Edited by: Thomas W. Leung, The Chinese University of Hong Kong, China
Reviewed by: Shreyas Gangadhara, University of Mississippi Medical Center, United States; Xinyi Leng, The Chinese University of Hong Kong, China
This article was submitted to Endovascular and Interventional Neurology, a section of the journal Frontiers in Neurology
†These authors have contributed equally to this work
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Stroke has now become the first most common and disabling disease in China, and intracranial artery stenosis or occlusion is one of the leading causes of ischemic stroke in Asian populations (
Given the high risk of recurrent stroke in patients with CIAO, endovascular angioplasty and stenting have been performed in clinical practice and some studies (
The study was performed according to the guidelines from the Helsinki Declaration, and it was approved by the institutional review board (IRB) of the hospital. Written informed consent was obtained from all patients or their legally authorized guardian. We retrospectively and consecutively collected patients who were diagnosed with CIAO, received endovascular recanalization, and underwent whole-brain CTP before and after the recanalization in our stroke center from June 2014 to June 2019. The data that support the findings of this study are available from the corresponding author upon reasonable request.
The included patients suffered a symptomatic CIAO in the intracranial ICA, middle cerebral artery (MCA), intracranial vertebral artery (VA), or basilar artery (BA). The symptoms included transient ischemic attack (TIA) and ischemic stroke within the past 90 days, which was attributable to hypoperfusion in the territory of the culprit arteries. Ischemic stroke referred to a new focal neurologic deficit lasting ≥24 h or lasting <24 h with new infarction on imaging, and TIA was defined as acute onset of a focal neurologic deficit lasting <24 h without new infarction on imaging. Hemodynamic impairment in the territory of the culprit artery was determined on imaging within 2 weeks before the procedure using any one of the following methods: (1) a cerebral blood flow (CBF) decrease of ≥30% when compared with the perfusion on the contralateral side for anterior circulation lesions or the anterior circulation territory for posterior circulation lesions on CTP; (2) an American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) Collateral Flow Grading System score of <3 on digital subtraction angiography (DSA) (
The imaging protocol includes whole-brain CTP before and after the endovascular recanalization. CTP studies were performed in the transverse plane by using a 256-slice axial CT scanner (GE Revolution CT) before and after the recanalization for all subjects. A 50-ml bolus of contrast media (Omnipaque, 350 mg I/ml; GE Healthcare, Shanghai, CN) was administered into an antecubital vein by using a power injector (Ulrich Injection System; Ulrich GMBH & CO. KG, Germany) with an injection rate of 5 ml/s. CT scanning was initiated 5 s after the start of the injection with the following acquisition parameters: 80 kV tube voltage, 150 mA, 5 mm slice thickness, 256 * 0.625 mm collimation, 0.5 s rotation time, 2.0 s cycle time, 25-cm field of view (FOV), 512 * 512 image matrix size, 32 slices. A total of 512 slices were obtained with a scan time of about 40 s and 160 mm scan length. Brain standard reconstruction was performed with the CT system. During the conduction of CTP, the mean arterial pressure of patients was generally maintained between 80 and 120 mmHg to avoid the impact of high or low blood pressure on CBF.
CTP source data were transferred from the clinical imaging database to a designated workstation (GE Workstation AW 4.7), and the whole-brain CTP images were reconstructed from source data for analysis. The software relies on the central volume principle to calculate perfusion parameters from the time–concentration curve. The mean transit time (MTT) was calculated by a closed-form deconvolution operation from the time–concentration curve and the arterial input function (AIF). The first artery to reach peak enhancement on the time–attenuation curve was selected as the AIF. The vein with the largest area under the time–attenuation curve was selected as the volume of fluid (VOF). The cerebral blood volume (CBV) was calculated from the areas under the time-concentration curves. The CBF was calculated according to the following equation: CBF = CBV/MTT. The time to peak (TTP) referred to the length of time for brain tissue to reach enhancement of peak density. Large vessels were automatically excluded via the brain perfusion software.
Two experienced neuroradiologists independently drew standardized elliptical regions of interest (ROIs) manually in the perforating artery territory (PAT) and cortical artery territory (CAT). For anterior circulation occlusion (ACO), PAT was selected in the basal ganglia, CAT was selected in the cortical middle cerebral artery territory, and mirror CAT was selected as reference area (
Schematic diagram of regions of interest (ROIs) in the region of perforating artery territory (PAT) and cortical artery territory (CAT) in anterior circulation
All the images of CTP were interpreted by two experienced neuroradiologists independently, and a CTP interpretation training program was performed for both of them to ensure the consistency of interpreting standard. The differences between their assessments were resolved by a third senior neuroradiologist (categorical data), or we took the average of their data (quantitative data) to reduce the impact of subjective factors.
