Quantitative Assessment of Changes in Hemodynamics After Obliteration of Large Intracranial Carotid Aneurysms Using Computational Fluid Dynamics

Abstract

Background: It was speculated that the alteration of the geometry of the artery might lead to hemodynamic changes of distal arteries. This study was to investigate the hemodynamic changes of distal arterial trees, and to identify the factors accounting for hyperperfusion after the obliteration of large intracranial aneurysms.
Methods: We retrospectively reviewed data of 12 patients with intracranial carotid aneurysms. Parametric models with intracranial carotid aneurysm were created. Patient-specific geometries were generated by three-dimensional rotational angiography. To mimic the arterial geometries after complete obliteration of the aneurysms, the aneurysms were virtually removed. The Navier–Stokes equations were solved using ANSYS CFX 14. The average wall shear stress, pressure and flow velocity were measured.
Results: Pressure ratio values were significantly higher in A1 segments, M1 segments, and M2 + M3 segments after obliteration of the aneurysms (p = 0.048 in A1 segments, p = 0.017 in M1 segments, p = 0.001 in M2 + M3 segments). Velocity ratio values were significantly higher in M1 segments and M2 + M3 segments after obliteration of the aneurysms (p = 0.047 in M1 segments, p = 0.046 in M2 + M3 segments). The percentage of pressure ratio increase after obliteration of aneurysms was significantly correlated with aneurysmal angle (r = 0.739, p = 0.006 for M2 + M3).
Conclusions: The pressure and flow velocity of distal arterial trees became higher after obliteration of aneurysms. The angle between the aneurysm and the parent artery was the factor accounting for pressure increase after treatment.

Full text

ORIGINAL RESEARCH
published: 29 April 2021
doi: 10.3389/fneur.2021.632066
Frontiers in Neurology | www.frontiersin.org 1April 2021 | Volume 12 | Article 632066
Edited by:
Osama O. Zaidat,
Northeast Ohio Medical University,
United States
Reviewed by:
Jan Jack Gouda,
Wright State University, United States
Ali Alaraj,
University of Illinois at Chicago,
United States
*Correspondence:
Yongsheng Liu
liuyongsheng_dl@163.com
Feng Wang
1691301142@qq.com
†These authors have contributed
equally to this work
Specialty section:
This article was submitted to
Endovascular and Interventional
Neurology,
a section of the journal
Frontiers in Neurology
Received: 22 November 2020
Accepted: 15 March 2021
Published: 29 April 2021
Citation:
Liu Y, Jiang G, Wang F and An X
(2021) Quantitative Assessment of
Changes in Hemodynamics After
Obliteration of Large Intracranial
Carotid Aneurysms Using
Computational Fluid Dynamics.
Front. Neurol. 12:632066.
doi: 10.3389/fneur.2021.632066
Quantitative Assessment of Changes
in Hemodynamics After Obliteration
of Large Intracranial Carotid
Aneurysms Using Computational
Fluid Dynamics
Yongsheng Liu*†, Guinan Jiang †, Feng Wang*and Xiangbo An
Department of Interventional Neuroradiology, First Affiliated Hospital of Dalian Medical University, Dalian, China
Background: It was speculated that the alteration of the geometry of the artery might
lead to hemodynamic changes of distal arteries. This study was to investigate the
hemodynamic changes of distal arterial trees, and to identify the factors accounting for
hyperperfusion after the obliteration of large intracranial aneurysms.
Methods: We retrospectively reviewed data of 12 patients with intracranial carotid
aneurysms. Parametric models with intracranial carotid aneurysm were created.
Patient-specific geometries were generated by three-dimensional rotational angiography.
To mimic the arterial geometries after complete obliteration of the aneurysms,
the aneurysms were virtually removed. The Navier–Stokes equations were solved
using ANSYS CFX 14. The average wall shear stress, pressure and flow velocity
were measured.
