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Hemodynamics in Ruptured Intracranial Aneurysms with Known Rupture Points
Original Article
Hemodynamics in Ruptured Intracranial Aneurysms with Known Rupture Points Miao Li1,2, Jie Wang3, Jian Liu1, Conghai Zhao2, Xinjian Yang1
BACKGROUND: Hemodynamics plays an important role in aneurysm rupture. Microsurgical clipping provides the best chance to confirm the rupture point. The aim of this study was to explore the associations between the rupture point and hemodynamics.
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METHODS: Computational fluid dynamic simulations were performed on 16 intracranial aneurysms. The rupture point was detected at the time of clipping by 3 independent neurosurgeons. Hemodynamic parameters, including wall shear stress (WSS) and oscillatory shear index (OSI), were calculated at the rupture point and the whole aneurysm sac. Intra-aneurysmal flow patterns and flow impingement were also studied.
study on the rupture risk assessment is still needed with more data and detailed information.
-
RESULTS: The time-averaged WSS was 3.4855 3.8881 Pa at the aneurysm sac, which was significantly larger than that at the rupture point (1.5403 2.3688 Pa, P [ 0.002). The OSI at the rupture point (0.0354 0.0459) was larger than at the sac (0.0220 0.0232) without difference. Thirteen aneurysms (81.3%) showed a complex flow pattern in the aneurysm sac; however, more than two thirds of the cases (68.7%) did not show a flow impact at the rupture point. Of these cases with daughter blebs, the rupture points were confirmed at the blebs in 6 cases. Two cases did not show association between blebs and rupture point.
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CONCLUSIONS: The hemodynamic characteristics at the rupture point were different from the aneurysm sac, and the WSS was significantly lower at the rupture point. Further
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Key words - Computational fluid dynamics - Hemodynamics - Intracranial aneurysm - Rupture point - Wall shear stress Abbreviations and Acronyms 3D: 3-Dimensional 3D-CTA: 3-Dimensional computed tomography angiography CFD: Computational fluid dynamics OSI: Oscillatory shear index WSS: Wall shear stress
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INTRODUCTION
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upture of intracranial aneurysms leads to severe morbidity and mortality.1,2 Accurate determination of the potential risk of aneurysm rupture has clinical significance. Morphologic characteristics, such as a larger aneurysm size or irregular shape with daughter blebs, have been widely used in decision-making regarding the treatment of unruptured aneurysms.3,4 However, many ruptured aneurysms are small.5,6 Three-dimensional (3D) imaging has been used to demonstrate additional morphologic details, such as daughter blebs or relationship of the aneurysm sac and side branch.7 Moreover, 3D imaging can be used in hemodynamic studies as the patient-specific aneurysm geometric model.8,9 Computational fluid dynamics (CFD) has been used to explore the effects of hemodynamics on aneurysm rupture, and hemodynamics has been shown to play an important role in the rupture event.8-11 Many hemodynamic parameters are reportedly associated with aneurysm rupture, including wall shear stress (WSS), oscillatory shear index (OSI), and energy loss.4,8,9,11 However, previous studies depicted these hemodynamic characteristics from the whole aneurysm sac, which were then used to compare between ruptured and unruptured aneurysms. Considering the blood was usually spilled out of the aneurysm sac from a single point, comparison with the result from the whole sac might introduce
From the 1Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tian Tan Hospital, Capital Medical University, Beijing; and Departments of 2 Neurosurgery and 3Neurology, China-Japan Union Hospital, Jilin University, Changchun, China To whom correspondence should be addressed: Xinjian Yang, M.D., Ph.D. [E-mail: [email protected]] Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.07.026 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
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bias. Therefore, more detailed elucidation of the hemodynamic characteristics of the rupture point is needed. Although some advanced techniques or methods are used, the detection of the rupture point is indirect and somehow less accurate on the angiographic images. Sometimes, the daughter bleb was regarded as the rupture point on the images, which was ultimately confirmed incorrect during surgical clipping. The most accurate way to confirm the rupture point was detection during clipping. Clinically, encountering a ruptured intracranial aneurysm with a known rupture point is not rare during surgical clipping, especially aneurysms under well exposure. To our knowledge, however, fewer researchers have applied CFD to explore the effects of hemodynamics on the rupture point.12-17 We identified only 6 studies involving 30 cases in the literature.12-17 Of these data, only 2 studies with 18 cases were analyzed based on the surgical inspection of the rupture point.12-17 Therefore, in the present study, we performed CFD simulations based on patient-specific models obtained from preoperative 3-dimensional computed tomography angiography (3D-CTA) and aimed to characterize the relationship between hemodynamic characteristics and the rupture point observed during microsurgical clipping. MATERIALS AND METHODS Patients From April 2014 to May 2015, 79 ruptured intracranial aneurysms were diagnosed by 3D-CTA, and clipping surgeries were performed in 57 cases. The aneurysms were included in this study according to the following criteria: 1) detection of the apparent rupture point during clipping surgery or on intraoperative videos by 3 independent neurosurgeons and 2) availability of preoperative 3D-CTA data with adequate image quality for generation of an aneurysm geometry model. If apparent differences in assessment of the rupture point could not be resolved by consensus, the cases were excluded from the study. At this point, 16 patients with 16 aneurysms were included and analyzed in