Endovascular revascularization therapy has become the first line treatment for acute ischemic stroke (AIS) with large vessel occlusion (LVO). With modern endovascular techniques, patients can achieve over 80% successful revascularization (1–7). However, good clinical outcomes represent ~50%. Clinical outcome is affected by many factors, including time from onset to recanalization, ischemic core volume, collateral compensation status, and post-procedural management. Rapid recanalization is the critical factor for achieving a favorable outcome. In this regard, one of the most important modifiable factors is to set up an optimal endovascular strategy.

Embolic occlusion (Emb-O) and intracranial atherosclerotic stenosis occlusion (ICAS-O) are two main causes of AIS with LVO, and both of them are treated with endovascular therapy in acute settings. Unlike the case with Westerners, ICAS-O is a more common cause of AIS in Asians (8). The Chinese IntraCranial AtheroSclerosis study group determined that the prevalence of ICAS defined as a ≥50% reduction in diameter on magnetic resonance angiography was 46.6% among hospitalized AIS patients (9). Another study demonstrated that at least 25% of cases of Chinese patients with anterior circulation AIS with LVO who received mechanical thrombectomy were diagnosed as ICAS-O (10). ICAS-O leads to more cases of thrombectomy failure (11–14). The underlying stenosis cannot be solved by stent retrieval; however, the irritated endothelium after thrombectomy would result in instant spontaneous re-occlusion. Accordingly, more than one third of the cases of ICAS-O ended up with rescue technique during endovascular procedure (14), including intraarterial, or intravenous GP IIb/IIIa inhibitor infusion (11, 15), balloon angioplasty, stent retriever detachment, or another stent implantation (13, 16, 17). Thus, it is very important to differentiate ICAS-O from Emb-O before starting the procedure.

A variety of methods can be used to differentiate ICAS-O from Emb-O. Clinical history includes progressive or fluctuating symptoms, low median baseline National Institutes of Health Stroke Scale (NIHSS) score, male, hypercholesterolemia, smoking; posterior circulation involvement may possibly support ICAS-O (16, 18, 19), while atrial fibrillation strongly suggests Emb-O. Imaging features include hyper-density vessel sign on non-contrast CT scan (NCCT) (20) and susceptibility vessel sign on susceptibility-weighted magnetic resonance imaging, which are specific indications of Emb-O (21). However, the identification of ICAS-O before thrombectomy is still challenging, especially in patients with complicated clinical situations. Hereby, we propose a new method simply based on the angiographic appearance of occlusion artery with high specificity for identification of ICAS-O.

A total of 249 patients with LVO underwent thrombectomy during this period. After reviewing the images, 66 patients were excluded (49 patients did not have clear angiogram images, 13 patients had tandem disease, and 4 patients suffered severe intracranial hemorrhage and thrombectomy were ceased). A total of 183 patients were finally analyzed, 27 (14.7%) patients were under local anesthesia due to severe cardiac or pulmonary disease, 164 patients (93 males, mean age 66.8 ± 11.8 years, mean initial NIHSS 15.7 ± 7.2) achieved successful recanalization (final mTICI ≥ 2b). Among them, 42 (25.6%) suffered internal carotid artery occlusion, 98 (59.8%) had MCA occlusion, 18 (11.0%) had vertebral BAs occlusion, 40 (24.4%) were identified as ICAS-O, and 124 (75.6%) were identified as Emb-O.

Example illustrations of patients with and without jet-like appearance were shown in Figure 1. Jet-like appearance was observed in 34 (20.7%) patients. The intraobserver and interobserver kappa values for detection of jet-like appearance were 0.889 and 0.847, respectively.

As Table 1 shows, patients with jet-like appearance were younger (68.0 ± 11.9 years vs. 62.7 ± 10.2, p = 0.019), and had lower baseline NIHSS scores (16.6 ± 7.1 vs. 12.4 ± 6.5, p = 0.002). A history of past stroke and transient ischemic attack was more frequent in patients with jet-like appearance (p = 0.011), and atrial fibrillation was more common in patients without jet-like appearance (p = 0.001). Stroke etiology was distributed differently in the two groups. Cardiac embolism was the most common etiology for patients without jet-like appearance. For patients with jet-like appearance, 71.4% were classified as having large artery atherosclerosis. The ICAS-O rate was higher in the jet-like appearance group as well (82.9 vs. 8.5%, p < 0.001), and rescue methods were more frequently used, including intraarterial tirofiban infusion, balloon angioplasty, and stent placement (p < 0.001).

