Do Fluid-Attenuated Inversion Recovery Vascular Hyperintensities Represent Good Collaterals before Reperfusion Therapy?

Discussion

In a large population of patients with MCA stroke who underwent MR imaging with PWI before reperfusion therapy, we found the following: 1) FVH extent was independently associated with a low HIR (ie, proportionally milder hypoperfusion and hence good collaterals); and 2) patients with extensive FVHs more frequently experienced early neurologic improvement and excellent 3-month outcome, despite similar initial stroke severity and recanalization rates. These findings strengthen the notion that extensive FVHs represent a reliable surrogate for good collaterals, which maintain the viability of the ischemic tissue while awaiting reperfusion.

The presence of FVHs is considered a reliable marker of arterial occlusion^{7,13,23⇓–25} and, consequently, is associated with more severe admission neurologic deficits than its absence. Like others,¹⁷ we found FVHs in most patients (99%) with arterial occlusion. Besides their dichotomous presence or absence, FVH extent has been quantitated with various methods. In one method, FVHs were rated as involving less than or more than one-third of the MCA territory or the hypoperfused area,^16,19 but determining this cutoff is notoriously difficult. FVHs have also been graded according to their sulcal location²⁶ or by counting their number,¹¹ which is cumbersome in the hyperacute clinical setting. Finally, counting axial FLAIR sections with FVHs has recently been proposed,¹² but this does not account for the actual extent within each section and depends on the section number and thickness. We, like others, have previously assessed FVH topography relative to the DWI lesion, considering their rostrocaudal and anteroposterior distributions, but this approach depends on the size of the DWI lesion and does not yield the total extent of all FVHs.^9,17,20 Our simple approach overcomes most of these limitations, affords an excellent interobserver concordance, and improves feasibility relative to manually counting all FVHs for clinical implementation.

Only a few studies have focused on the significance of FVH extent in the early time window. One study did not find an association between FVH extent and clinical outcome,²⁵ while several others reported that extensive FVHs were associated with smaller baseline DWI lesions,^9,15⇓–17 larger PWI-DWI mismatch,^9,16 smaller infarct growth,^16,18,19 and better clinical outcome.^15,17,18 Similarly, we showed an independent association between extensive FVHs and a low HIR (ie, good collaterals). Patients with extensive FVHs also had a larger PWI-DWI mismatch, suggesting larger penumbra due to robust collaterals protecting the penumbra from rapidly decaying while awaiting reperfusion. Accordingly, extensive FVHs were associated with smaller ischemic lesions before treatment in patients with proximal occlusion, reinforcing our hypothesis that FVHs represent good collaterals.

The benefit of FVH-ASPECTS over simple DWI-ASPECTS for the assessment of collateral status remains to be evaluated. Most important, patients with extensive FVHs more frequently experienced early neurologic improvement and excellent 3-month outcome in contrast to those with fewer FVHs, despite more proximal occlusions and similar recanalization rates. Conversely, our findings stand in apparent contradiction to other studies suggesting that FVHs represent poor collaterals.^{7,12,13,23,24} However, these studies either dichotomously categorized patients into the presence or absence of FVHs^7,13,23 rather than analyzing FVH extent and/or were conducted in patients not eligible for thrombolysis.²⁴ These differences might explain the discrepancy with our findings. Perhaps more surprising are the results from Kufner et al,¹² who found that FVHs rather reflected poor collaterals using the HIR in patients with arterial occlusion before thrombolysis. This discrepancy might result from several differences between this study and ours. First, Kufner et al used a 3T scanner compared with 1.5T here, and the significance of FVHs may depend on magnetic field strength and sequence parameters.²⁷ Second, we studied a larger and more homogeneous population of overall severe anterior circulation strokes, as opposed to mixed anterior and posterior milder strokes in the Kufner et al study. The unreported proportion of posterior circulation strokes might have influenced their results because the reliability of HIR as a surrogate for good-versus-poor collaterals in this stroke subtype is unknown. Third, Kufner et al dichotomized their sample according to whether FVHs were visible over at least four 5-mm thick FLAIR sections, and such a cutoff might not have equal meaning for anterior-versus-posterior circulation strokes. Fourth, they merged patients with M1, M2, P1, P2, and vertebral occlusions into a single “medium vessel occlusion” group with an unreported proportion of distal occlusions.