Results: Pressure ratio values were significantly higher in A1 segments, M1 segments,
and M2 +M3 segments after obliteration of the aneurysms (p=0.048 in A1 segments,
p=0.017 in M1 segments, p=0.001 in M2 +M3 segments). Velocity ratio values
were significantly higher in M1 segments and M2 +M3 segments after obliteration of
the aneurysms (p=0.047 in M1 segments, p=0.046 in M2 +M3 segments). The
percentage of pressure ratio increase after obliteration of aneurysms was significantly
correlated with aneurysmal angle (r=0.739, p=0.006 for M2 +M3).
Conclusions: The pressure and flow velocity of distal arterial trees became higher after
obliteration of aneurysms. The angle between the aneurysm and the parent artery was
the factor accounting for pressure increase after treatment.
Keywords: carotid artery, hemodynamics, large intracranial aneurysm, computational fluid dynamics, geometry
INTRODUCTION
Intracranial aneurysm is a common disease in the general population (1). Cerebral hyperperfusion
syndrome (HPS) and remote intracerebral hemorrhage (ICH) after treatment of the large
intracranial aneurysm have been noted (2–5). The mechanism remains unknown, but it was
speculated that the alteration of the geometry of the artery might lead to hemodynamic changes

Liu et al. Hemodynamics After Obliteration of Aneurysms
of distal arterial trees, which may contribute to cerebral HPS
and remote ICH; nonetheless, this speculation has not been well
studied (2,4,6–8).
With the development of computational fluid dynamics
(CFD) and three-dimensional imaging technology, patient-
specific hemodynamic analysis has become feasible. However,
quantitative study of the hemodynamic changes that occur in
the region distal to the aneurysms after the obliteration of large
intracranial aneurysms is relatively rare (6).
The aim of our study was to investigate the hemodynamic
changes of distal arterial trees after the obliteration of large
intracranial carotid aneurysms and to identify the factors
accounting for hyperperfusion after the obliteration of large
intracranial carotid aneurysms.
METHODS
Patient Selection
We retrospectively reviewed data of 12 patients with large
intracranial aneurysms of internal carotid artery (ICA) between
August 2018 and August 2019 in our institution.
Inclusion criteria were unilateral intracranial aneurysms
of ICA and the maximum diameter of aneurysm ≥10 mm.
Exclusion criteria were stenosis of ICA and multiple
cerebral aneurysms.
Modeling of the Aneurysms and
Hemodynamic Parameter Calculations
The angles between parent artery and the aneurysm
were measured.
Parametric models with an aneurysm of ICA (15–10–10 mm)
derived from patient 11 were created using SolidWorks software
(SolidWorks Co, Concord, MA, USA). Three models were
created with aneurysmal angles of 45◦, 90◦, and 135◦(Figure 1).
Patient-specific geometries were generated by three-
dimensional rotational angiography. The surface images
were reconstructed using Mimics software (Materialize Co.,
Leuven, Belgium). To mimic the arterial geometries after
complete obliteration of the aneurysms, the aneurysms were
virtually removed.
FIGURE 1 | Models with aneurysmal angles of 45◦(A), 90◦(B), and 135◦(C).
After segmenting and surface smoothing by Geomagic
Studio 9.0 software (Geomagic USA), the geometries in
stereolithography (STL) format were then exported to
ICEM CFD 14.0 (ANSYS, Inc., Canonsburg, PA, USA) for
meshing. The vessels were assumed to be rigid with no-slip
boundary conditions.
The blood was assumed as incompressible fluid with a density
of 1,025 kg/m3and a viscosity of 0.0035 Pa s. The walls of the
patient geometry were assumed as rigid (9). The inlet boundary
condition used mass-flow boundary condition (245 ml/min) (10),
whereas the outlet boundary condition used pressure outlet with
zero pressure. The Navier–Stokes equations were solved using
ANSYS CFX 14.0 (ANSYS, Inc., Canonsburg, PA, USA).
The beginning part of the cavernous segment of ICA was
defined as the origin plane.