The proportion of jet-like appearance and ICAS-O differed according to the occlusion site (Table 2). Jet-like appearance was mostly found at the origin of the MCA (44.1%), followed by the first segment trunk of the MCA (20.6%) and the supraclinoid of the ICA (11.8%). There was no jet-like appearance in the petro-cavernous segment of the ICA. In comparison, the origin of the MCA (35.0%), first segment trunk of the MCA (25.0%) and supraclinoid of the ICA (10.0%) were the most common sites for ICAS-O.

Thus, age, baseline NIHSS score, atrial fibrillation, history of stroke/TIA, and jet-like appearance were included in a binary logistic regression model to select predictors for ICAS-O. Binary logistic regression analysis (Table 3) revealed that jet-like infusion sign was independently associated with ICAS-O, after adjusting for age, baseline NIHSS score, atrial fibrillation, and history of stroke/TIA [OR 180.813, 95% CI (17.966, 1,819.733), p < 0.001].

Diagnostic indices are shown in Table 4. The sensitivity, specificity, and accuracy values for the jet-like infusion sign for predicting ICAS-O were 73, 95, and 90%, respectively, for all patients with ICAS-O. The accuracy of predicting ICAS-O at the origin of the MCA, and supraclinoid of the M1 trunk and ICA was 96, 78, and 83%, respectively.

Here, we proposed that the jet-like appearance at an occluded artery on angiography is an independent image marker for ICAS-O. Out of all patients with LVO, jet-like appearance was detected in 73% of patients with ICAS-O, and exhibited 95% specificity for ICAS-O, suggesting that the jet-like appearance is useful for predicting ICAS-O before thrombectomy.

In our study, 24.4% of patients were determined as having ICAS-O, which was consistent with previous studies (10, 22). Patients with ICAS-O presented the same features as other studies, like younger age (17) and lower baseline NIHSS scores (16, 19). Furthermore, a history of stroke or TIA was more common among ICAS-O patients, while atrial fibrillation was more common in Emb-O patients.

Patients with jet-like appearance and ICAS-O shared similar characteristics of their medical histories and baseline NIHSS scores. After adjusting for other confounding factors, this study demonstrated that jet-like appearance before thrombectomy strongly indicated ICAS-O. Furthermore, the predictive value of jet-like appearance differed according to the occlusion site. Jet-like appearance was easily found where the occlusion occurred distal to a large branch take-off, such as the ICA supraclinoid (where ophthalmic artery take-off was performed), origin of the MCA (where ACA take-off was performed), or the fourth segment of the vertebral artery (where posterior inferior cerebellar artery take-off was performed). For occlusions occurring proximal to a large branch take-off, contrast agent was insufficient to reach the occlusion edge. This could explain why jet-like appearance was never seen in our study at the petro-cavernous segment of the ICA, where atherosclerotic stenosis frequently occurs. It also explained the low sensitivity of jet-like appearance in the trunk of the MCA first segment.

Occlusion caused by intracranial arterial dissection (ICAD) sometimes demonstrates a jet-like appearance and would be difficult to discriminate. “Intimal flap” and “double lumen” are the most characteristic findings associated with ICAD (23). However, these findings are visible in only a few cases. The “pearl and string sign” and retention of contrast media in the false lumen are often seen in conventional cerebral angiographies of ICAD. Furthermore, whether or not a fixed focal stenosis by single-stent retriever deployment in the occlusion can be the criterion for differentiating ICAD from ICAS-O.