FVHs might, however, be a marker for proximal occlusion²³ rather than an indicator of collateral flow. Distal occlusions are indeed unlikely to result in extensive FVHs, irrespective of the quality of collaterals. However, the independent association between the FVH score and the low HIR we found in the population mixing distal and proximal occlusions remained significant in the 161 patients with proximal occlusion. This strengthens the link between FVH visibility and the quality of collaterals, irrespective of the occlusion type. Finally, the definition of HIR differed between our study and that of Kufner et al¹² (Tmax 10/6 seconds here versus Tmax 8/2 seconds), but the definition we used predicted rates of collateral flow, infarct growth, and clinical outcome in the DEFUSE 2 cohort.⁶ Further studies are needed to determine which of the above differences accounts best for the discrepancy between the 2 studies.

Direct comparisons between FVH extent and DSA are limited.^10,15,26,28 Except from a seminal study in which only 8 patients underwent DSA,⁷ others consistently reported FVHs to be associated with good collaterals.^10,15,26,28 Our results are consistent with the latter DSA-FLAIR correlations. Although the HIR is an indirect marker of collateral status,^5,6 PWI is obtained within minutes of FLAIR, thereby overcoming the issue of the delay between MR imaging and DSA inherent in all MR imaging–DSA comparisons. Given the transient nature of FVHs,⁷ correlation between MR images obtained nearly simultaneously provides new insights into the debated significance of FVHs.

That numerous well-developed collaterals appear as extensive FVHs deserves attention. In ischemic stroke, FVHs are undoubtedly related to retrograde collateral flow, which reaches cortical areas later than anterograde flow, often during the venous angiographic phase. This sluggish flow likely explains, at least in part, FVH visibility.¹⁰ A recent study showed that FVHs were more prominent when the arterial circulation time on DSA was neither too short (>1 second) nor too long (<7.98 seconds).²⁸ Given that prominent FVHs are observed in a wide range of intermediate time delays of retrograde collateral filling,²⁸ FVH visibility might depend on not only flow speed but also the amount of recruitable collaterals. Extensive FVHs could reflect the recruitment of numerous well-developed collaterals from both the anterior cerebral artery and posterior cerebral arteries (which can cover the entire ischemic bed). FVHs abutting anterosuperior ASPECTS areas may correspond to leptomeningeal collaterals from the anterior cerebral artery to the MCA, and FVHs abutting posteroinferior ASPECTS areas may correspond to leptomeningeal collaterals from the posterior cerebral artery to the MCA.²⁶

This retrospective study has several limitations. First, collateral status was indirectly based on the HIR. The validity of the dichotomization at the median to categorize into good and poor collaterals can also be questioned. Our median HIR was, however, identical to that observed in the study of Bang et al.⁵ We also checked that our results were not affected by using the median HIR value of 0.4 derived from the DEFUSE 2 cohort.⁶ Second, despite similar recanalization rates in patients with low/high HIRs or in those with few/extensive FVHs, we cannot exclude some patients having futile recanalization because the latter was assessed on the 24-hour MRA. Third, our results are based on 1.5T MR imaging data from the same manufacturer with standardized parameters. Although this ensures data homogeneity, it prevents extrapolating to other magnetic fields, coil systems, or FLAIR parameters that may influence FVH visibility.²⁷ Fourth, we collapsed FVH data as a single score, assuming that each ASPECTS area had the same significance. However, FVHs in different ASPECTS locations may not share the same pathophysiology.^15,17,24,26 Further studies are needed to determine the implications of FVH location, if any. Last, most patients were treated by thrombolysis alone, following guidelines at the time they had a stroke. Although the association between the FVH score and HIR is independent of the type of treatment, the association with outcome might differ in patients treated according to current state-of-the-art guidelines. Because we found that extensive FVHs represented good collaterals, their link with early neurologic improvement and favorable outcome could be stronger if recanalization rates increase, as expected with bridging therapy.