hypothesis that a large acute DWI lesion predicts ICH be proven in this trial, a logical next... 

Fig. 4.13. Lesion evolution in reversible (90-min) middle cerebral artery occlusion (MCAO) in a rat. Upper row, quantitative images of the apparent diffusion coefficient (ADC) lower row, quantitative T2 images as measured serially over 22 days post stroke. Note the transient pseudo-normalization of the diffusion disturbance upon reperfusion and, second, after 7 days when initially reduced ADC values slowly shift to supernormal levels indicating the chronic infarct stage. [Reproduced with permission from Hoehn et al. (2001)]...

Fig. 4.14. Maps of the apparent diffusion coefficient (ADC) measured before and after embolic occlusion of the right middle cerebral artery in an animal without therapy (upper row) and in two animals with thrombolytic treatment initiated 1.5 h (middle row) and 4.5 h (lower row) after onset of ischemia. In the untreated animal, a decline of ADC was observed immediately after MCA occlusion that increased in size over time. Thrombolysis with recombinant tissue-type plasminogen activator (tPA) lead to the partial reversal of the ADC lesion over the first 5 h of therapy if started early. Late-onset thrombolysis at 4.5 h post occlusion did not reverse lesion growth, but was followed by a further lesion enlargement of the ischemic lesion. [Reproduced with permission from Hoehn et al. (2001)]...

Decreased diffusion in nonvascular region Increased glucose utilization leads to energy failure Elevated perfusion Lesions are reversible... 

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