Stent retrievers and contact aspiration devices both demonstrate significant efficacy as first line methods for mechanical thrombectomy (24). However, both are primarily designed for embolism occlusion rather than ICAS-O (7, 25, 26). Stent retriever thrombectomy often results in instant spontaneous re-occlusion due to subsequent thrombosis at the site of ICAS (11). On the other hand, contact aspiration seems less effective than stent retrievers for ICAS-O, resulting in a longer time from puncture to reperfusion, longer procedure duration, and a higher rate of switching to an alternative thrombectomy technique (27, 28). As mentioned above, ICAS-O often requires intraarterial or intravenous GP IIb/IIIa inhibitor infusion, emergent balloon angioplasty, and stenting (11, 15–17, 29). Intraarterial infusion of GP IIb/IIIa inhibitor tirofiban at the occlusion site may be a reasonable therapeutic option since the major components of thrombi in situ of ICAS are rich in platelets and fibrin. Recent studies have shown that both intracranial angioplasty/stenting and intraarterial infusion of a glycoprotein IIb/IIIa inhibitor are effective and safe in the treatment of AIS patients with ICAS-O (30). In ACTUAL study, investigators found that patients with acute anterior ICAS-O, who received primary angioplasty treatment, showed favorable independent outcomes at 90 days and lower rates of asymptomatic intracranial hemorrhage compared to patients who received primary stent retriever thrombectomy (31). All this evidence suggest that the optimal early endovascular strategy for ICAS-O is quite different than that for Emb-O. Thus, early identification of ICAS-O may help operators modify the treatment approach before initiating intervention. Operators should reduce thrombectomy passes and switch to rescue methods in a timely manner once ICAS-O is determined. However, it is difficult for operators to make accurate judgment in emergent situations due to incomplete clinical information. Coexistence of ICAS and atrial fibrillation further increases the difficulty. Deng et al. (10) determined that 8.6% of anterior circulation LVO patients who received mechanical thrombectomy had both of them. In our study, the corresponding ratio was 1.8% (3/164). Yet, all 3 patients showed jet-like appearance and were classified as ICAS-O, indicating that jet-like appearance can predict ICAS-O effectively, even in complex clinical situations.

Occlusion type is a highly specific image marker for differentiating ICAS-O from Emb-O. Truncal type occlusion during thrombectomy post-stent deployment had 87.4% specificity to predict fixed focal stenosis (32). Microcatheter first-pass effect, a string-like blood flow observed in angiography after the microcatheter is retrieved from the occlusive vessel segment, indicates ICAS-O (33). First-pass effect can accurately predict ICAS-O in 88.5% of patients with LVO (33). These methods have a few limitations despite their high specificity. The main problem is that additional manipulations are required to determine the occlusion etiology; for example, microcatheter angiography beyond the occlusion, post-deployment angiography, or repeated microcatheter movement in the occlusion. All these manipulations implied the risk of irritating the inflamed plaque in ICAS-O (34). Besides, occlusion type practically depends on stent-through blood flow and cannot be determined in patients undergoing non-stent thrombectomy. In comparison, the jet-like appearance can help interventionists identify ICAS-O before the procedure, so that they can choose the most appropriate frontline instruments and strategies. Occlusion type based on CTA was another applicable method for determining ICAS-O before thrombectomy. However, conventional CTA imaging may vary depending on whether the scan phase is arterial, arteriovenous, or venous-weighted (35, 36). Unequal CTA quality would make ICAS-O identification difficult. Multiphase CTA or CTP could resolve this shortcoming but is not available at most centers (3, 37–40).

Our study has several limitations. Firstly, this study was performed at a single stroke center, with a relatively small number of ICAS-O patients. Secondly, 49 patients were excluded because of a lack of clear angiogram images. This accounts for 26.5% and may limit the level of rigor of the data. Among them, 35 patients did not undergo a first angiography, but a roadmap was available. A roadmap often shows images of the vessels in early arterial phase for clear navigation, while occlusion edges on DSA imaging can only be observed clearly in the late arterial phase due to decreased blood flow motivation. Furthermore, a roadmap is often not available for patients undergoing local anesthesia. Therefore, in our opinion, a clear angiography including complete arterial and venous phase would be crucial for detecting jet-like appearance. The main drawback of jet-like appearance is that it relies on the occlusion site and hemodynamic status. Jet-like appearance is rarely shown in the petro-cavernous segment of the ICA or the origin of the BAs. Therefore, jet-like appearance is not an appropriate marker for predicting ICAS-O in these areas. Finally, a larger sample size and multicenter study are required to verify the predictive value of jet-like appearance for ICAS-O.

The present study proposed jet-like appearance in angiogram as an image marker for ICAS-O, with relatively high sensitivity and specificity. This could help operators predict underlying intracranial atherosclerotic stenosis in a timely manner and choose the best intervention strategy during thrombectomy.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Sir Run Run Shaw Hospital Ethics Committee School of Medicine, Zhejiang University. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

JZ and XJ proposed the concept and designed the study. XJ, YC, and XZ performed data collection and image analysis. FS and XJ performed statistical analysis. XJ and JZ drafted the paper, and JZ approved the final paper for publication. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.