Brain Hemorrhages 1 (2020) 59–64

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Brain Hemorrhages
CHINESE ROOTS
GLOBAL IMPACT
journal homepage: www.keaipublishing.com/en/journals/brain-hemorrhages/

Predictors of risk of intracerebral hemorrhage after intracranial artery

intervention in intracranial atherosclerotic stenosis patients
Liang Liu a,c, Jie Li b,c, Qing-Wu Yang b,⇑
a
Department of Neurology, The General Hospital of Northern Theater Command, Shenyang, Liaoning, China
b
Department of Neurology, Xinqiao Hospital, Army Medical University, Chongqing 400037, China

a r t i c l e i n f o a b s t r a c t

Article history: To investigate the relationship between clinical characters of intracranial atherosclerotic stenosis
Received 25 December 2019 patients and occurrence of cerebral hemorrhage after intracranial artery intervention. Clinical data of
Received in revised form 29 January 2020 total 501 patients who underwent endovascular therapy for ischemic stroke or transient ischemic attack
Accepted 29 January 2020
were retrospectively reviewed. Median (interquartile range, IQR) of the American Society of
Available online 15 February 2020
Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral
score was higher in intracerebral hemorrhage (ICH) group (P < 0.001). Cerebral blood flow (CBF) reducing,
Keywords:
cerebral blood volume (CBV) reducing, time to peak (TTP) delaying and mean transit time (MTT) delaying
Intracranial atherosclerotic stenosis
Intracranial artery stenting
in the lesion side comparing the contralateral side were higher in ICH group (P = 0.018, P = 0.046,
Complication P = 0.012, P = 0.038). ASITN/SIR  2, CBF reducing  40%, CBV reducing  30%, TTP delaying  2 s,
Cerebral hemorrhage MTT delaying  1 s, infarction volume  20 mL were probably the independent predictors of ICH follow-
Risk factor ing endovascular therapy.
Ó 2020 Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open
access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction we hypothesized that there might be some predictable factors in

At present, the prevention and treatment of cerebral hemor-
rhage after intracranial stent implantation mainly focus on inter-
ventional operation and postoperative management. Such as the
careful operation of the surgeon during the operation and postop-
erative blood pressure control could prevent the hyperperfusion
syndrome efficiently. After the interventional operation, the spe-
cial CT signs of the skull were obtained immediately to achieve
early detection, early identification and early treatment. And then
reduce the rate of cerebral hemorrhage complications to improve
surgical outcomes and reduce the serious consequences of compli-
cations. Thus, for intracranial atherosclerotic stenosis (ICAS)
patients before intracranial stent implantation, whether there are
relevant predictors can predict the risk of postoperative intracere-
bral hemorrhage which should be explored. It has been reported
that after endovascular therapy including thrombolysis and
thrombectomy in patients with acute ischemic stroke or transient
ischemic attack, there are independent risk factors that can predict
the occurrence of postoperative cerebral hemorrhage.1 Therefore,
⇑ Corresponding author at: Department of Neurology, Xinqiao Hospital, Army
Medical University, No. 183, Xinqiao Main Street, Shapingba District, Chongqing
400037, China.
E-mail address: yangqwmlys@163.com (Q.-W. Yang).
c
Liang Liu and Jie Li contributed equally to this work.
ICAS patients were associated with intracranial hemorrhage com-
plications after endovascular therapy.
2. Materials and methods
2.1. Subjects
This study was approved by the Ethics Committee of Xinqiao
Hospital, Army Military Medical University (Third Military Medical
University, Chongqing, China) (No. XQREC2012014H). All experi-
mental methods were carried out in accordance with the approved
guidelines. A total of 501 patients who received intravascular treat-
ment for ischemic stroke or TIA at Xinqiao hospital affiliated to the
Military Medical University (Third Military Medical University)
from June 2012 to April 2017 were collected. Inclusion criteria:
age 18–85; Symptomatic ICAS, TIA or ischemic stroke caused by
hypoperfusion of responsible blood vessels to the brain region over
3 weeks of onset; Digital subtraction angiography (DSA) was used
to measure symptomatic intracranial disease using normal distal
vessels as a reference; The middle cerebral artery, the intracranial
segment of the vertebral artery and the basilar artery were respon-
sible vessels, with a stenosis degree of 70%–100%; The hemody-
namic lesion in the responsible artery area was examined by
imaging within 2 weeks before surgery. At least one risk factor