this study. Another 41 aneurysms were excluded because of failed detection of an apparent rupture point during surgery (n ¼ 27; 24 of them were excluded because of failed observation of rupture point, and 3 of them were excluded because of a lack of consensus) and poor imaging quality (n ¼ 14). The ethics committee of the China-Japan Union Hospital of Jilin University approved this study, and informed consent was obtained from the patients and their relatives. Patient-Specific Modeling of Aneurysms and Numerical Simulation Preoperative 3D-CTA examinations were performed with a 64-detector multislice computed tomography scanner (Discovery CT 750HD [GE Healthcare, Milwaukee, Wisconsin, USA]). The study parameters included radiation parameters of AutomA and 100 kV, matrix size of 512 512, field of view of 25 cm, slice thickness of 0.625 mm, helical pitch of 0.984:1, and isotropic voxel size of 0.625 mm. A total of 60 mL of contrast material followed by 30 mL of saline solution was injected into the antecubital vein at a rate of 4.5 mL/s with a power injection platform (Ulrich Tennessee XD2003 [Ulrich GmbH & Co. KG,
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Ulm, Germany]). The 3D-CTA data were recorded as Digital Imaging and Communications in Medicine files and transferred to a workstation (GE AW 4.5 [GE Healthcare]) equipped with software developed in-house by Capital Medical University to create stereolithography files containing blood vessel luminal surface data. These stereolithography files were then imported into ICEM CFD software (ANSYS Inc., Canonsburg, Pennsylvania, USA) to create 2.5 million finite-volume tetrahedral element grids with 3 prism layer elements for CFD simulations. CFX 14.0 software (ANSYS Inc.) was then used to solve the flow-governing NavierStokes equations with the assumption of laminar, incompressible, and Newtonian blood flow. The density and dynamic viscosity of the blood were set at 1060 kg/m3 and 0.004 N$s/m2, respectively. The blood vessel wall was assumed to be rigid with no-slip boundary conditions. The pulsatile velocity profile obtained by transcranial Doppler from a normal subject was applied for the inflow boundary conditions. Three cardiac cycle simulations were performed for numerical stability, and the last cardiac cycle was collected as output.
Definition of Rupture Point During microsurgical clipping or via intraoperative videos, the rupture point was detected as a point of tight adhesion of the thin, disrupted aneurysmal wall of a hematoma or white thrombus.18 Three independent neurosurgeons evaluated the operation videos with definition. The aneurysm 3D images could be transferred to the same angle and coordination according to the 2-dimensional video. Each neurosurgeon then determined each location of the rupture point on the patient-specific geometry model used to perform the CFD simulation. An area with the same size of the hematoma or white thrombus was marked by a circle point. In fact, the rupture point is not a real point, but an area. It is an incomplete aneurysm wall with the adhesion of the sludged blood. Apparent differences in assessment of the rupture point were resolved by consensus; if consensus could not be reached, the cases were excluded from the study. For each aneurysm, the neck width and aneurysm size were measured from the 3D-CTA image, and the aspect ratio (aneurysm size/ neck width) was calculated accordingly.
Hemodynamic Parameters and Data Analysis The hemodynamic characteristics at the rupture point and the whole aneurysm dome were calculated for comparison. The time-averaged WSS was measured in each region. The OSI was calculated to investigate the changes in the WSS vector within the cardiac cycle. The intra-aneurysmal flow structure was also evaluated to determine the flow impingement, and the contour of velocity was depicted on a cutting plane. Statistical analysis of the parameters at each region was performed using a paired Student t test. Pearson correlation coefficients were calculated between the morphologic parameters and the hemodynamic variables at both the rupture point and the aneurysm dome. Statistical significance was considered present at P < 0.05.
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ORIGINAL ARTICLE MIAO LI ET AL.
HEMODYNAMICS ON RUPTURE POINTS
RESULTS Of all included patients, 31.3% were men. The average age was 52.6 years (range, 36e68 years). Because of easier exposure and more indication for microsurgical clipping, 87.5% of the aneurysms were located at the middle cerebral artery (14/16). Eleven patients had Hunt-Hess grade 2, 3 patients had grade 3, and 2 patients had grade 4. The mean aneurysm size was 6.9 mm (range, 2.7e20.0 mm), and the mean aneurysm neck was 4.7 mm (range, 2.0e8.0 mm). The mean aspect ratio was 1.5. Three patients had multiple aneurysms, and 50% of the aneurysms were irregular in shape with daughter blebs. Of these cases with daughter blebs, the rupture points were confirmed at the blebs in 6 cases. Two cases did not show association between the blebs and rupture point. The rupture point is near to the turning of the blood inflow tract. The patient demographics and morphology of the aneurysms are shown in Table 1. The hemodynamics results of the 16 included aneurysms are shown in Table 2. The time-averaged WSS was 3.4855 3.8881 Pa at the aneurysm sac, which was significantly larger than that at the rupture point (1.5403 2.3688 Pa, P ¼ 0.002) (Table 3). The OSI at the sac and rupture point was also calculated. The OSI at the rupture point (0.0354 0.0459) was larger than at the sac (0.0220 0.0232). However, the difference was not significant (P ¼ 0.286) (Table 3). The hemodynamics findings in case 1 are shown in Figure 1. The intra-aneurysmal flow streamlines showed that 13 aneurysms (81.3%) had a complex flow pattern with more than 1 vortex
flow structure. On the cutting planes, only 5 cases (31.3%) showed a concentrated flow impact near the region of the rupture point. Most (68.7%) of the rupture points did not show direct flow impact with lower WSS. Pearson correlation analysis was performed between the morphologic and hemodynamic parameters. However, no significant correlation was found between these parameters.