The average wall shear stress (WSS), pressure, and flow
velocity were measured. We therefore normalized them to
achieve the relative indices such as WSS ratio, velocity ratio and
pressure ratio, divided by the values of the corresponding origin
plane (11).
Statistical Analysis
Comparisons of hemodynamic parameters of the middle
cerebral arteries (MCAs) and anterior cerebral arteries (ACAs)
between the pre-obliteration group and post-obliteration group
were performed.
SPSS 19.0 software (SPSS Inc., Chicago, IL, USA) was used
for statistical analyses. Statistical significance was assessed by
the application of paired t-tests comparing the hemodynamics
between the pre-obliteration group and post-obliteration group.
The association between the percentage of pressure ratio increase
after obliteration of aneurysms and aneurysmal angles was
quantified using Pearson’s correlation coefficients. All tests used
a significance level of p<0.05.
RESULTS
Patient Characteristics
The study population comprised 12 patients, including nine
females (75%) and three males (25%). The patient characteristics
and the aneurysm features are summarized in Table 1.
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Liu et al. Hemodynamics After Obliteration of Aneurysms
TABLE 1 | Characteristics of the study population.
Subject Sex Age (y) Smoking Diabetes mellitus Hypertension Location Side Size (mm) Aneurysmal angle (◦)
1 M 53 Yes Yes Yes Cavernous R 14–13–10 41
2 F 73 No No Yes Posterior communicating L 12–8–7 79
3 F 61 No No Yes Ophthalmic L 11–6–6 71
4 F 40 No No No Posterior communicating L 10–6–5 82
5 F 53 No No No Posterior communicating R 23–20–16 95
6 F 57 No No No Ophthalmic L 20–20–17 96
7 F 52 No No No Posterior communicating L 11–7–7 135
8 F 65 No No Yes Posterior communicating L 20–20–17 51
9 M 54 Yes No No Posterior communicating R 21–14–10 65
10 F 72 No No Yes Paraclinoid R 13–10–7 105
11 M 62 No No Yes Posterior communicating R 11–8–8 96
12 F 66 No No Yes Posterior communicating L 13–11–9 80
L, left; R, right.
TABLE 2 | Hemodynamic changes in the distal arteries after obliteration of
aneurysms.
Mean ±SD P-value
Pre-obliteration Post-obliteration
A1 segments
WSS ratio 3.33 ±3.84 3.25 ±3.11 0.732
Pressure ratio 0.56 ±0.18 0.62 ±0.21 0.048
Velocity ratio 1.35 ±0.64 1.38 ±0.57 0.368
A2 segments
WSS ratio 2.11 ±2.01 2.11 ±1.77 0.952
Pressure ratio 0.44 ±0.14 0.46 ±0.15 0.129
Velocity ratio 1.10 ±0.45 1.16 ±0.41 0.190
A3 segments
WSS ratio 2.21 ±2.88 2.16 ±2.48 0.730
Pressure ratio 0.28 ±0.16 0.27 ±0.10 0.746
Velocity ratio 1.05 ±0.61 1.13 ±0.16 0.246
M1 segments
WSS ratio 4.48 ±5.49 4.02 ±3.33 0.519
Pressure ratio 0.53 ±0.16 0.59 ±0.19 0.017
Velocity ratio 1.61 ±0.76 1.69 ±0.72 0.047
M2 +M3 segments
WSS ratio 1.94 ±1.84 2.04 ±1.78 0.076
Pressure ratio 0.35 ±0.17 0.39 ±0.17 0.001
Velocity ratio 0.99 ±0.41 1.09 ±0.40 0.046
Hemodynamics
The WSS ratio, velocity ratio, and pressure ratio values were
analyzed (Table 2,Figures 2,3). Statistical analysis demonstrated
that pressure ratio values were significantly higher in A1
segments, M1 segments, and M2 +M3 segments after
obliteration of the aneurysms (p=0.048 in A1 segments, p=
0.017 in M1 segments, p=0.001 in M2 +M3 segments). Velocity
ratio values were significantly higher in M1 segments and M2 +
M3 segments after obliteration of the aneurysms (p=0.047 in
M1 segments, p=0.046 in M2 +M3 segments). The WSS ratio
values were similar in MCAs and ACAs for both groups (Table 2).