https://doi.org/10.1016/j.hest.2020.01.005
2589-238X/Ó 2020 Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
60 L. Liu et al. / Brain Hemorrhages 1 (2020) 59–64
for atherosclerosis (high blood pressure, diabetes, hyperlipidemia,
smoking, etc.); the patient or immediate family member signs
the operation informed consent. These images were analyzed
intensively by three experienced doctors and agreed upon through
discussion when there was disagreement. Exclusion criteria: Non-
atherosclerotic stenosis; Stroke symptoms not due to thromboem-
bolism or hemodynamic changes; Intracranial hemorrhage
occurred within 6 weeks; Patients with potential cardiac embolism
sources; Complicated with intracranial tumors, aneurysms, cere-
bral arteriovenous malformations; Internal carotid artery extracra-
nial segment or vertebral artery tandem lesion, vascular stenosis
degree  50%; Contraindications of heparin, aspirin, clopidogrel,
anesthesia, and contrast agents; Platelet count < 100,000; The
international normalized ratio (INR) > 1.5 (irreversible) and uncor-
rectable bleeding quality; Life expectancy is less than 1 year.
2.2. Preoperative evaluation and medication
Ischemic stroke was identified by magnetic resonance diffusion
weighted sequence (DWI) according to the guidelines for diagnosis
and treatment of ischemic stroke. Due to possible vascular etiol-
ogy, the patient presented sudden focal brain or optic nerve dam-
age with a duration of less than 24 h. No abnormal images were
found in MRI, and the patient was diagnosed as TIA. During hospi-
talization, DSA or CT angiography (CTA) and CT perfusion imaging
(CTP) were performed to assess the degree of ischemia of anterior
or posterior intracranial circulation and intracranial circulation
reserve. Three to five days before stenting, all patients received
standard drug therapy, aspirin (100 mg/d) and clopidogrel
(75 mg/d). If emergency surgery is required, a loading dose of
300 mg clopidogrel and 300 mg aspirin can be taken. Aspirin
(100 mg/d) and clopidogrel (75 mg/d) were continued for 90 days
after surgery. At the same time, anticoagulant therapy (enoxaparin,
40 mg/12 h) was continued 3–5 days after stenting. In patients
with hyperlipidemia, low density lipoproteincholesterol (LDL-C)
was maintained below 70 mg/dL (1.81 mmol/L) or reduced LDL
level by 50%, while stabilizing plaque and reducing inflammatory
response. Patients with new cerebral infarction and massive cere-
bral infarction need at least 3 weeks to 1 month of medication
before stenting.
2.3. Stent implantation
The surgery was performed by 3 experienced neurointerven-
tional surgeons, each with more than 100 cases of intracranial
stent implantation, and selected the most appropriate materials
according to their experience and relevant guidelines. For patients
with easy passage and Mori A lesions, Apollo balloon stent was
selected. If the patient’s vascular path is tortuous, Mori C lesion
or the diameter difference between proximal and distal lesions is
large, the Gateway balloon plus Wingspanstentsystem (Stryker,
Maple Grove, MN) is used for such patients. To avoid head move-
ment, all operations were performed under general anesthesia. At
the beginning of the operation, 75 mg/kg of heparin was injected
intravenously, and half of the dose was given after 1 h. The femoral
artery was punctured by Seldinger method and the 6F/8F artery
sheath was placed. The 6F guide tube (Cordis Corporation, Miami,
FL) was placed into the C2 or V1 segments of the internal carotid
artery, the microguide wire was placed at the distal end of the
responsible vessel, and the microcatheter was then exchanged.
The Gateway balloon was ballooned through the stenosis segment,
the balloon was removed, the Wingspan stent was placed in the
stenosis segment of the responsible vessel, and the stent was
released after angiography confirmed that the placement was
accurate. Or the Apollo stent could be directly placed in the steno-
sis segment of the responsible vessel, and the stent could be
released after angiography confirmed accurate placement. Angiog-