DISCUSSION In this study, we evaluated a series of ruptured aneurysms in which the rupture points were confirmed during microsurgical clipping and used CFD to evaluate the hemodynamic characteristics at the rupture point. According to our results, the rupture point was associated with a lower WSS than at the aneurysm sac. The rupture point was confirmed as located at the daughter bleb in 75% of cases. To our knowledge, this is the largest case series to reveal the detailed hemodynamic characteristics around the rupture point. The hemodynamic characteristics associated with aneurysm rupture have been widely studied. However, the results are controversial.8,9,19,20 A CFD study by Cebral et al.19 showed that ruptured aneurysms were more likely to have a larger maximum WSS. However, Xiang et al.8 reported that low WSS was a risk factor for aneurysm rupture. Hemodynamic studies using preruptured aneurysm models also showed that low WSS was a risk factor for aneurysm rupture.9,11 All of these results demonstrate the hemodynamic features of the whole aneurysm sac
Table 1. Summary of Patient Demographics and Morphology Case Number
Age (Years)
Site
Smoke
Drink
HTN
DM
Hunt-Hess Grade
Multiple Aneurysms
Aneurysm Shape
Size (mm)
Neck (mm)
AR
1
56e60
RMCA
Yes
No
Yes
Yes
2
No
I
10
5
2.00
2
46e50
LMCA
No
No
Yes
No
2
No
R
4.8
2.7
1.78
3
66e70
RMCA
No
Yes
No
No
2
No
I
6
7
0.86
4
60e65
LMCA
No
No
No
No
2
No
R
7.2
5.5
1.31
5
50e55
RMCA
No
No
Yes
No
2
No
R
4.2
2.3
1.83
6
50e55
RMCA
No
No
No
No
3
No
R
2.7
2.2
1.23
7
36e40
RICA-Bifur
No
No
No
No
2
Yes
R
3
3
1.00
8
36e40
RMCA
No
No
No
No
2
No
R
4
3.5
1.14
9
50e55
LMCA
No
No
No
Yes
4
No
R
5
3
1.67
10
66e70
RMCA
No
No
No
Yes
2
No
I
6.5
5.5
1.18
11
40e45
RMCA
No
No
Yes
No
2
No
I
5
2
2.50
12
60e65
LMCA
No
No
Yes
No
4
No
I
12
8
1.50
13
60e65
RMCA
No
No
Yes
No
3
No
I
20
8
2.50
14
40e45
LMCA
No
No
No
Yes
3
No
R
5.6
4.2
1.33
15
40e45
ACOM
No
No
Yes
Yes
2
Yes
I
7.2
5
1.44
16
50e55
RMCA
No
No
Yes
Yes
2
Yes
I
7.5
7.5
1.00
HTN, hypertension; DM, diabetes mellitus; AR, aspect ratio; RMCA, right middle cerebral artery; I, irregular; LMCA, left middle cerebral artery; R, regular; RICA-Bifur, right internal carotid artery bifurcation; ACOM, anterior communicating artery.
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Table 2. Summary of Hemodynamic Results Case Number
aTAWSS (Pa)
aOSI
rTAWSS (Pa)
rOSI
Flow Pattern
Impact on RP
1
1.2968
0.0183
0.6616
0.0058
C
No
2
1.5186
0.0072
0.3159
0.0455
S
Yes
3
0.5284
0.0343
0.0752
0.0537
C
No
4
1.8796
0.0703
1.3948
0.0000
C
No
5
4.5156
0.0033
1.8986
0.0157
S
Yes
6
1.1701
0.0099
0.1237
0.0043
C
No
7
0.7996
0.0787
0.1399
0.0203
C
No
8
0.5943
0.0292
0.0005
0.1782
C
No
9
0.4397
0.0381
0.0011
0.1029
C
No
10
3.3722
0.0046
1.4934
0.0148
C
No
11
8.0132
0.0087
1.8149
0.0124
C
Yes
12
10.3241
0.0075
7.8421
0.0135
C
Yes
13
0.7216
0.0016
0.5180
0.0127
C
Yes
14
12.3071
0.0156
6.8720
0.0315
S
No
15
7.4533
0.0084
1.1788
0.0115
C
No
16
0.8344
0.0164
0.3142
0.0442
C
No
aTAWSS, time-averaged wall shear stress at the aneurysm dome; aOSI, oscillatory shear index at the aneurysm dome; rTAWSS, time-averaged wall shear stress at the rupture point; rOSI, oscillatory shear index at the rupture point; RP, rupture point; C, complex flow pattern; S, simple flow pattern.