The procedures were performed by experienced neurointerventionists. The operators were instructed to choose devices based on their experience and preference, as well as the conditions of individual patients. All patients were given a weight-based dose of 0.4–0.6 ml Fraxiparine (Sanofi Winthrop Industry) every 12 h subcutaneously for 3 days and monitored closely until discharge. All patients received aspirin (100 mg/day) and clopidogrel (75 mg/day) for more than 5 days before the operation. They were maintained on aspirin (100 mg/day) plus clopidogrel (75 mg/day) for 90 days after stenting. Other medical therapy included control of risk factors, such as blood pressure and low-density lipoprotein.
In stratified analysis, the patients were categorized into subgroups based on the occlusion sites, restenosis status, and time interval from revascularization to post-procedural CTP. Restenosis was defined as >70% stenosis within or immediately adjacent (within 5 mm) of the implanted stent compared with the diameter of reference vessels based on DSA or CT angiography source imaging. The short-term group was defined as those patients who underwent CTP within 7 days after the procedure, the mid-term group as CTP with a time interval from 7 days to 6 months, and the long-term group with a time interval of more than 6 months.
The statistical analysis was performed using a commercial statistical software package (SPSS for Windows, version 25.0, IBM-SPSS, Chicago, IL, US). The mean or median of CTP values on each ROI were calculated before and after the procedure. Normal distribution data were expressed as mean ± SD, while skew distribution data were expressed as median [interquartile range (IQR)], and categorical data were expressed as
From June 2014 to June 2019, among 76 patients with symptomatic CIAO who have received endovascular treatment, 20 patients (56.1 ± 7.0 years old) with pre- and post-procedural CTP were recruited, including 16 male patients (80.0%) and four female patients (20.0%). The occlusion sites included intracranial ICA (
Baseline clinical and endovascular treatment characteristics.
Male, |
16 (80%) |
Age, mean ± SD | 56.1 ± 7.0 |
BMI, median (IQR) | 24.1 (23.3–27.2) |
Risk factors | |
Hypertension, |
17 (85%) |
Diabetes mellitus, |
6 (30%) |
Hyperlipidemia, |
12 (60%) |
Coronary heart disease, |
2 (10%) |
Smoking, |
15 (75%) |
Occlusion sites, |
|
Intracranial ICA | 6 (30%) |
MCA | 7 (35%) |
Intracranial VA | 5 (25%) |
BA | 2 (10%) |
Length of the lesion (mm), median (IQR) | 13 (8.5–20.25) |
Baseline NIHSS, median (IQR) | 1 (0–2) |
Baseline mRS, median (IQR) | 1 (0–1) |
Time interval from symptoms onset to the procedure (days), median (IQR) | 60.5 (38.5–122.25) |
Time interval from documented occlusion to the procedure (days), median (IQR) | 19 (7.75–27.0) |
Time interval from pre-operative CTP to revascularization (days), median (IQR) | 3 (1–6) |
Time interval from revascularization to post-operative CTP (months), median (IQR) | 4.0 (0.2–23.7) |
The mean absolute CBF increased significantly after recanalization from 29.28 to 39.33 ml • 100 g−1 in PAT (
Comparison of pre- and post-operative CTP values in the regions of PAT and CAT.
CBF (ml·100 g−1·min−1) | 29.28 ± 11.71 | 39.88 ± 10.66 | <0.001 | 32.60 ± 11.06 | 47.84 ± 12.21 | <0.001 |
CBV (ml·100 g−1) | 2.57 (2.37–3.16) | 2.55 (2.21–2.93) | 0.073 | 3.50 ± 0.91 | 3.12 ± 0.61 | 0.024 |
MTT (s) | 6.73 (5.03–9.08) | 4.62 (3.31–5.78) | 0.001 | 7.85 (6.09–9.93) | 4.40 (3.61–5.70) | <0.001 |
TTP (s) | 12.51 (11.75–14.21) | 11.17 (10.33–12.81) | 0.010 | 14.06 ± 2.23 | 11.93 ± 2.44 | 0.002 |
rCBF | 0.52 ± 0.12 | 0.71 ± 0.19 | <0.001 | 0.59 ± 0.10 | 0.85 ± 0.20 | <0.001 |
rCBV | 0.87 ± 0.14 | 0.83 ± 0.12 | 0.305 | 1.09 ± 0.24 | 1.01 ± 0.19 | 0.034 |
rMTT | 1.66 (1.36–1.96) | 1.08 (0.99–1.36) | 0.002 | 1.85 (1.40–2.17) | 1.13 (0.94–1.51) | <0.001 |
rTTP | 1.20 (1.13–1.23) | 1.06 (1.01–1.21) | 0.001 | 1.31 ± 0.10 | 1.14 ± 0.13 | <0.001 |
In subgroup analysis, the rCBF increase retained statistically significant in patients with different occlusion sites, at different time intervals, and in patients without restenosis (
Stratified analysis of pre- and postoperative comparison of rCBF in the regions of PAT and CAT.