raphy showed a significant improvement in stenosis after stent
release, and the stent delivery system was removed. During the
whole operation, the amount of iodoxacol (320 mgI/mL) was
150–300 mL. Intracranial angiography can be repeated for many
times during the 15–30 min postoperative observation, and the
operation is completed if no abnormal conditions are confirmed.
Head CT examination should be performed immediately 30 min
after stent implantation. If necessary, multiple head CT examina-
tions can be performed within 24 h. Then the patient was sent to
ICU for close monitoring for 24 h. Systolic and diastolic blood pres-
sure should be controlled below 120 mmHg and 80mmhg. At the
same time, the National Institute of Health stroke scale (NIHSS)
score was observed on 1, 3 and 7 days after surgery.
2.4. Data collection and imaging examination
Data collection and imaging examination (1) clinical data: age,
gender, smoking history, previous history (hypertension, diabetes,
hyperlipidemia, atrial fibrillation), previous use of anticoagulant
and antiplatelet drugs, admission NIHSS score, platelet count, LDL
value, INR value, blood glucose value, preoperative degree of vas-
cular stenosis. (2) CT parameters: (lightspeed-16, General Electric
Company, USA) Iamges: 1–28, CTDlvol: 40.46 mGy, DLP:
566.46 mGy/cm, Dose Eff: 97.40%, Scan Type: Axial, Desired KV:
120, Manual mA: 220, Thickness mm: 5.0, Interval mm: 20, DFOV
cm: 25.0, Window Width: 90 Hu, Window Level: 40 Hu. (3) dw-mri
parameters :(GE Signa EXEXITE HDxt 3.0 t) (repeat time TR/ corre-
sponding time te10000/70.4 ms, field of vision 22 cm  22 cm,
matrix size 128  256, layer thickness 2 mm, interlayer thickness
1.2 mm). According to the references, the calculation formula of
infarct volume = 0.5  a  b  c (a is the maximum longitudinal
diameter, b is the maximum transverse diameter, and c is the num-
ber of layers).2 (4) CTP parameter :(detector width 16 cm, thickness
0.5 mm; 56.0 mGy; DLP 896.3,kV 80, mA 300, FOV 220  220) CTP
can quantify and effectively reflect the change of blood perfusion in
local brain tissue, and can accurately compare the region of inter-
est (ROI) of the lesion with the blood perfusion in normal brain tis-
sue on the other side.3 Regional cerebral blood flow (rCBF): the
volume of blood that flows through the vascular structure of brain
tissue in a given unit of time. Regional cerebral blood volume
(rCBV): blood volume present in the vascular structure of a certain
amount of brain tissue. Represents the blood vessel bed volume of
capillaries and large blood vessels in ROI, reflecting the dilatation
of local blood vessels. It is related to the compensation degree of
collateral circulation. Regional mean transit time (rMTT): when
the blood flows through the vascular structure, including the blood
flow from the arteries to the capillaries and finally to the veins, the
passage time of the blood flow is also very different due to the dif-
ferent paths, so the mean transit time is used. So MTT is the time it
takes for contrast agents to pass through capillaries (the time it
takes for blood to flow from arteries to veins). Time to peak
(TTP): refers to the time from the beginning of injection of contrast
agent to the peak concentration.3 For patients with anterior circu-
lation lesions who underwent MCA stent implantation, the same
ROI on the left and right sides of the same layer of cerebral infarc-
tion lesion was selected for measurement comparison and the dif-
ference between the two sides was calculated. Where, the
calculation formulas of CBF and CBV = (lesion side - healthy side)/
healthy side  100%; the calculation formula of TTP and MTT = le-
sion side - healthy side.4 (5) classification of collateral circulation:
collateral circulation is one of the compensatory mechanisms of
cerebral circulation, which means that when the cerebral artery
supplying blood appears severe stenosis or occlusion due to vari-
ous reasons, the blood flow can reach the brain tissue in the
ischemic area through other blood vessels, so that the brain tissue
 L. Liu et al. / Brain Hemorrhages 1 (2020) 59–64 61