without knowing the location of the rupture point. Therefore, the detailed and accurate hemodynamic characteristics of the rupture point were unknown in those studies, which might contribute to the controversial results. Therefore, the hemodynamic characteristics at the rupture point have been less thoroughly studied and are needed. To our knowledge, only a total of 30 cases from 6 studies, including single case reports, have been analyzed with respect to the hemodynamics at the rupture point based on different inspection methods of the rupture point.17 However, the findings remain controversial, and one of the reasons might be the different inspection methods of the rupture point. Of these 6 studies, only 2 were based on the microsurgical inspection of the rupture point, which might be more accurate. Cebral et al.12 reported 9 cases in which the rupture point was inspected in volume-rendered 3D images without surgical confirmation. Their results showed that the rupture point in 8 of 9 aneurysms (89%) had thinner and stiffer walls in regions of abnormally high WSS. Fukazawa et al.13 and Omodaka et al.16 reported 12 and 6 cases, respectively. The rupture point was confirmed during surgical clipping in both studies. Low WSS was revealed at the rupture point in both studies. Similar results were found in the present series, and the rupture point showed lower WSS than the aneurysm sac. The OSI at the rupture point was higher than that at the sac; however, the difference was not statistically significant. WSS is one of the most thoroughly evaluated parameters in hemodynamic studies and is thought to play an important role in aneurysm rupture.8,9,17,19 WSS is the frictional force of viscous
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blood on endothelial cells and can modulate the cellular functions of the vessel wall.8,21 Low WSS can increase endothelial permeability and promote inflammatory cell infiltration.22,23 Such a remodeling process may lead to further rupture.24,25 This study has several limitations. First, the retrospective study design and sample size may have introduced bias. Further studies with larger sample sizes are needed to investigate the hemodynamic characteristics of the rupture point, and bias from the statistical analysis with such a small sample size may be solved in the future. Second, in addition to hemodynamic factors, other pathophysiologic factors may have also been involved in the rupture mechanism. Finally, some of the assumptions used in the simulations, such as a rigid wall, laminar flow, and Newtonian blood flow, might have also introduced bias. CONCLUSIONS We have presented a series of cases in which the rupture point was identified during surgical clipping. The hemodynamic Table 3. Comparisons for Hemodynamic Parameters Examined Between Rupture Point and Aneurysm Dome Parameters
Rupture Point
Aneurysm Dome
P Value
TAWSS (Pa)
1.5403 2.3688
3.4855 3.8881
0.002
OSI
0.0354 0.0459
0.0220 0.0232
0.286
Values are mean SD or as otherwise indicated. TAWSS, time-averaged wall shear stress; OSI, oscillatory shear index.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.07.026
ORIGINAL ARTICLE MIAO LI ET AL.
HEMODYNAMICS ON RUPTURE POINTS
Figure 1. Wall shear stress distribution (A), oscillatory shear index (B), flow impingement (C), and streamlines (D) of case 1. The rupture point was detected via intraoperative video (E). Arrows show the rupture point. Low
characteristics at the rupture point were different from the aneurysm sac, and the WSS was significantly lower at the rupture
2. Juvela S, Poussa K, Lehto H, Porras M. Natural history of unruptured intracranial aneurysms: a long-term follow-up study. Stroke. 2013;44: 2414-2421. 3. Dhar S, Tremmel M, Mocco J, Kim M, Yamamoto J, Siddiqui AH, et al. Morphology parameters for intracranial aneurysm rupture risk assessment. Neurosurgery. 2008;63:185-196 [discussion: 196-197]. 4. Liu J, Xiang J, Zhang Y, Wang Y, Li H, Meng H, et al. Morphologic and hemodynamic analysis of
point. Further study on the rupture risk assessment is still needed with more data and detailed information.
paraclinoid aneurysms: ruptured versus unruptured. J Neurointerv Surg. 2014;6:658-663.
REFERENCES 1. Bederson JB, Awad IA, Wiebers DO, Piepgras D, Haley EC Jr, Brott T, et al. Recommendations for the management of patients with unruptured intracranial aneurysms: a statement for healthcare professionals from the stroke council of the american heart association. Circulation. 2000;102: 2300-2308.
wall shear stress was found at the rupture point without flow impact. OSI, oscillatory shear index; WSS, wall shear stress.
5. Weir B, Disney L, Karrison T. Sizes of ruptured and unruptured aneurysms in relation to their sites and the ages of patients. J Neurosurg. 2002;96: 64-70. 6. van Rooij WJ, Keeren GJ, Peluso JP, Sluzewski M. Clinical and angiographic results of coiling of 196 very small (< or ¼ 3 mm) intracranial aneurysms. AJNR Am J Neuroradiol. 2009;30:835-839. 7. White PM, Teasdale EM, Wardlaw JM, Easton V. Intracranial aneurysms: CT angiography and MR angiography for detection prospective blinded comparison in a large patient cohort. Radiology. 2001;219:739-749. 8. Xiang J, Natarajan SK, Tremmel M, Ma D, Mocco J, Hopkins LN, et al. Hemodynamicmorphologic discriminants for intracranial aneurysm rupture. Stroke. 2011;42:144-152.
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9. Liu J, Fan J, Xiang J, Zhang Y, Yang X. Hemodynamic characteristics of large unruptured internal carotid artery aneurysms prior to rupture: a case control study. J Neurointerv Surg. 2016;8:367-372. 10. Miura Y, Ishida F, Umeda Y, Tanemura H, Suzuki H, Matsushima S, et al. Low wall shear stress is independently associated with the rupture status of middle cerebral artery aneurysms. Stroke. 2013;44:519-521. 11. Pereira VM, Brina O, Bijlenga P, Bouillot P, Narata AP, Schaller K, et al. Wall shear stress distribution of small aneurysms prone to rupture: a case-control study. Stroke. 2014;45:261-264. 12. Cebral JR, Vazquez M, Sforza DM, Houzeaux G, Tateshima S, Scrivano E, et al. Analysis of hemodynamics and wall mechanics at sites of cerebral aneurysm rupture. J Neurointerv Surg. 2015; 7:530-536. 13. Fukazawa K, Ishida F, Umeda Y, Miura Y, Shimosaka S, Matsushima S, et al. Using computational fluid dynamics analysis to
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characterize local hemodynamic features of middle cerebral artery aneurysm rupture points. World Neurosurg. 2015;83:80-86. 14. Hodis S, Uthamaraj S, Lanzino G, Kallmes DF, Dragomir-Daescu D. Computational fluid dynamics simulation of an anterior communicating artery ruptured during angiography. J Neurointerv Surg. 2014;6:e14. 15. Kono K, Fujimoto T, Shintani A, Terada T. Hemodynamic characteristics at the rupture site of cerebral aneurysms: a case study. Neurosurgery. 2012;71:E1202-E1208 [discussion: E1209]. 16. Omodaka S, Sugiyama S, Inoue T, Funamoto K, Fujimura M, Shimizu H, et al. Local hemodynamics at the rupture point of cerebral aneurysms determined by computational fluid dynamics analysis. Cerebrovasc Dis. 2012;34:121-129. 17. Zhang Y, Jing L, Zhang Y, Liu J, Yang X. Low wall shear stress is associated with the rupture of intracranial aneurysm with known rupture point: case report and literature review. BMC Neurol. 2016; 16:231. 18. Ishikawa T, Nakayama N, Yoshimoto T, Aoki T, Terasaka S, Nomura M, et al. How does spontaneous hemostasis occur in ruptured cerebral aneurysms? Preliminary investigation on 247
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clipping surgeries. Surg Neurol. 2006;66:269-275 [discussion: 275-276].