CFD study of the parametric models showed that an
increasing aneurysmal angle yielded a lower pressure ratio of
ACAs and MCAs (Figure 4). Therefore, the aneurysmal angle
might influence the pressure change of distal arterial trees after
obliteration of aneurysms.
The percentage of the pressure ratio increase after obliteration
of aneurysms was significantly correlated with aneurysm angle
(r=0.739, p=0.006 for M2 +M3) (Figure 5). The
percentage of the pressure ratio increase after obliteration
of aneurysms was not significantly correlated with aneurysm
volume (Pearson r= −0.018, p=0.958 for A1; r= −0.035,
p=0.914 for M1; r= −0.139, p=0.667 for M2 +M3). The
percentage of the pressure ratio increase in A1 and M1 segments
after obliteration of aneurysms was not significantly correlated
with aneurysmal angle (r= −0.113, p=0.741 for A1; r= −0.022,
p=0.945 for M1). The percentage of the pressure velocity
increase after obliteration of the aneurysms was not significantly
correlated with the aneurysm angle (r= −0.549, p=0.065 for
M2 +M3).
DISCUSSION
Cerebral HPS and remote ICH are unpredictable and potentially
severe complications after treatment of the large intracranial
aneurysm. Among all the possible etiologies (2,12–14),
hemodynamic changes have been proposed as a possible
candidate, but no mechanism has been well-studied (15).
The relationship of geometry and hemodynamics is mutually
causal. The hemodynamics of arteries distal to the aneurysms
may be changed after obliteration of aneurysms. Many studies
have concentrated on the hemodynamic changes within the
aneurysms after treatment of intracranial aneurysms. However,
hemodynamic changes within distal arterial trees after aneurysm
treatment are much less understood.
The incidence of remote ICH appears to be higher for large
aneurysms than for small aneurysms (8,14–16). Therefore, we
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Liu et al. Hemodynamics After Obliteration of Aneurysms
FIGURE 2 | Comparison of the pressure ratio and velocity ratio after obliteration of aneurysms. (A) A1 segments. (B) M1 segments. (C) M2 +M3 segments. (D) M2
+M3 segments.
FIGURE 3 | Example of simulation results of patient 11. The pressure ratio in the arteries distal to aneurysm became higher after the aneurysm was obliterated. (A)
The pressure ratio before obliteration of the aneurysm. (B) The pressure ratio after obliteration of the aneurysm.
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Liu et al. Hemodynamics After Obliteration of Aneurysms
FIGURE 4 | Pressure ratio of the models with aneurysmal angles of 45◦, 90◦, 135◦, and the no-aneurysm model. (A) A1 segment. (B) A2 segment. (C) A3 segment.
(D) M1 segment. (E) M2 +M3 segments.
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Liu et al. Hemodynamics After Obliteration of Aneurysms
FIGURE 5 | The relationship between the aneurysmal angles and the pressure
ratio increase rates in M2 +M3 segments after obliteration of the aneurysms.
The correlation coefficient was r=0.739.
hypothesized that pressure and velocity of distal arteries might
become higher after obliteration of large aneurysms.
After obliteration of aneurysms, blood flow through the
vessels distal to the aneurysms may suddenly increase. Increased
flow rate and pressure distal to the aneurysms after clipping
or endovascular treatment have been demonstrated in several
studies. Brunozzi et al. reported that the ratio of ipsilateral MCA
to systemic systolic and mean blood pressure increased after flow
diverter device deployment (7). In our study, statistical analysis
demonstrated that pressure ratio values became higher in MCAs
and A1 segments after obliteration of aneurysms. Compared to
the ACAs, MCAs had a higher pressure increase, indicating the
higher risk of HPS in the areas supplied by MCAs.