in the ischemic area can get different degrees of perfusion compen-
sation.5 According to the literature, there are three compensatory
pathways for the collateral circulation of cerebral arteries, namely:
the primary collateral circulation is compensated by the blood flow
of the circle of Willis; The secondary collateral circulation is com-
pensated by the blood flow of the ophthalmic artery, the anasto-
motic branch of the pia mater branch and the anastomotic
branch between the two branches. The tertiary collateral circula-
tion is compensated by the blood flow of neovascularization.5
ASITN/SIR collateral circulation grading evaluation system: grade
0, no collateral visible in ischemic area; Level 1, slow collateral
blood flow around the ischemic area. Grade 2, fast collateral blood
flow around the ischemic area, functional defect in the ischemic
area; at grade 3, the collateral blood flow was slow, but the venous
ischemic bed blood flow was complete after angiography. At grade
4, complete and rapid collateral blood flow is generated through
reverse perfusion in the entire ischemic area.6 Currently, digital
subtraction angiography (DSA) is considered as the gold standard
for evaluating collateral circulation.6 DSA examination can clearly
show the shape of each cerebrovascular, including arteries, veins
and capillaries. Therefore, DSA can accurately discover the stenosis
or occlusion of cerebral artery, observe the anatomical structure of
various collateral circulation and the scope of compensatory blood
supply. Compared with other examination methods, DSA also has
obvious advantages in judging the opening degree of pia mater col-
lateral. In this study, DSA examination was used to observe the col-
lateral circulation of patients, and all patients were graded
according to the ASITN/SIR collateral circulation grading evaluation
system.
2.5. Statistical analyses
Statistical analyses were carried out using SPSS 17.0 software
(SPSS, Inc., Chicago, IL, USA). For continuous variables,
Kolmogorov-Smimov test is used to test whether they conform
to normal distribution. Continuous variables consistent with nor-
mal distribution were expressed as (mean ± standard deviation),
and Student’s t test was used to test whether there was statistical
difference between the two groups. Continuous variables that did
not conform to normal distribution were expressed as median
(quartile), and Mann–Whitney U test was used to test whether
there were statistical differences between the two groups. The
classified variables were expressed as frequency (percentage),
and the differences were compared by Pearson Chi-Square test or
Fisher’s exact test. With the occurrence of cerebral hemorrhage
as the dependent variable and the risk factor as the independent
variable, multivariate binary Logistic regression analysis was con-
ducted for the independent variable P < 0.05, and P < 0.05 was con-
sidered as the independent risk factor for cerebral hemorrhage.
3. Results
3.1. Characteristics of study population
Among the 501 patients, CT were conducted immediately after
surgery and the results of CT scan indicated cerebral hemorrhage
in 19 patients, which were namely cerebral hemorrhage group,
among which 17 patients (89.5%) received middle cerebral artery
(MCA) stent placement, 1 patient (5.3%) received basilar artery
(BA) stent placement, and 1 patient (5.3%) received V4 stent place-
ment. The remaining 482 patients were assigned into the control
group. There were significant differences in the history of hyper-
tension and smoking between the cerebral hemorrhage group
and the control group (P < 0.05), while there were no significant
differences between the other data and the control group
(P > 0.05), as shown in Table 1.
3.2. Collateral circulation classification
In this study, ASITN/SIR classification was as follows (Fig. 1), in
the cerebral hemorrhage group, there were 5 cases of grade 0, 12
cases of grade 1, and 2 cases of grade 2. In the control group, there
were 28 cases of grade 0, 67 cases of grade 1, 205 cases of grade 2,
166 cases of grade 3, and 16 cases of grade 4. ASITN/SIR in the cere-
bral hemorrhage group was 1 (0–2), and ASITN/SIR in the control
group was 2 (0–4). There was a significant difference between
the two groups (P < 0.001).
3.3. CTP characteristics
The CTP assessment of perfusion is only applicable to patients
undergoing anterior circulation, i.e., MCA stenting. In the cerebral