intracranial aneurysm rupture. J Neurosurg. 2004; 101:1018-1025.
19. Cebral JR, Mut F, Weir J, Putman C. Quantitative characterization of the hemodynamic environment in ruptured and unruptured brain aneurysms. AJNR Am J Neuroradiol. 2011;32:145-151.
25. Kataoka K, Taneda M, Asai T, Kinoshita A, Ito M, Kuroda R. Structural fragility and inflammatory response of ruptured cerebral aneurysms. A comparative study between ruptured and unruptured cerebral aneurysms. Stroke. 1999;30: 1396-1401.
20. Xiang J, Tutino VM, Snyder KV, Meng H. CFD: computational fluid dynamics or confounding factor dissemination? The role of hemodynamics in intracranial aneurysm rupture risk assessment. AJNR Am J Neuroradiol. 2014;35:1849-1857. 21. Shojima M, Oshima M, Takagi K, Torii R, Hayakawa M, Katada K, et al. Magnitude and role of wall shear stress on cerebral aneurysm: computational fluid dynamic study of 20 middle cerebral artery aneurysms. Stroke. 2004;35: 2500-2505.
Conflict of interest statement: This work was supported by the National Key Research Development Program (2016YFC1300800), the National Natural Science Foundation of China (816705049, 81371315, 81471167, and 81220108007), and the Special Research Project for Capital Health Development (2018-4-1077).
22. Malek AM, Alper SL, Izumo S. Hemodynamic shear stress and its role in atherosclerosis. JAMA. 1999;282:2035-2042.
Received 10 April 2018; accepted 3 July 2018
23. Nixon AM, Gunel M, Sumpio BE. The critical role of hemodynamics in the development of cerebral vascular disease. J Neurosurg. 2010;112:1240-1253.
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24. Pentimalli L, Modesti A, Vignati A, Marchese E, Albanese A, Di Rocco F, et al. Role of apoptosis in
Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.07.026
Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.07.026
Hemodynamics in Ruptured Intracranial Aneurysms with Known Rupture Points Miao Li1,2, Jie Wang3, Jian Liu1, Conghai Zhao2, Xinjian Yang1
BACKGROUND: Hemodynamics plays an important role in aneurysm rupture. Microsurgical clipping provides the best chance to confirm the rupture point. The aim of this study was to explore the associations between the rupture point and hemodynamics.
-
METHODS: Computational fluid dynamic simulations were performed on 16 intracranial aneurysms. The rupture point was detected at the time of clipping by 3 independent neurosurgeons. Hemodynamic parameters, including wall shear stress (WSS) and oscillatory shear index (OSI), were calculated at the rupture point and the whole aneurysm sac. Intra-aneurysmal flow patterns and flow impingement were also studied.
study on the rupture risk assessment is still needed with more data and detailed information.
-
RESULTS: The time-averaged WSS was 3.4855 3.8881 Pa at the aneurysm sac, which was significantly larger than that at the rupture point (1.5403 2.3688 Pa, P [ 0.002). The OSI at the rupture point (0.0354 0.0459) was larger than at the sac (0.0220 0.0232) without difference. Thirteen aneurysms (81.3%) showed a complex flow pattern in the aneurysm sac; however, more than two thirds of the cases (68.7%) did not show a flow impact at the rupture point. Of these cases with daughter blebs, the rupture points were confirmed at the blebs in 6 cases. Two cases did not show association between blebs and rupture point.