Occlusion sites | ACO ( |
0.54 ± 0.13 | 0.70 ± 0.19 | 0.001 | 0.59 ± 0.10 | 0.84 ± 0.23 | 0.001 |
PCO ( |
0.48 ± 0.11 | 0.73 ± 0.20 | 0.028 | 0.59 ± 0.09 | 0.88 ± 0.15 | 0.006 | |
Time interval | Short-term ( |
0.55 ± 0.06 | 0.85 ± 0.18 | 0.024 | 0.63 ± 0.10 | 1.01 ± 0.13 | 0.006 |
Midterm ( |
0.59 ± 0.14 | 0.72 ± 0.18 | 0.049 | 0.57 ± 0.12 | 0.84 ± 0.27 | 0.011 | |
Long-term ( |
0.44 ± 0.11 | 0.60 ± 0.14 | 0.016 | 0.58 ± 0.08 | 0.74 ± 0.10 | 0.014 | |
Restenosis | Yes ( |
0.50 ± 0.13 | 0.56 ± 0.16 | 0.161 | 0.57 ± 0.10 | 0.71 ± 0.23 | 0.084 |
No ( |
0.53 ± 0.12 | 0.79 ± 0.15 | <0.001 | 0.60 ± 0.10 | 0.93 ± 0.14 | <0.001 |
Comparison of the proportion of relative cerebral blood flow change (rCBFc%) in patients with different occlusion sites, at different time intervals, and restenosis status. *Represents extreme value (more than three box lengths from either end of the box), and circles represent outliers (between one and a half and three box lengths from either end of the box).
To the best of our knowledge, this is the first conducted study focusing on post-procedural hemodynamic changes over time in patients with CIAO based on CTP. CTP is a readily accessible and reliable method for the evaluation of cerebral hemodynamic characteristics and has been widely used in the cerebral hemodynamic evaluation of stenotic or occlusive cerebrovascular disease in clinical practice (
The results indicated that in patients with CIAO who had received endovascular recanalization, post-procedural CBF increased significantly in both PAT and CAT regions. The stratified analysis demonstrated that the CBF increase retained statistically significant in patients with different occlusion sites, at different time intervals, and in patients without restenosis. This indicated that successful recanalization might increase CBF and improve cerebral hemodynamics in patients with CIAO. Similar changes had been found in patients with chronic carotid artery occlusion after interventional or surgical recanalization in previous studies (
In the present study, the CBF increase retained relatively stable in the long term after successful recanalization, although the mid-term tendency of decrease was observed. The short-term CBF increase may be attributed to the hyperperfusion phenomenon after successful recanalization. The CBF values in the midterm and long term were lower than that in the short term, and this reflected the real and meaningful CBF changes after the recanalization, and it can keep relatively stable over time, which suggested that the long-term efficacy of endovascular treatment for CIAO was acceptable.
For patients with restenosis, the post-procedural CBF also showed a tendency to increase without statistical difference compared with pre-procedural CBF, but the rCBFc% was significantly lower than that in patients without restenosis (18.5 vs. 37.3%,
The rCBFc% in patients with posterior circulation occlusion was relatively higher than that in patients with anterior circulation occlusion (50.4 vs. 33.4%,
In the present study, most of the patients had a good outcome during the follow-up period, and recurrent post-operative stroke occurred only in two patients. Therefore, we did not evaluate whether improved hemodynamics was associated with good outcomes or reduced risk of recurrent stroke. Future studies with larger sample sizes and longer follow-up intervals are needed to confirm this relationship.
Potential limitations of this study should be mentioned. First, the sample size was small in this study, and the patients were enrolled from a single center, so potential selection bias may be inevitable. Second, ROIs in this study were drawn manually, and only parts of the PAT or CAT were evaluated. It is practically challenging to draw ROIs in a completely consistent area before and after the recanalization. However, we had tried our best to draw almost the same ROIs in the same areas before and after the recanalization. Third, the retrospective nature of the study necessitates further studies to confirm our conclusions.
In patients with symptomatic CIAO, the CBF may increase and be relatively stable over time after successful recanalization except for restenosis.
The data that support the findings of this study are available from the corresponding author upon reasonable request.
The study was performed according to the guidelines from the Helsinki Declaration, and it was approved by the IRB of the hospital. Written informed consent was obtained from all patients or their legally authorized guardian.
KK and BY contributed to the conception/design of the study, the acquisition, analysis, and interpretation of data, drafting of the manuscript, and final approval of the version to be published. XG, WG, and GM were responsible for the acquisition of data and final approval of the version to be published. XC was responsible for critical revision of the manuscript and final approval of the version to be published. NM, XZ, and ZM were responsible for the conception/design of the study, revision of the work, final approval of the version to be published, and agreement to be accountable for all aspects of the work.
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. The handling editor declared a past co-authorship with one of the authors XZ.
We thank all of the patients and health care providers who participated in the present study.