Table 1
Demographic characteristics of Cerebral hemorrhage group and Control group.

Variables Cerebral hemorrhage group Control group P value

Demographic characteristics N = 19 N = 482
Age, mean (SD) 63.5 (11.2) 65.2 (13.6) 0.591
Male, number (%) 17 (89.5) 350 (72.6) 0.103
NIHSS score [M(IQR)] 4 (0–12) 2 (0–16) 0.262
Platelets (SD) 186.53 (46.33) 192.38 (55.52) 0.651
LDL (mmol/L, SD) 2.72 (0.84) 2.51 (0.83) 0.275
INR [M(IQR)] 0.94 (0.74–1.03) 0.89 (0.73–1.61) 0.533
Blood glucose (mmol/L, SD) 5.83 (2.91) 5.92 (2.68) 0.889
Infarct volume [mL, M(IQR)] 15.9 (0–33.5) 9.55 (0–40.5) 0.011
Degree of stenosis before treatment (%, SD) 87.37 (10.98) 83.31 (8.84) 0.052
Medical history number (%)
Smoking 15 (78.9) 245 (50.8) 0.016
Hypertension 18 (94.7) 302 (62.7) 0.004
Hyperlipemia 13 (68.4) 238 (49.4) 0.057
Diabetes 9 (47.4) 179 (37.1) 0.366
Atrial fibrillation 2 (10.5) 21 (4.4) 0.483
Previous use of antiplatelet drugs 6 (31.8) 86 (17.8) 0.224
Previous use of anticoagulant drugs 2 (10.5) 19 (3.9) 0.412
Stents position (%)
MCA 17 (89.50) 359 (74.5) 0.392
BA 1 (5.3) 68 (14.1) 0.392
V4 1 (5.3) 45 (9.3) 0.392
62 L. Liu et al. / Brain Hemorrhages 1 (2020) 59–64

Fig. 1. ASITN/SIR collateral circulation classification of Cerebral hemorrhage group and Control group.

hemorrhage group, the CBF in the infarcted side was 35.29% lower
Table 3
than that in the contralateral side, and in the control group, the CBF Multivariate analysis of predictors of cerebral hemorrhage after interventional
in the infarcted side was 18.52% lower than that in the contralat- therapy.
eral side (P = 0.018). In the cerebral hemorrhage group, the CBV
Risk factors Increment/category OR (95% CI) P value
of the infarcted side was 33.85% lower than that of the contralat-
eral side, and in the control group, the CBV of the infarcted side Hypertension v.s. No hypertension 1.22 (0.83–1.36) 0.742
Smoking v.s. No smoking 1.13 (0.88–1.35) 0.758
was 23.07% lower than that of the contralateral side (P = 0.046).
Infarct volume  20 mL v.s. < 20 mL 1.70 (1.25–2.69) 0.039
In the cerebral hemorrhage group, the TTP of the infarcted side ASITN/SIR  2 v.s. >3 1.97 (1.36–2.81) 0.013
was 2.1 s longer than that of the contralateral side, while in the CBV reduction  30% v.s. < 30% 2.27 (1.24–4.14) 0.008
control group, the TTP of the infarcted side was 1.3 s longer than CBF reduction  30% v.s. < 30% 1.41 (1.07–2.96) 0.083
CBF reduction  40% v.s. < 30% 2.11 (1.27–3.05) 0.027
that of the contralateral side (P = 0.012). Compared with the con-
TTP extension  2 s v.s. < 2 2.07 (1.24–3.46) 0.006
tralateral group, the MTT on the infarct side in the cerebral hemor- MTT extension  1 s v.s. < 1 1.70 (1.02–2.78) 0.039
rhage group was prolonged by 1.7 s, while the MTT on the infarct
side in the control group was prolonged by 1.0 s (P = 0.038), as
shown in Table 2.
endothelial cells of the vascular wall also cause necrosis due to
ischemia and hypoxia, leading to endothelium damage.7 Then,
3.4. Multivariate analysis of predictors of cerebral hemorrhage the larger the infarct size, the more severe the cerebral edema,