-
CONCLUSIONS: The hemodynamic characteristics at the rupture point were different from the aneurysm sac, and the WSS was significantly lower at the rupture point. Further
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Key words - Computational fluid dynamics - Hemodynamics - Intracranial aneurysm - Rupture point - Wall shear stress Abbreviations and Acronyms 3D: 3-Dimensional 3D-CTA: 3-Dimensional computed tomography angiography CFD: Computational fluid dynamics OSI: Oscillatory shear index WSS: Wall shear stress
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INTRODUCTION
R
upture of intracranial aneurysms leads to severe morbidity and mortality.1,2 Accurate determination of the potential risk of aneurysm rupture has clinical significance. Morphologic characteristics, such as a larger aneurysm size or irregular shape with daughter blebs, have been widely used in decision-making regarding the treatment of unruptured aneurysms.3,4 However, many ruptured aneurysms are small.5,6 Three-dimensional (3D) imaging has been used to demonstrate additional morphologic details, such as daughter blebs or relationship of the aneurysm sac and side branch.7 Moreover, 3D imaging can be used in hemodynamic studies as the patient-specific aneurysm geometric model.8,9 Computational fluid dynamics (CFD) has been used to explore the effects of hemodynamics on aneurysm rupture, and hemodynamics has been shown to play an important role in the rupture event.8-11 Many hemodynamic parameters are reportedly associated with aneurysm rupture, including wall shear stress (WSS), oscillatory shear index (OSI), and energy loss.4,8,9,11 However, previous studies depicted these hemodynamic characteristics from the whole aneurysm sac, which were then used to compare between ruptured and unruptured aneurysms. Considering the blood was usually spilled out of the aneurysm sac from a single point, comparison with the result from the whole sac might introduce
From the 1Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tian Tan Hospital, Capital Medical University, Beijing; and Departments of 2 Neurosurgery and 3Neurology, China-Japan Union Hospital, Jilin University, Changchun, China To whom correspondence should be addressed: Xinjian Yang, M.D., Ph.D. [E-mail: [email protected]] Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.07.026 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
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bias. Therefore, more detailed elucidation of the hemodynamic characteristics of the rupture point is needed. Although some advanced techniques or methods are used, the detection of the rupture point is indirect and somehow less accurate on the angiographic images. Sometimes, the daughter bleb was regarded as the rupture point on the images, which was ultimately confirmed incorrect during surgical clipping. The most accurate way to confirm the rupture point was detection during clipping. Clinically, encountering a ruptured intracranial aneurysm with a known rupture point is not rare during surgical clipping, especially aneurysms under well exposure. To our knowledge, however, fewer researchers have applied CFD to explore the effects of hemodynamics on the rupture point.12-17 We identified only 6 studies involving 30 cases in the literature.12-17 Of these data, only 2 studies with 18 cases were analyzed based on the surgical inspection of the rupture point.12-17 Therefore, in the present study, we performed CFD simulations based on patient-specific models obtained from preoperative 3-dimensional computed tomography angiography (3D-CTA) and aimed to characterize the relationship between hemodynamic characteristics and the rupture point observed during microsurgical clipping. MATERIALS AND METHODS Patients From April 2014 to May 2015, 79 ruptured intracranial aneurysms were diagnosed by 3D-CTA, and clipping surgeries were performed in 57 cases. The aneurysms were included in this study according to the following criteria: 1) detection of the apparent rupture point during clipping surgery or on intraoperative videos by 3 independent neurosurgeons and 2) availability of preoperative 3D-CTA data with adequate image quality for generation of an aneurysm geometry model. If apparent differences in assessment of the rupture point could not be resolved by consensus, the cases were excluded from the study. At this point, 16 patients with 16 aneurysms were included and analyzed in this study. Another 41 aneurysms were excluded because of failed detection of an apparent rupture point during surgery (n ¼ 27; 24 of them were excluded because of failed observation of rupture point, and 3 of them were excluded because of a lack of consensus) and poor imaging quality (n ¼ 14). The ethics committee of the China-Japan Union Hospital of Jilin University approved this study, and informed consent was obtained from the patients and their relatives. Patient-Specific Modeling of Aneurysms and Numerical Simulation Preoperative 3D-CTA examinations were performed with a 64-detector multislice computed tomography scanner (Discovery CT 750HD [GE Healthcare, Milwaukee, Wisconsin, USA]). The study parameters included radiation parameters of AutomA and 100 kV, matrix size of 512 512, field of view of 25 cm, slice thickness of 0.625 mm, helical pitch of 0.984:1, and isotropic voxel size of 0.625 mm. A total of 60 mL of contrast material followed by 30 mL of saline solution was injected into the antecubital vein at a rate of 4.5 mL/s with a power injection platform (Ulrich Tennessee XD2003 [Ulrich GmbH & Co. KG,
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Ulm, Germany]). The 3D-CTA data were recorded as Digital Imaging and Communications in Medicine files and transferred to a workstation (GE AW 4.5 [GE Healthcare]) equipped with software developed in-house by Capital Medical University to create stereolithography files containing blood vessel luminal surface data. These stereolithography files were then imported into ICEM CFD software (ANSYS Inc., Canonsburg, Pennsylvania, USA) to create 2.5 million finite-volume tetrahedral element grids with 3 prism layer elements for CFD simulations. CFX 14.0 software (ANSYS Inc.) was then used to solve the flow-governing NavierStokes equations with the assumption of laminar, incompressible, and Newtonian blood flow. The density and dynamic viscosity of the blood were set at 1060 kg/m3 and 0.004 N$s/m2, respectively. The blood vessel wall was assumed to be rigid with no-slip boundary conditions. The pulsatile velocity profile obtained by transcranial Doppler from a normal subject was applied for the inflow boundary conditions. Three cardiac cycle simulations were performed for numerical stability, and the last cardiac cycle was collected as output.
Definition of Rupture Point During microsurgical clipping or via intraoperative videos, the rupture point was detected as a point of tight adhesion of the thin, disrupted aneurysmal wall of a hematoma or white thrombus.18 Three independent neurosurgeons evaluated the operation videos with definition. The aneurysm 3D images could be transferred to the same angle and coordination according to the 2-dimensional video. Each neurosurgeon then determined each location of the rupture point on the patient-specific geometry model used to perform the CFD simulation. An area with the same size of the hematoma or white thrombus was marked by a circle point. In fact, the rupture point is not a real point, but an area. It is an incomplete aneurysm wall with the adhesion of the sludged blood. Apparent differences in assessment of the rupture point were resolved by consensus; if consensus could not be reached, the cases were excluded from the study. For each aneurysm, the neck width and aneurysm size were measured from the 3D-CTA image, and the aspect ratio (aneurysm size/ neck width) was calculated accordingly.
