Blood-brain barrier profile pretreatment is associated with hemorrhagic transformation after endovascular reperfusion

Abstract

Background: While advances in endovascular thrombectomy (EVT) have led to high reperfusion rates, most patients treated with EVT do not avoid disability. Post-reperfusion hemorrhagic transformation (HT) is a potential target for improving outcomes. This study examined pretreatment blood-brain barrier (BBB) disruption in tissue that would subsequently become part of the final infarct to evaluate its role in post-EVT HT.

Methods: This post hoc analysis of the FRAME study, which enrolled patients with anterior large vessel occlusion who received EVT within 6 hours of onset, included patients if they had successful pretreatment MRI perfusion weighted imaging (PWI) and underwent successful EVT. BBB disruption was measured as the percent signal change due to gadolinium leakage on the PWI source images prior to thrombectomy. Mean permeability derangement (MPD) was defined as the average of all voxels in the stroke core that are two standard deviations above normal. The primary outcome was hemorrhagic transformation with parenchymal hematoma (PH).

Results: In total, 164 patients were included; mean age was 71 and 48% were female. PH occurred in 57 patients. Median MPD was 13.5% for patients with PH versus 3.6% for patients without (p < 0.0001). Elevated MPD was independently associated with PH with a 20% increased risk of PH for each 5% increase in MPD (OR 1.206; 95% CI 1.037:1.405; p = 0.0147, adjusted for NIHSS and procedure duration).

Conclusions: Even in patients who are successfully recanalized in an early time window, pretreatment BBB disruption in regions that go on to infarct is associated with an increased risk of post-EVT HT.

Figure 1

Flowchart demonstrating which patients from the FRAME study were included in the analysis.

Figure 2

The pretreatment and posttreatment imaging for three patients with MPD > 20% is shown. The left column shows the PWI source image prior to treatment. The middle column shows the BBB heatmap generated from the pretreatment PWI overlain on the PWI source image. The column on the left shows the follow‐up gradient echo imaging demonstrating the location of hemorrhagic transformation. Regions of with severe BBB disruption (red on the BBB color code) show most HT on follow‐up imaging. Of note, PH is defined based on the presence of hematoma and mass effect and not on the size of the lesion.

Figure 3

The ROC curve for predicting PH with MPD showing several MPD thresholds and the corresponding sensitivity and specificity values.