the more severe the endothelial cell damage in the capillary wall,
With the occurrence of cerebral hemorrhage as the dependent and the more severe the damage of the blood–brain barrier that
variable and the risk factor as the independent variable, multivari- damages the brain tissue. At the same time, there are reports that
ate binary Logistic regression analysis was conducted for the inde- the infarct size is positively correlated with hemorrhagic transfor-
pendent variable P < 0.05, and P < 0.05 was considered as the mation (HT).8 Therefore, in patients with larger cerebral infarction,
independent risk factor for cerebral hemorrhage. ASITN/SIR  2, the blood–brain barrier is more severely damaged, and the
CBF  40%, CBV  -30%, TTP  2 s, MTT  1 s, and infarct endothelial cell and vascular autoregulation function is more
volume  20 mL are likely to be independent risk factors for post- severely damaged in the lesion, and when the intracranial vascular
operative hemorrhagic stroke after intracranial arterial stent stent is placed, the vascular stenosis is relieved and the blood flow
implantation, as shown in Table 3. is re-exposed. Thus, the possibility of patient occurs cerebral hem-
orrhage increased significantly. In this study, the infarct volume
4. Discussion was 15.9 mL (0–33.5) in the cerebral hemorrhage group and
9.55 mL (0–40.5) in the control group. The difference between
Whether there is a correlation between the occurrence of surgi- the two groups was statistically significant (P = 0.011). In multi-
cally related cerebral hemorrhage after intracranial arterial stent variate regression analysis, infarct volume  20 mL was associated
implantation and the characteristic factors of ICAS patients, and with cerebral hemorrhage after intracranial stent placement.
whether there is a predictable factor, are the main questions dis- CT perfusion imaging was used to measure the perfusion of
cussed in this study. local brain tissue, and the hemodynamic changes in the lesion area
When cerebral infarction occurred due to stenosis or occlusion, and the contralateral normal area were compared. It is of great sig-
the endothelial cells of the vessel wall are degenerated and necro- nificance for the surgical evaluation of patients with cerebral vas-
tic due to ischemia and hypoxia, and the vascular permeability is cular stenosis before interventional therapy.6 At present, CT
abnormally increased after endothelial cell necrosis, followed by perfusion imaging is mostly used for the diagnosis of anterior cir-
capillary rupture and erythrocyte infiltration. The vascular culation ischemia, but it is rarely used in the study of posterior cir-
autoregulation function is impaired, if a large area of cerebral is culation. The commonly used indicators in clinical practice are CBF,
infarcted which can cause severe cerebral edema, then the capillar- CBV, MTT and TTP. The CBF response is the blood volume that flows
ies of the tissue surrounding the infarct are compressed, and the through a certain amount of brain tissue vascular structure per