Hemodynamic Parameters and Data Analysis The hemodynamic characteristics at the rupture point and the whole aneurysm dome were calculated for comparison. The time-averaged WSS was measured in each region. The OSI was calculated to investigate the changes in the WSS vector within the cardiac cycle. The intra-aneurysmal flow structure was also evaluated to determine the flow impingement, and the contour of velocity was depicted on a cutting plane. Statistical analysis of the parameters at each region was performed using a paired Student t test. Pearson correlation coefficients were calculated between the morphologic parameters and the hemodynamic variables at both the rupture point and the aneurysm dome. Statistical significance was considered present at P < 0.05.
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RESULTS Of all included patients, 31.3% were men. The average age was 52.6 years (range, 36e68 years). Because of easier exposure and more indication for microsurgical clipping, 87.5% of the aneurysms were located at the middle cerebral artery (14/16). Eleven patients had Hunt-Hess grade 2, 3 patients had grade 3, and 2 patients had grade 4. The mean aneurysm size was 6.9 mm (range, 2.7e20.0 mm), and the mean aneurysm neck was 4.7 mm (range, 2.0e8.0 mm). The mean aspect ratio was 1.5. Three patients had multiple aneurysms, and 50% of the aneurysms were irregular in shape with daughter blebs. Of these cases with daughter blebs, the rupture points were confirmed at the blebs in 6 cases. Two cases did not show association between the blebs and rupture point. The rupture point is near to the turning of the blood inflow tract. The patient demographics and morphology of the aneurysms are shown in Table 1. The hemodynamics results of the 16 included aneurysms are shown in Table 2. The time-averaged WSS was 3.4855 3.8881 Pa at the aneurysm sac, which was significantly larger than that at the rupture point (1.5403 2.3688 Pa, P ¼ 0.002) (Table 3). The OSI at the sac and rupture point was also calculated. The OSI at the rupture point (0.0354 0.0459) was larger than at the sac (0.0220 0.0232). However, the difference was not significant (P ¼ 0.286) (Table 3). The hemodynamics findings in case 1 are shown in Figure 1. The intra-aneurysmal flow streamlines showed that 13 aneurysms (81.3%) had a complex flow pattern with more than 1 vortex
flow structure. On the cutting planes, only 5 cases (31.3%) showed a concentrated flow impact near the region of the rupture point. Most (68.7%) of the rupture points did not show direct flow impact with lower WSS. Pearson correlation analysis was performed between the morphologic and hemodynamic parameters. However, no significant correlation was found between these parameters.
DISCUSSION In this study, we evaluated a series of ruptured aneurysms in which the rupture points were confirmed during microsurgical clipping and used CFD to evaluate the hemodynamic characteristics at the rupture point. According to our results, the rupture point was associated with a lower WSS than at the aneurysm sac. The rupture point was confirmed as located at the daughter bleb in 75% of cases. To our knowledge, this is the largest case series to reveal the detailed hemodynamic characteristics around the rupture point. The hemodynamic characteristics associated with aneurysm rupture have been widely studied. However, the results are controversial.8,9,19,20 A CFD study by Cebral et al.19 showed that ruptured aneurysms were more likely to have a larger maximum WSS. However, Xiang et al.8 reported that low WSS was a risk factor for aneurysm rupture. Hemodynamic studies using preruptured aneurysm models also showed that low WSS was a risk factor for aneurysm rupture.9,11 All of these results demonstrate the hemodynamic features of the whole aneurysm sac
Table 1. Summary of Patient Demographics and Morphology Case Number
Age (Years)
Site
Smoke
Drink
HTN
DM
Hunt-Hess Grade
Multiple Aneurysms
Aneurysm Shape
Size (mm)
Neck (mm)
AR
1
56e60
RMCA
Yes
No
Yes
Yes
2
No
I
10
5
2.00
2
46e50
LMCA
No
No
Yes
No
2
No
R
4.8
2.7
1.78
3
66e70
RMCA
No
Yes
No
No
2
No
I
6
7
0.86
4
60e65
LMCA
No
No
No
No
2
No
R
7.2
5.5
1.31
5
50e55
RMCA
No
No
Yes
No
2
No
R
4.2
2.3
1.83
6
50e55
RMCA
No
No
No
No
3
No
R
2.7
2.2
1.23
7
36e40
RICA-Bifur
No
No
No
No
2
Yes
R
3
3
1.00
8
36e40
RMCA
No
No
No
No
2
No
R
4
3.5
1.14
9
50e55
LMCA
No
No
No
Yes
4
No
R
5
3
1.67
10
66e70
RMCA
No
No
No
Yes
2
No
I
6.5
5.5
1.18
11
40e45
RMCA
No
No
Yes
No
2
No
I
5
2
2.50
12
60e65
LMCA
No
No
Yes
No
4
No
I
12
8
1.50
13
60e65
RMCA
No
No
Yes
No
3
No
I
20
8
2.50
14
40e45
LMCA
No
No
No
Yes
3
No
R
5.6
4.2
1.33
15
40e45
ACOM
No
No
Yes
Yes
2
Yes
I
7.2
5
1.44
16
50e55
RMCA
No
No
Yes
Yes
2
Yes
I
7.5
7.5
1.00
HTN, hypertension; DM, diabetes mellitus; AR, aspect ratio; RMCA, right middle cerebral artery; I, irregular; LMCA, left middle cerebral artery; R, regular; RICA-Bifur, right internal carotid artery bifurcation; ACOM, anterior communicating artery.
