Analysis of our substantial single-center cohort of patients who underwent CTP imaging revealed three key findings. First, patients with successful yet incomplete angiographic recanalization experience a disproportionately negative impact from higher HIR, indicating deteriorating tissue-level collateral quality, and from increasing early infarct volume compared with those completely recanalized. Second, the benefit from complete recanalization diminishes to insignificance in patients with good collateral circulation. Finally, the benefit derived from complete recanalization becomes even more pronounced with an increase in the early infarct volume.

As anticipated, in patients with a reperfusion score of TICI 2b, lower HIR was independently associated with significantly improved functional outcomes at 90 days, although such an effect was not observed in the TICI 2c/3 group. Our findings underscore the intricate relationship between cerebral tissue-level collaterals and hemodynamics with the final angiographic outcome. In cases where collaterals are compromised, the prognosis of patients with incomplete recanalization deteriorates markedly, as the restoration of blood flow is incomplete, leading to eventual infarction of tissue reliant on insufficient supply from poorly developed collaterals. Conversely, well-functioning collaterals can sustain ischemic tissue, thereby diminishing the benefits of TICI 3 reperfusion [5]. This observed disparity offers new insights into the interpretation of tissue-level collaterals indicated by HIR in the context of the extent of patient revascularization and should be considered in future trials focusing on cerebral collateralization in endovascularly treated patients.

The findings presented align with those of a previous study that demonstrated the relevance of HIR in predicting both functional outcome and the formation of malignant cerebral edema in patients who did not achieve successful recanalization, specifically those with TICI ranging from 0 to 2a [19]. Our results can be viewed as an extension of this prior study, focusing specifically on patients in whom the procedure was deemed "successful". Furthermore, we offer clinically pertinent insights indicating that a large proportion of patients with TICI 2b still achieve a good functional outcome, particularly if they exhibit good collateral circulation. Importantly, when patients were stratified into subgroups based on dichotomization set at an HIR level of 0.3, it was evident that in the subgroup with good collateralization, the benefit from TICI 2c/3 over TICI 2b did not reach significance, in contrast to the group with poor collateralization. A similar relationship was recently reported, although the authors used manual assessment of collaterals, which involves time-consuming evaluation and inherently introduces inter-rater variability [20].

The findings described here have direct implications for clinical practice. When a patient exhibits particularly robust collaterals, as indicated by an HIR < 0.3, achieving a final recanalization score of TICI 2b is non-inferior to achieving TICI 3 in terms of functional outcome. Therefore, in such cases, our evidence supports the consideration of concluding the procedure without justification for a higher number of passes of MT devices or prolongation of the procedure, both of which are known to have adverse effects on functional outcomes and increase the risk of hemorrhage [21, 22]. Additionally, the benefit derived from TICI 3 recanalization diminishes with the number of MT maneuvers, and it has been demonstrated that outcomes after the third retrieval attempt are comparable to those of first-pass TICI 2b [6]. In conjunction with our findings, this suggests that performing additional thrombectomy maneuvers may be clinically futile, particularly in patients with optimal tissue microperfusion.

Notably, in our study, tissue-level collateralization was not directly associated with the final angiographic result itself, contrary to a previous report indicating a higher likelihood of complete recanalization in patients with good arterial collaterals [23]. This difference may stem from the use of a different collateral marker in our study, which focused more on tissue-level hemodynamics than visible leptomeningeal collateralization. Furthermore, this discrepancy may also be attributed in part to the broader inclusion criteria in our study, as we included patients presenting with occlusion localized in the M2 segment of the middle cerebral artery. However, the impact of collateral hemodynamics on the achievement of complete recanalization warrants further exploration.

The observation of a disproportionately higher impact of early infarct volume on the functional status of patients with a TICI 2b recanalization score can be interpreted from two perspectives. First, it underscores the prognostic significance of early infarct volume in such patients, with the benefit from MT decreasing markedly as infarct size increases—a trend that is considerably less relevant for patients with a TICI 2c/3 score. However, it is important to acknowledge the challenges associated with interpreting early infarct volume, often referred to as "ghost infarct core" which tends to occur in patients imaged shortly after symptom onset [24]. To address this issue, we chose to include only patients presenting more than 90 min from their last known well time, as this subgroup has been shown not to present significant ghost infarct core phenomenon [11].

Conversely, the reported relationship offers illuminating insights into the ongoing debate regarding whether high recanalization scores confer greater benefits in patients with large infarct cores upon admission. Indeed, our findings suggest that the benefit may be at least noninferior with increasing early infarct volume. However, this observed effect contrasts with the results of a previous study where the authors reported no significant functional benefit between TICI 3 and TICI 2b in patients with large infarct cores. It is important to note that in that study, a large core was defined using the ASPECTS score of 3–5 [25], which may not provide as precise information on cerebral tissue viability as perfusion imaging. Importantly, only 80 patients in our study cohort presented with early infarct volumes large enough to be considered substantial (≥ 50 mL). Thus, statistical robustness of that finding cannot be considered sufficient. Consequently, further studies are warranted to conclusively determine whether such benefits indeed exist.

Additionally, our results revealed lower frequency of the first pass effect with concomitant more frequent combined approach to the MT procedure in TICI 2b group. Such results were expected, as the poorer recanalization outcome is usually associated with higher recanalization attempts [23]. Moreover, in our Center first-line approach to the thrombectomy in the great majority of cases is thromboaspiration; stent-retriever attempts are performed afterwards the aspiration maneuver fails. Thus, as the first-pass effect was observed predominantly in the TICI 2c/3 group, so was the sole thromboaspiration approach. Despite differences in intra-procedural characteristics, the groups did not differ in case of any and symptomatic intracerebral hemorrhage; the type of device used was not linked with sICH either.

Our study has several notable limitations. First, it is retrospective in nature, which may introduce inherent biases. Second, the limited number of patients with sufficient early infarct volume to be classified as "large" restricted our ability to conduct robust analyses within this subgroup. Additionally, the exact number of passes during the MT procedure was not available for all patients, preventing us from exploring its potential interplay with angiographic scores and perfusion parameters. Lastly, pre-stroke (mRS) scores were not systematically collected before 2021 and therefore could not be incorporated into our multivariate models. However, patients treated with MT at our facility typically have pre-stroke mRS scores of 0–1. The observational nature of the current study highlights the need for future randomized trials to definitively assess the impact of perfusion imaging results on the decision-making process during MT.

In summary, our study underscores the importance of considering computed tomography perfusion results, particularly focusing on tissue-level collateralization indicated by HIR, especially in decision about further optimizing the reperfusion score from TICI 2b via methods like intraarterial thrombolysis. As demonstrated, patients with good collateralization do not derive functional benefits from a TICI 2c/3 score over TICI 2b. Therefore, pursuing such a result in these patients may not be necessary.