Table 2
Comparison of the CTP between Cerebral hemorrhage group and Control group.

Variables Cerebral hemorrhage group Control group P value

Number of patients N = 17 N = 359
CBF/[mL/(min
100 g), M(IQR)] 35.29% (14.29%–84.62%) 18.52% (4.20%–77.78%) 0.018
CBV/[mL/100 g, M(IQR)] –33.85% (14.29%–73.99%) –23.07% (4.07%–65.70%) 0.046
TTP/[s, M(IQR)] 2.1 (0.6–6.4) 1.3 (0.1–3.0) 0.012
MTT/[s, M(IQR)] 1.7 (0.3–3.6) 1.0 (0.1–3.6) 0.038
 L. Liu et al. / Brain Hemorrhages 1 (2020) 59–64
unit time, and the assessment of local brain tissue perfusion is
more sensitive than CBV. MTT mainly reflects the time when the
contrast agent passes through the capillaries (the time when blood
flows from the artery to the vein). The larger the value, the worse
the microcirculation. TTP refers to the time from the start of injec-
tion of contrast agent to the peak concentration of contrast agent,
and the more obvious TTP prolongation, the more serious the
hemodynamic damage of the detected brain and the slower blood
flow in blood vessels.9–11 The Bayliss effect means that when the
cerebral blood perfusion pressure fluctuates within a certain range,
the body can maintain the relative dynamic stability of cerebral
blood flow through the compensatory expansion or contraction
of small arteries and capillary smooth muscle.5 Therefore, under
normal condition, the cerebral blood vessels will maintain the nor-
mal stability of cerebral blood flow through the Bayliss effect. This
ability is called cerebral circulation reserve. However, when the
patient’s cerebral blood perfusion declines beyond the normal
cerebral circulation reserve, cerebral infarction or TIA will occur,
and CTP will change accordingly. MTT and TTP are prolonged on
the lesion side, CBF is significantly decreased, CBV is decreased
or slightly decreased. In this study, the CBF on the infarct side of
the cerebral hemorrhage group decreased by 35.29% compared
with the contralateral side, and the infarction side CBF of the con-
trol group decreased by 18.52%. In the cerebral hemorrhage group,
the CBV of the infarct side decreased by 33.85 compared with the
contralateral side, and the infarct side CBV of the control group
decreased by 23.07%. The TTP in the infarct side of the cerebral
hemorrhage group was longer than the contralateral side by
2.1 s, and the infarct TTP in the control group was extended by
1.3 s compared with the contralateral side. The MTT in the
infarcted side of the cerebral hemorrhage group was 1.7 s longer
than the contralateral side. In the control group, the MTT of the
infarct side was extended by 1.0 s compared with the contralateral
side. When the patient’s responsible vessel is severely stenotic or
occluded, the blood flow supplied will be severely limited. In order
to maintain the cerebral blood volume at normal levels, the blood
vessels will be dilated as much as possible. When the blood vessels
expand to the limit, the autoregulation of the blood vessels is
impaired, and cerebral blood flow can only be directly dependent
on systemic blood pressure. Therefore, after the intracranial vascu-
lar stent placement, the stenosis is relieved and the blood vessels
are recanalized. Besides, a large amount of blood is poured into
the distal end of the blood vessel, and the rapid increase of cerebral
blood flow and the damage of the blood vessel autoregulation
function are easy to cause blood–brain barrier destruction and
cerebral hemorrhage. Therefore, in this study, the cerebral perfu-
sion of the lesion side of the hemorrhage group is larger than that
of the normal contralateral cerebral perfusion. Therefore, after the
intracranial stent placement, the vascular stenosis is relieved and
the blood flow is recanalized. Then the cerebral perfusion changes
are more likely to occur intracerebral hemorrhage. In this study,
multivariate binary logistic regression analysis showed that CBF
decreased  -40%, CBV decreased  -30%, TTP prolonged  2 s,
MTT prolonged  1 s was associated with cerebral hemorrhage
after intracranial stenting.
Both collateral circulation and cerebral perfusion CT reflect
cerebral blood perfusion. CTP reflects the blood–brain perfusion
of regional brain tissue and is more commonly used in the evalua-
tion of anterior circulation perfusion. The collateral circulation of
the brain reflects the cerebral circulation reserve capacity of the
whole brain, including the anterior and posterior circulation. When
a hemodynamic disorder caused by cerebral vascular stenosis or
occlusion occurs, it causes a decrease in cerebral perfusion pres-
sure. In addition to the degree of vascular stenosis, the reduction
of cerebral perfusion pressure depends on two other aspects, one
is the condition of the medial branch of the brain, and the other
63
is the reserve capacity of the cerebral blood vessels.12 If the medial
branch of the brain is sufficiently abundant and the cerebral vascu-
lar reserve is strong enough, even a severe stenosis or occlusion of
the cerebral vessels will not cause a significant decrease in cerebral
perfusion pressure. The cerebral collateral circulation is one of the
mechanisms of cerebral circulation compensation. When the blood
supply cerebral artery is severely stenosis or occlusion due to var-
ious reasons, the blood flow can reach the ischemic area of the
brain tissue through other blood vessels, thus the ischemic brain
tissue is compensated for varying degrees of perfusion.13 The Willis
circle is the most important collateral circulation pathway in
intracranial blood vessels, usually acting in the early stage of ische-
mia and acting as primary collateral compensatory. The Willis cir-
cle connects the major aorta in the skull, allowing the left, right
anterior circulation and corresponding posterior circulation of
blood flow. Usually, the anterior and posterior communicating
arteries in the intracranial vessels are not open, but when there
is severe stenosis or occlusion of the intracranial arteries, the regio-