There are few findings regarding risk factors of the appearance
of hyperperfusion after obliteration of aneurysms (7). Brunozzi
et al. reported that the hemodynamic changes in the arteries
distal to the aneurysms after flow diverter device deployment
were independent from aneurysm size (7). Our CFD study of the
models suggested that a large aneurysm can induce pressure loss,
resulting in hyperperfusion after obliteration of aneurysm. The
aneurysmal angle was the factor accounting for pressure loss.
According to the results of our study, the percentage of the
pressure ratio increase after obliteration of aneurysms was not
correlated with aneurysm volume. Our study suggested that
the angle between the aneurysm and the parent artery was the
factor accounting for the pressure increase after obliteration of
aneurysms. It was only a preliminary finding based on the results
of our study. Further studies are required to identify which
patients are at a higher risk of hyperperfusion after obliteration
of aneurysms.
Brunozzi et al. demonstrated that the mean flow velocity of
MCA increased especially in patients with delayed ipsilateral ICH
after flow diverter device deployment (6). Chiu et al. reported a
case of increasing cerebral blood flow and cerebral blood volume
distal to the aneurysm after flow diverter treatment (3). In our
study, velocity ratio values became higher in M2 +M3 segments
after obliteration of aneurysms.
Prevention of HPS is critical. Several investigators have found
that careful monitoring and comprehensive management of
blood pressure can lower the incidence of HPS after carotid
artery stenting (17,18). Blood pressure reduction may lower the
pressure of cerebral arteries and reduce the risk of HPS after
obliteration of aneurysms.
WSS can be viewed as the frictional force applied against the
vascular wall by the movement of blood. Study of the WSS of
the arteries distal to the aneurysms after the obliteration of large
intracranial aneurysms is sparse. In a study by Shakur et al., the
WSS values were higher in the ipsilateral MCA among patients
with hemorrhage after flow diverter device placement (19). Our
study demonstrated that the WSS ratio values were similar in
MCAs and ACAs for both groups.
Limitations to this study include its retrospective nature, a
small sample size, and single institution design. Further study
with a larger number of patients would be necessary to validate
our findings. Patient-specific flow-boundary information was
unavailable, which might affect the results. Virtual aneurysm
removal might underestimate or overestimate the size of the
healthy lumen. This study only involved large intracranial
aneurysms of ICAs, which limited the generalization of the
study results.
CONCLUSION
Pressure ratio values became higher in MCAs and A1 segments
after obliteration of large intracranial carotid aneurysms. The
angle between the aneurysm and the parent artery was the
factor accounting for the pressure increase after treatment.
Velocity ratio values became higher in M2 +M3 segments after
obliteration of aneurysms.
DATA AVAILABILITY STATEMENT
The raw data supporting the conclusions of this article will be
made available by the authors, without undue reservation.
ETHICS STATEMENT
The studies involving human participants were reviewed and
approved by Ethics Committee of First Affiliatted Hospital
of Dalian Medical University. Written informed consent for
participation was not required for this study in accordance with
the national legislation and the institutional requirements.
AUTHOR CONTRIBUTIONS
YL and GJ carried out the simulation study and drafted the
manuscript. GJ and XA performed the data collection and data
analysis. YL and FW participated in the design of this study. XA
helped to check the manuscript. All authors contributed to the
article and approved the submitted version.
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Liu et al. Hemodynamics After Obliteration of Aneurysms
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Conflict of Interest: 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.
Copyright © 2021 Liu, Jiang, Wang and An. This is an open-accessa rticle distributed
under the terms of the Creative Commons Attribution License (CC BY). The use,
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author(s) and the copyright owner(s) are credited and that the original publication
in this journal is cited, in accordance with accepted academic practice. No use,
distribution or reproduction is permitted which does not comply with these terms.
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