Diffusion-perfusion mismatch

The first of these hypotheses has been supported by several studies showing that infarcts tend to grow into the area of diffusion-perfusion mismatch, and that... 

The second hypothesis, that patients should be selected for thrombolysis depending on whether or not they exhibit a diffusion-perfusion mismatch, may have enormous implications for stroke therapy in the near future, and is one of the most actively investigated and debated subjects in neuroimaging. 

However, several important studies have shown that intravenous thrombolysis may be beneficial more than 3 hours after stroke onset, provided that only patients with a significant diffusion-perfusion mismatch are treated. In one such smdy, Ribo et al. found that patients with a significant diffusion-perfusion mismatch could be treated safely and effectively in the 3-6-hour time period. In phase II of the desmo-teplase in acute stroke (DIAS) trial, patients with diffusion-perfusion mismatch were treated with desmoteplase up to 9 hours after stroke onset, and showed better outcomes than patients given placebo, with only a minimal incidence of symptomatic hemorrhage. Similar success was achieved in the same time window by the dose escalation study of desmoteplase in acute ischemic stroke (DEDAS). ... 

These studies raise the possibility that, one day, imaging-based treatment protocols may allow for intravenous thrombolysis in patients well outside of the now-accepted 3-hour window, provided they demonstrate substantial diffusion-perfusion mismatch. Such protocols could allow for treatment of a vastly larger number of patients than are currently treated. It has been estimated that only 1-7% of acute stroke patients currently receive thrombolytic medication, and that, in up to 95% of cases, they are ineligible because they present outside of the 3-hour time window. As many as 80% of patients who present 6 hours after stroke onset may demonstrate a significant diffusion-perfusion mismatch. "... 

The echoplanar imaging thrombolysis evaluation trial (EPITHET) is the first large study designed specifically to assess whether the existence of a diffusion-perfusion mismatch should be an eligibility criterion for thrombolysis. 

Preliminary results published by the EPITHET investigators failed to show a significant correlation between the volume of diffusion-perfusion mismatch and the extent of infarct expansion. The study is ongoing at the time of this writing. 

In one study, patients with significant diffusion-perfusion mismatch on MRI, large vessel occlusive disease, and fluctuating neurological deficits were found to be more likely to respond. Induced hypertension correlated with improved cortical cerebral... 

Krishnamurthy S, Tong D, McNamara KP, Steinberg GK, Cockroft KM. Early carotid endarterectomy after ischemic stroke improves diffusion/perfusion mismatch on magnetic resonance imaging report of two cases. Neurosurgery 2003 52 238-241 [discussion 242]. 

The DIAS, DEFUSE and EPITHET studies were small and used different thrombolytic agents (and different doses in DIAS), and further studies are needed before it is certain that diffusion-perfusion mismatch on MRI is a reliable surrogate for the presence of a penumbra that might benefit from thrombolysis beyond the three-hour time window. 

Messe SR, Kasner SE, Chalela JA et al. (2007). CT-NIHSS mismatch does not correlate with MRI diffusion-perfusion mismatch. Stroke 38 2079-2084... 

With MRI, there is often a volume mismatch between tissue showing reduced water molecule diffusion (a signature for cell swelling and ischemic tissue) and a larger area of compromised tissue perfusion early after stroke onset - the so-called diffusion/perfusion mismatch. The difference, at least for all practical purposes, is believed to reflect the ischemic penumbra [138, 148-151]. Perfusion MRI currently affords a relative, rather than absolute, quantitative measure of cerebral tissue perfusion. Many studies have shown that the MRI-documented mismatch volume shrinks over time. However, mismatch may persist, for example those who present beyond 3 h and still have substantial mismatch [152], suggesting a longer window of therapeutic opportunity in select patients. 

L, Sorensen AG, Singhal AB. Stability of large diffusion/ perfusion mismatch in anterior circulation strokes for 4 or more hours. BMC Neurol. 2010 10 13... 

Copen, W.A., et al., Existence of the diffusion-perfusion mismatch within 24 hours after onset of acute stroke dependence on proximal arterial occlusion. Radiology, 2009. 250(3) p. 878-86. 

Kane, 1., et al., Comparison of 10 different magnetic resonance perfusion imaging processing methods in acute ischemic stroke effect on lesion size, proportion of patients with diffusion/perfusion mismatch, clinical scores, and radiologic outcomes. Stroke, 2007. 38(12) p. 3158-64. 

Fig. 8.9 Diffusion-perfusion mismatch. The patient is a 58-year-old woman with 5 h of slurred speech and right hemiparesis. The DWI image shows a small infarct in the left caudate nucleus and corona radiata. CBV is mildly elevated within the infarct, and within a much larger region of the left MCA territory (arrows on...