nal cerebral blood flow is significantly reduced and the perfusion
pressure is decreased in the part of the anterior communicating
artery, and the anterior communicating artery and/or the traffic
artery may be open to provide compensated blood flow to the
affected area, thereby reducing or alleviating ischemic symptoms.
When the compensation of the Willis circle does not meet the cere-
bral perfusion requirements, the secondary collateral circulation
compensation pathway will work. Secondary collateral circulation
compensation has two pathways, including the ophthalmic artery
and the pia mater artery. If the internal carotid artery shows
chronic severe stenosis or occlusion before the ophthalmic artery
is emitted, the blood flow of the external carotid artery will be sup-
plied to the internal carotid artery through the ophthalmary artery,
so the ophthalmic artery mainly communicates with the internal
carotid artery system and the external carotid artery system.
Another route of secondary collateral circulation compensation is
the pial-macular anastomosis, in which the distal end of the cere-
bral cortical branch forms a broad network of vascular networks in
the pia mater. When the secondary compensation still cannot meet
the cerebral perfusion supply demand, the new blood vessels
become the final collateral compensatory pathway, that is, the ter-
tiary collateral circulation compensation.13 At present, the collat-
eral circulation of the brain has become a hot topic. The clinical
significance of the collateral circulation is known as follows: pro-
longing the time window of endovascular treatment,13 predicting
the efficacy of endovascular treatment,14 reducing intravascular
Treatment of hemorrhagic transformation risk,15 predictors of arte-
rial thrombolysis and hemorrhage, 16 predicting clinical and imag-
ing outcomes in stroke patients,17 and changing stroke risk in
patients with intracranial stenosis.18
According to the ASINT/SIR collateral circulation grading evalu-
ation system, the collateral circulation can be divided into 0–4
grades: 0, no collaterals can be seen in the ischemic area; 1st grade,
there is slow collateral blood flow around the ischemic area; There
is rapid collateral blood flow around the ischemic area, and there is
functional defect in the ischemic area; grade 3, collateral blood
flow is slow, but venous ischemic blood flow is complete after
angiography; grade 4, the entire ischemic area exists Complete
and rapid collateral blood flow produced by reverse perfusion.6
Patients with poor collateral circulation are more likely to have
ischemic stroke or TIA when the cerebral vascular stenosis or
occlusion is severe. Meanwhile, patients with poor collateral circu-
lation after intracranial vascular stent placement, a large amount of
blood flow increased suddenly, and the cerebral blood vessels
damaged by the self-regulating mechanism could not contract
accordingly, resulting in hyperperfusion of the ipsilateral brain tis-
sue, which in turn induced cerebral hemorrhage.19 The median
ASITN/SIR was 1 (0–2) in the cerebral hemorrhage group, and the
64 L. Liu et al. / Brain Hemorrhages 1 (2020) 59–64
median ASITN/SIR was 2 (0–4) in the control group. There was a
significant difference between the two groups. The results of this
study validate the results of previous literature studies. The lower
the cerebral collateral circulation, the higher the risk of cerebral
hemorrhage after intracranial stent implantation, and vice versa.
In this study, multivariate regression analysis of ASITN/SIR  2
was associated with cerebral hemorrhage after intracranial
stenting.
In summary, the study found that hypertension, smoking his-
tory, infarct volume, CBV, CBF, MTT, TTP, ASITN/SIR in the postop-
erative cerebral hemorrhage group and the control group were
statistically significant, binary logistic Factor regression analysis
suggested that ASITN/SIR  2, CBF decreased by  40%, CBV
decreased by  30%, TTP prolonged  2 s, MTT prolonged  1 s,
infarct volume  20 mL are independent risk factors for patients
with intracranial stent implantation occurring intracerebral hem-
orrhagic. Although the occurrence of intracranial vascular
stenting-related complications is related to complex and compre-
hensive factors, it is possible to reduce and avoid the occurrence
of serious postoperative complications through the regulation of
these risk predictors. For example, strict screening of surgical
patients, repeated assessment of preoperative vascular stenosis
and cerebral perfusion, adaptation of preoperative high-
perfusion, reasonable timing of surgery, choice of surgical
approach, selection of step-by-step staging, postoperative blood
pressure monitoring and so on. It is expected to help patients, fam-
ilies and surgeons to fully evaluate and recognize the risk of sur-
gery, and ultimately avoid serious surgical complications, so that
patients can get more effective and safer treatment.
Intracranial stent implantation is a new and effective treatment
for prevention of the recurrence stroke in patients with severe
atherosclerotic stenosis, but the incidence of complications of
interventional treatment of intracranial artery stenosis is relatively
high and dangerous. Further research into the risks and benefits of
this treatment is needed to help doctors assess the safety of this
emerging treatment. This study is only a single center study, and
the sample is limited in the Chinese population. Therefore, the
above results have certain limitations and may not be applicable
to other ethnic groups. Thus, we look forward to further multi-
center, larger sample studies to confirm our findings.
Funding
This research project was supported by grants from the
National Natural Science Fund for Distinguished Young Scholars
(81525008).
Declaration of Competing Interest
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
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