Hyperintense Vessels on FLAIR: Hemodynamic Correlates and Response to Thrombolysis

Discussion

The extent of FHV is not only associated with larger perfusion deficits^1,16 but is also an independent predictor of more severe hypoperfusion, resulting in larger infarct growth. Although we found no independent association between the extent of FHV and functional recovery, the severity of hypoperfusion was independently associated with a worse functional recovery 3 months poststroke (Table 2).

Similar to results from a multicenter observational study,¹² approximately 87% of patients with proved vessel occlusion had at least 1 section with FHV on acute examination. Patients with extensive FHV (>4 sections) had comparatively higher NIHSS scores on admission, more severe hypoperfusion, larger infarct growth, and a worse functional outcome 3 months poststroke. While patient groups based on FHV differed in terms of stroke etiology, TOAST criteria showed neither association with the severity of hypoperfusion nor functional recovery in univariate analysis.

Bang et al¹¹ used the same Tmax HIR ratio to determine the severity of the perfusion deficit and found similar results in terms of NIHSS scores on admission and infarct volume. Most interesting, this study found that low HIR (moderate hypoperfusion) was highly associated with good collateral grades. This finding is in line with our hypothesis that FHV are indicative of severe hypoperfusion and insufficient collateralization. These results stand in contrast to previous studies suggesting that FHV represent increased leptomeningeal collateralization^6,7,10,17; these studies, however, did not report perfusion status or clinical follow-up.

Peripheral collateralization is an inherent defense mechanism following proximal vessel occlusion; collaterals can prolong tissue viability if blood flow is sufficient to keep hypoperfusion moderate until reperfusion is achieved. Vessels become hyperintense on FLAIR when blood flow is so slow that there is a loss of the flow-void phenomenon. Here, we observe an independent association between the extent of FHV and severe hypoperfusion (Table 3); however, the link to collateral flow is not yet clear. On the one hand, one might imagine that slow flow in collaterals directly causes arterial hyperintensities on FLAIR, suggesting that FHV directly depict insufficient or sluggish flow in collateral pathways.^7,8 On the other hand, vessel occlusion and subsequent ischemia cause cerebral swelling, which likely compresses distal collateral vessels, slowing blood flow. Regardless, FHV most likely reflect slow flow in distal collateral pathways distributed over a large ischemic area, resulting in larger ischemic lesions. Hence, this frequently observed MR imaging feature may be useful as a tool to assess the severity of hypoperfusion over an ischemic area as a result of poor collateralization.

Of note, patients with large-vessel occlusion had less pronounced FHV (<4) and more moderate hypoperfusion (low HIR), though these did not reach the level of significance (Tables 1 and 2). Carotid occlusions are frequently the end result of chronic occlusive disease, and the recruitment of collaterals often happens before acute stroke takes place. Thus, one might imagine that the longer large-vessel disease has been in existence before the index event, the greater the likelihood of excellent flow in collaterals. These collaterals might maintain good flow without visible FHV; however, this is mere speculation.

Although HIR was an independent predictor of functional recovery, we observed no independent associations of the extent of FHV and outcome (Table 4). A possible explanation may lie in the heterogeneity of vessel occlusion size observed in this cohort; an independent analysis including only patients with middle cerebral artery occlusions is suggested.

In multivariate analysis for outcome, baseline lesion volume remained in the model, accounting for 21% of the variance; this is to be expected because initial infarct volume may reflect collateral status. While FHV may be indicative of insufficient collateral flow, the clinical relevance of this MR imaging sign in terms of predicting response to treatment remains unclear. A study by Olindo et al⁹ found extensive FHV associated with smaller infarcts pre- and posttreatment, as well as a better prognosis in patients with MCA occlusion. The discordance of these results may lie in the use of different MR imaging units (1T versus 3T), the characteristics of populations studied, and the question at hand. In this study, we focused primarily on the acute hemodynamic correlates of FHV, which show a clear independent association with more severe hypoperfusion; the prognostic value of FHV remains unresolved.

Most interesting, smoking was independently associated with moderate hypoperfusion, suggesting better collateralization in patients with this risk factor. Bang et al¹¹ also found an association between smoking status and low HIR. Studies have suggested that long-term smoking-induced atherosclerosis leads to increased collateralization,¹⁸ which may explain this observed phenomenon.

This study has limitations. Most important, it is a retrospective observational study. Furthermore, lack of DSA did not allow direct assessment of collateral grade; the use of HIR only partially compensated for this limitation. Finally, due to small numbers, this study runs the risk of type 2 errors, and multivariable regression analyses may lead to overfitting.