Do FLAIR Vascular Hyperintensities beyond the DWI Lesion Represent the Ischemic Penumbra?

Discussion

The present study revealed 3 salient points: 1) FVHs were consistently visualized in the insular region in patients with proximal MCA occlusion within 4.5 hours after symptom onset; 2) FVH-DWI mismatch was associated with a smaller initial infarct, the presence of PWI-DWI mismatch, and greater infarct growth after thrombolysis even though their final infarcts remained smaller; and 3) FVH-DWI mismatch predicted a large PWI-DWI mismatch with excellent sensitivity but moderate specificity.

The high prevalence of FVHs irrespective of their location is likely explained by the fact that patients were imaged within 4.5 hours and had proximal MCA occlusion. Indeed, a lower FVH prevalence has been reported in posterior strokes and in distal occlusions² or when onset-to-MR imaging time increased.^1,17 Like others,^10,20 we found fewer FVHs in borderzone areas (M4, M6) than in more proximal areas (insula, M2, M5). This FVH gradient is consistent with an increasing flow rate within leptomeningeal collaterals when moving toward borderzone areas.

Several approaches have been proposed to estimate the extent of FVHs. Some authors distinguished FVHs involving more or less than one-third of the MCA territory or of the hypoperfused area,^3,6,21 but one has to acknowledge the well-known difficulties in determining this cutoff. Others proposed to count ASPECTS regions with FVH-matching boundaries^10,20 or grade FVHs according to their sulcal location,²² without evaluating the reproducibility of these grading systems. Counting the number of axial FLAIR sections with FVHs⁵ only provides a rostrocaudal extension of FVHs and is dependent on the section number and thickness. FVH-DWI mismatch offers several advantages over previous estimates of FVH extent. It is simple, reproducible, and feasible at bedside and therefore compatible with timely treatment decisions in acute stroke. The FVH-DWI mismatch focuses on FVHs beyond the boundaries of the cortical DWI lesion, ignoring FVHs adjacent to the DWI lesion. Therefore, only FVHs facing potential tissue at risk of infarct expansion are considered in this definition. The presence of larger amounts of at-risk tissue in the presence of FVH-DWI mismatch is also supported by the results of our univariate analysis, with smaller initial DWI lesions and larger infarct progression after treatment, despite a similar rate of complete recanalization in both groups. These results closely match those from a previous series of 52 patients treated with thrombolysis for MCA occlusion.³ Similarly, others concluded that the extent of FVHs was associated with the presence of a PWI-DWI mismatch, though the definition used for the latter was qualitative¹³ or unspecified.^8,10 Taken together with these previous findings, our results in turn reinforce the view that FVHs beyond the DWI lesion represent markedly impaired hemodynamics in patients with proximal occlusion.

The excellent sensitivity (92%) of FVH-DWI mismatch for a large PWI-DWI mismatch indicates that the former only rarely missed the latter. This could indicate that the absence of FVH-DWI mismatch may obviate PWI to identify patients with large penumbra. However, the moderate specificity (64%) means that FVH-DWI mismatch as implemented here captures hemodynamic compromises other than just the penumbra. Indeed, if bright vessels on FLAIR effectively represent slow flow in dilated leptomeningeal arterioles in response to cerebrovascular autoregulation, FVHs should overlie not just the penumbral cortex but also the less severely hypoperfused, not at-risk tissue (ie, the “benign” oligemia) and even perhaps surrounding normoperfused but autoregulated tissue.²³ This hypothesis was strengthened by the post hoc use of a deliberately defined less conservative Tmax threshold (>4 seconds). As expected, specificity increased while sensitivity held up, compared with the standard Tmax of >6 seconds. Thus, FVHs beyond the DWI lesion likely detect not just penumbral but also less severely hypoperfused areas. One should, however, keep in mind that the optimum Tmax cut-point separating the penumbra from the oligemia remains somewhat unclear.²⁴ However, even though the FVH-DWI mismatch likely overestimates the penumbra, it could serve as a surrogate for PWI-DWI mismatch whenever PWI is unavailable or degraded by artifacts or patients have difficult venous access or contraindications for gadolinium use such as renal failure or contrast hypersensitivity.

Our retrospective study has several limitations. First, our results cannot be generalized to all patients with stroke, especially those with no or distal occlusion. However, we deliberately selected a population of patients with proximal MCA occlusion and visible anterior cerebral artery origin to ensure homogeneity of the potential collateral supply, given the discrepant FVH findings in previous more heterogeneous populations. Second, we were unable to correlate FVHs with collateral flow because patients did not undergo digital subtraction or CT angiography. Third, we defined the PWI-DWI mismatch on the basis of stringent DEFUSE 2 criteria. The accuracy of the FVH-DWI mismatch as a surrogate for PWI-DWI mismatch obviously depends on the definition of the latter, which is still debated. Fourth, slight differences in FLAIR parameters among patients in our study are unlikely to have induced major variability in FVH detection. We must, however, be careful in drawing any definite conclusion because differences in the FLAIR sequence, coil system, and magnetic field or among manufacturers may influence FVH visibility.