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Table 2. Summary of Hemodynamic Results Case Number
aTAWSS (Pa)
aOSI
rTAWSS (Pa)
rOSI
Flow Pattern
Impact on RP
1
1.2968
0.0183
0.6616
0.0058
C
No
2
1.5186
0.0072
0.3159
0.0455
S
Yes
3
0.5284
0.0343
0.0752
0.0537
C
No
4
1.8796
0.0703
1.3948
0.0000
C
No
5
4.5156
0.0033
1.8986
0.0157
S
Yes
6
1.1701
0.0099
0.1237
0.0043
C
No
7
0.7996
0.0787
0.1399
0.0203
C
No
8
0.5943
0.0292
0.0005
0.1782
C
No
9
0.4397
0.0381
0.0011
0.1029
C
No
10
3.3722
0.0046
1.4934
0.0148
C
No
11
8.0132
0.0087
1.8149
0.0124
C
Yes
12
10.3241
0.0075
7.8421
0.0135
C
Yes
13
0.7216
0.0016
0.5180
0.0127
C
Yes
14
12.3071
0.0156
6.8720
0.0315
S
No
15
7.4533
0.0084
1.1788
0.0115
C
No
16
0.8344
0.0164
0.3142
0.0442
C
No
aTAWSS, time-averaged wall shear stress at the aneurysm dome; aOSI, oscillatory shear index at the aneurysm dome; rTAWSS, time-averaged wall shear stress at the rupture point; rOSI, oscillatory shear index at the rupture point; RP, rupture point; C, complex flow pattern; S, simple flow pattern.
without knowing the location of the rupture point. Therefore, the detailed and accurate hemodynamic characteristics of the rupture point were unknown in those studies, which might contribute to the controversial results. Therefore, the hemodynamic characteristics at the rupture point have been less thoroughly studied and are needed. To our knowledge, only a total of 30 cases from 6 studies, including single case reports, have been analyzed with respect to the hemodynamics at the rupture point based on different inspection methods of the rupture point.17 However, the findings remain controversial, and one of the reasons might be the different inspection methods of the rupture point. Of these 6 studies, only 2 were based on the microsurgical inspection of the rupture point, which might be more accurate. Cebral et al.12 reported 9 cases in which the rupture point was inspected in volume-rendered 3D images without surgical confirmation. Their results showed that the rupture point in 8 of 9 aneurysms (89%) had thinner and stiffer walls in regions of abnormally high WSS. Fukazawa et al.13 and Omodaka et al.16 reported 12 and 6 cases, respectively. The rupture point was confirmed during surgical clipping in both studies. Low WSS was revealed at the rupture point in both studies. Similar results were found in the present series, and the rupture point showed lower WSS than the aneurysm sac. The OSI at the rupture point was higher than that at the sac; however, the difference was not statistically significant. WSS is one of the most thoroughly evaluated parameters in hemodynamic studies and is thought to play an important role in aneurysm rupture.8,9,17,19 WSS is the frictional force of viscous
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blood on endothelial cells and can modulate the cellular functions of the vessel wall.8,21 Low WSS can increase endothelial permeability and promote inflammatory cell infiltration.22,23 Such a remodeling process may lead to further rupture.24,25 This study has several limitations. First, the retrospective study design and sample size may have introduced bias. Further studies with larger sample sizes are needed to investigate the hemodynamic characteristics of the rupture point, and bias from the statistical analysis with such a small sample size may be solved in the future. Second, in addition to hemodynamic factors, other pathophysiologic factors may have also been involved in the rupture mechanism. Finally, some of the assumptions used in the simulations, such as a rigid wall, laminar flow, and Newtonian blood flow, might have also introduced bias. CONCLUSIONS We have presented a series of cases in which the rupture point was identified during surgical clipping. The hemodynamic Table 3. Comparisons for Hemodynamic Parameters Examined Between Rupture Point and Aneurysm Dome Parameters
Rupture Point
Aneurysm Dome
P Value
TAWSS (Pa)
1.5403 2.3688
3.4855 3.8881
0.002
OSI
0.0354 0.0459
0.0220 0.0232
0.286
Values are mean SD or as otherwise indicated. TAWSS, time-averaged wall shear stress; OSI, oscillatory shear index.
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HEMODYNAMICS ON RUPTURE POINTS
Figure 1. Wall shear stress distribution (A), oscillatory shear index (B), flow impingement (C), and streamlines (D) of case 1. The rupture point was detected via intraoperative video (E). Arrows show the rupture point. Low
characteristics at the rupture point were different from the aneurysm sac, and the WSS was significantly lower at the rupture
2. Juvela S, Poussa K, Lehto H, Porras M. Natural history of unruptured intracranial aneurysms: a long-term follow-up study. Stroke. 2013;44: 2414-2421. 3. Dhar S, Tremmel M, Mocco J, Kim M, Yamamoto J, Siddiqui AH, et al. Morphology parameters for intracranial aneurysm rupture risk assessment. Neurosurgery. 2008;63:185-196 [discussion: 196-197]. 4. Liu J, Xiang J, Zhang Y, Wang Y, Li H, Meng H, et al. Morphologic and hemodynamic analysis of
point. Further study on the rupture risk assessment is still needed with more data and detailed information.
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Conflict of interest statement: This work was supported by the National Key Research Development Program (2016YFC1300800), the National Natural Science Foundation of China (816705049, 81371315, 81471167, and 81220108007), and the Special Research Project for Capital Health Development (2018-4-1077).
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Received 10 April 2018; accepted 3 July 2018
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24. Pentimalli L, Modesti A, Vignati A, Marchese E, Albanese A, Di Rocco F, et al. Role of apoptosis in
Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.07.026
Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.07.026