A number of studies have shown that infarcts tend to grow into the region of diffusion-perfusion mismatch, and that patients with larger mismatches tend to demonstrate more infarct growth. These studies have been performed using various different PWI-measured parameters to define the ischemic penumbra, including MTT [57-59], TTP [55, 60], CBF [56], and a nondeconvolution-based numerical approximation of MTT [61],... 

The second prediction, that the diffusion-perfusion mismatch might be used to select acute stroke patients for thrombolytic therapy, is a compelling one that has generated a great deal of scientific debate and multiple clinical trials. Underlying this interest is the unfortunate fact that, although intravenous thrombolytic therapy is the most widely available treatment for acute stroke, only 1-7% of acute stroke patients receive it [62-65]. This is largely because the decision of whether or not to... 

Most of the studies that have addressed the hypothesis that the diffusion-perfusion mismatch can be used to select patients for thrombolysis have done so indirectly, by using the existence of the mismatch to widen, rather than replace the temporal window for treatment. The traditional 3-h window is based on several early clinical trials, in which thrombolysis was effective when administered to patients who were last seen without symptoms less than 3 h before treatment [69], but did not improve in outcomes when admiifistered after up to 5 [70] or 6 [71, 72] hours after onset. These studies did not use DWI or PWI, requiring only a noncontrast head CT examination to exclude the possibility of hemorrhage before thrombolysis could be initiated. A subsequent trial, which also did not incorporate DWI or PWI, found that thrombolysis could be effective up to 4.5 h, and this result has been used to widen the therapeutic window to 4.5 h at some centers [73]. 

Support for the potential role of PWI in selecting patients for intravenous thrombolysis has come from several studies in which thrombolysis was found to be effective later than 4.5 h, if offered only to patients with a large-enough diffusion-perfusion mismatch. One such study required at least a 50% mismatch between lesions seen on DWI and TTP maps, and found that thrombolysis could be effective up to 6 h [74]. In the Desmoteplase In Acute Ischemic Stroke (DIAS) and Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS) trials, thrombolysis was effective in patients presenting 3-9 h after onset, if offered only to those with at least a 20% mismatch between lesions seen on DWI, and on pseudo-MTT maps that were created using the normalized first... 

There is solid empirical evidence that the existence of a diffusion-perfusion mismatch predicts a greater likelihood of infarct growth. Some studies, but not others, have successfully used the existence of a mismatch to select patients for thrombolysis. In evaluating the findings and implications of the many studies of PWl in acute stroke, it is important to consider the many different ways in which raw PWI images have been post-processed to yield different perfusion maps and some of the technical pitfalls that can lead to artifactual and potentially misleading results. Some of these are summarized in Table 8.3. 

In a prospective study designed to study the effect of normobaric oxygen, patients underwent a diffusion/ perfusion imaging at study entry, at 4 h and at 24 h after the initial study. A final foUow-up scan was performed 1 week later. Fourteen patients with ICA and/or proximal MCA occlusion and a diffusion/perfusion mismatch... 

The stability identified in these patients was most likely due to excellent collateral circulation in these patients. Patients with excellent collateral circulation were selected through the inclusion criteria of the study. To be eligible for inclusion, patients had to be outside the therapeutic window for tPA, and not eligible for intra-arterial thrombolytic therapy. The other major criterion was that the patient had to have a large diffusion/perfusion mismatch. These two criteria resulted in the selection of patients with relatively... 

The idea that the identification of a proximal occlusion by CT or MR angiography and the presence of a relatively small DWI abnormality could predict a significant DWI/PWI mismatch was reported by Hakimelahi et al. [39]. The investigators prospectively identified 57 consecutive patients who underwent DWI/PWI within 24 h of stroke onset, and who had terminal ICA and/or proximal MCA occlusions. They found that all patients with a DWI lesion of less than 70 mL had a diffusion/perfusion mismatch of 100% or greater (Figs. 9.1-9.9). The DWI lesion... 

MTT) maps demonstrated delayed transit time in almost the same area as the diffusion abnormality, indicating no significant diffusion/perfusion mismatch, (g, h) FoUow-up MRI showed no significant enlargement of the initial lesion... 

Hakimelahi R, Yoo AJ, Rost NS et al (2010) Prediction of a large diffusion/perfusion mismatch by the presence of a small diffusion abnormality in the setting of a distal ICA or proximal MCA occlusion. European congress of radiology, Vienna, Austria doi 10.1594/ecr2010/C-2613... 

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