CE was commonly found on NCCT obtained immediately after EVT in patients with AIS3,4,5,6,7,8,9,10which has been attributed to disruption of the blood-brain barrier4,11,12,13. In the present study, the incidence of CE on NCCT was 71.5%, which was comparable to previous reports (30.7–87.5%3,4,5,6,7,8,9,10). Our work is novel in that we adapted the ASPECTS score methodology to CE combined with volume measurement to assess the extent and location of CE, and found that CE based on this quantitative method after EVT was an independent and powerful predictor of clinical functional outcome after excluding certain hemorrhage by control CT at 24 h.
Previous studies have investigated the relationship between hyperdensity on the NCCT and clinical outcomes, but the results were conflicting. Some studies have shown that the presence of a high density lesion on the NCCT has no prognostic value on clinical outcomes8,9,10. On the other hand, Portela et al.3 found that the total size of the hyperdense zone had a positive correlation with the mRS at 90 days after EVT. As stated previously, hyperdensity may be related to contrast agent, hemorrhagic transformation, or a combination9,11,13,17, which can be caused by varying degrees of BBB disruption. Based on dual-energy CT (DECT) technology, which enables precise differentiation between contrast staining and hemorrhage, Renú et al.4 and Chen et al.5 reported that contrast staining within 24 h of EVT was associated with an increased risk of bleeding and was also an independent predictor of adverse clinical outcomes. The definitions of hyperdensity in these studies were of two kinds: strong attenuation and contrast staining, depending on whether or not it contained hemorrhage. We speculate that the controversial results of these studies may be related to the following reasons: the heterogeneous definitions of hyperdensity based on the different computed tomography techniques after EVT (high attenuation on NCCT3,8,9 vs contrast staining on DECT4,5,10), or the absence of a quantitative assessment (quantitative3 vs non-quantitative4,5,8,9,10).
We adapted the methodology of the ASPECTS score to CE combined with volume measurement by 3D reconstruction to ensure an accurate assessment of the extent and location of CE on the NCCT obtained immediately after EVT. To our knowledge, this is the first report describing this technique in the evaluation of CE after EVT. Although DECT is considered the gold standard for differentiating contrast agent extravasation and cerebral hemorrhage after EVT, with high sensitivity and specificity4,5,18,19,20, it is not readily available in most stroke centers. Moreover, since hemorrhagic transformation has been found to be associated with poor functional outcome in AIS-LVO patients in previous studies, particularly PH2 (>30% of infarcted area with an occupancy effect of significant space)21,22,23, we explored the relationship of CE on NCCT with functional outcome after excluding cases with definite hemorrhagic transformation. Interestingly, the presence of CE in the caudate region, M2, M4, M5, and M6 was significantly related to poor outcome, which may be explained by the fact that these cortical regions of ASPECTS contained eloquent brain functional areas involving the premotor, motor and parietal cortex. Another possible explanation is that the presence of CE in cortical areas may be associated with poor collateral circulation, which was an independent predictor of poor clinical outcome in acute ischemic stroke.24,25,26,27,28. The other possibility may be associated with pre-existing early infarction prior to EVT, which was supported by the correlation between CE-ASPECTS scores and baseline ASPECTS of infarct lesions in this study (ρ = 0.31 ; P13,16,29.
We acknowledge the limitations of our study. A main limitation is that a follow-up CT 24 h after EVT is needed to exclude hemorrhage in the current study, which will limit the clinical value of the current findings. However, the current results will be useful for patients whose contrast enhancement after EVT can be assessed without the need for a CT scan 24 h after EVT. On the other hand, the current results will provide important information for patients with contrast enhancement after VTE whose hemorrhage has been excluded by early DECT. Second, data based on a relatively small sample size and a single medical center were susceptible to selection bias. A larger sample of patients can further refine the model. Due to the retrospective nature of the present study, potential confounders could not be fully controlled. Third, the dose of the contrast agent was not collected in this study due to the retrospective design. It has been reported that high amounts of contrast agent could be a potential contributor to BBB disruption due to its toxicity5,11,30and can lead to the neurological complications of contrast-induced encephalopathy30.31. In the present study, comparable procedure time and stent retriever passages between groups may indirectly rule out the effect of CE quantity. Fourth, we did not record the number of microcatheter injection cycles achieved, which is also known to be associated with contrast extravasation and intracranial hemorrhage.32. Finally, since the present study focused on the effect of CE on clinical outcomes, patients with hemorrhage defined on the NCCT immediately after EVT were excluded to avoid the confounding effect, our conclusion therefore does not apply to patients with hemorrhagic transformation.