morphological risk factors for rupture of small (

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Morphological Risk Factors for Rupture of Small (


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Morphological Risk Factors for Rupture of Small (


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Abstract

Background: The management of small unruptured intracranial aneurysms is still

controversial. Given the distinctive natural history of aneurysm at different locations,

location-specific analysis might be a reasonable approach. This study aimed to

investigate morphological discriminators for rupture status by focusing on only

posterior communicating artery (PcomA) aneurysms smaller than 7 mm.

Methods: In 108 small PcomA aneurysms (68 ruptured, 40 unruptured), clinical and

morphological characteristics were compared between the ruptured and unruptured

groups. Multivariate logistic regression analysis was performed to determine the

independent predictors for the rupture status of small PcomA aneurysms.

Results: None of the clinical characteristics were significantly different between the

ruptured and unruptured group (P>0.05). The ruptured group revealed a significantly

larger size (P=0.009), aspect ratio (P=0.009), size ratio (P=0.002), dome-to-neck ratio

(P=0.002), inflow angle (P


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Introduction

Unruptured intracranial aneurysms (IAs) are increasingly detected, and the

majority of them are small16,22

. Although the International Study of Unruptured

Intracranial Aneurysms (ISUIA) trial reported that the rupture rate of unruptured IAs

smaller than 7 mm is very low23

, a recent prospective Finnish cohort study showed

that 25% of the patients with small (


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de-identified prior to analysis.

Patients and Clinical Characteristics

We retrospectively reviewed a total of 135 consecutive patients diagnosed with

PcomA aneurysms between January 2014 and June 2015 at Changhai Hospital. All the

PcomA aneurysms were determined and measured using three-dimensional rotational

angiography (3DRA). After exclusion of patients with multiple aneurysms and

PcomA aneurysms larger than 7 mm, 108 PcomA aneurysms were included in the

study. Of these PcomA aneurysms, 68 were ruptured with a history of SAH and 40

were unruptured. For the 40 patients in the unruptured group, 14 presented with mild

headache or dizziness, 7 suffered from ischemic events, 8 presented with symptoms of

oculomotor nerve palsy, and the other 11 aneurysms were detected incidentally

without symptoms of cerebrovascular diseases. The clinical characteristics were

collected as the following: age, gender, hypertension, diabetes mellitus, current

smoking status, history of familial SAH, and presence of homolateral oculomotor

nerve palsy. Hypertension was defined as taking antihypertensive agents, a systolic

blood pressure of ≥140 mmHg, or a diastolic blood pressure of ≥90 mmHg. Diabetes

mellitus was defined as taking antidiabetic agents, treatment with insulin injections, a

fasting plasma glucose level of ≥ 126 mg/dl, a random plasma glucose level of > 200

mg/dl, or a hemoglobin A1c level of ≥ 6.5%. Current smoker was defined as those

who had smoked at least 100 cigarettes during their lifetime and reported smoking

every day or some days before being admitted.

Radiological Findings and Morphological Calculations

The 3DRA was performed using the Artis zee Biplane angiographic system

(Siemens, VC14, Germany). All of the acquired 3DRA data were transferred to the


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syngo X Workplace (Siemens, VB15, Germany) for reconstruction of the 3D internal

carotid artery vessel tree and exported in a stereolithography (STL) format to

GEOMAGIC STUDIO 9.0 software (Geomagic, Morrisville, North Carolina). Firstly,

we defined the neck plane as the location where the aneurysmal sac pouched outward

from the parent vessel. After that, the models were divided into the aneurysm dome

and the inlet and outlet planes of the parent artery, and then exported in STL formats.

These formats were imported into Matlab 7.0 (The MathWorks, Inc., Natick, MA,

USA), which was used to calculate and visualize the morphological parameters.

Through the above process, we could obtain the morphological parameters of the

PcomA aneurysms as defined in previous studies4,25

(Figure 1). Size of aneurysm

dome was defined as the maximum diameter of the aneurysm dome. Dome height was

the longest dimension from the neck to the dome tip and dome width were measured

perpendicular to the dome height. Aspect ratio (AR) was computed by dividing dome

height by neck width. Size ratio (SR) was calculated by dividing size by the average

diameter of parent arteries and dome-to-neck ratio (DN) by dividing size by neck

width. Bottleneck factor (BN) was defined as the ratio of dome width to neck width.

Inflow angle was the angle between inflow and the aneurysm’s main axis from the

center of the neck to the tip of the dome. In addition, we evaluated the presence of

bleb formation on the aneurysms and whether the PcomA was fetal type. A fetal-type

PcomA was defined as a PcomA that has the same or larger caliber as the P2 segment

of the posterior cerebral artery, and is associated with an atrophic P1 segment.

Statistical Analysis

Statistical analyses were performed using Microsoft Excel 2003 and SAS

9.1(SAS Institute Inc., Cary, NC, USA). Variables were expressed as median


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(interquartile range), or number of patients (%) as appropriate. Mann-Whitney U-test

was used for measurement data and the chi-square test was performed for

cross-tabulation. The parameters found to be significant (P


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factors of small PcomA aneurysms rupture using a backward elimination process. All

the significant parameters that were significant in univariate analysis were included.

The result showed that SR (Odds ratio [OR]: 1.67; 95% confidence interval [CI]:

1.12-2.50; P=0.012) and inflow angle (OR: 2.01; 95%CI: 1.32-3.05; P=0.001) were

independently associated with the rupture status of small PcomA aneurysms (Table

2).

Discussion

With the wider availability of modern imaging techniques, patients with

unruptured IAs are increasingly detected, even with small asymptomatic ones16

.

Previous studies revealed that the size of IA was significantly correlated to their

rupture status, and the risk of unruptured IAs smaller than 7 mm was relatively low8,23

.

For small IAs in the anterior circulation, the predicted risk of rupture may be even

lower than the risk of treatment complications9. However, according to studies

depending on the locations, rupture of small anterior circulation aneurysms was the

main cause of aneurysmal SAH, which carries a high rate of mortality and

morbidity2,3,11,17

. As a result, clinical decision-making for small unruptured IAs is still

difficult for physicians, and reliable predictors for rupture risk are much needed.

Various attempts have been made to stratify the rupture risk of intracranial

aneurysms5,15

. Currently, several clinical, hemodynamic and morphological variables,

including familial SAH history, aneurysm size, and low wall shear stress (WSS), have

been consistently associated with an increased risk of aneurysm rupture8,22,24

.

However, these findings were obtained by analysis of a limited number of parameters

with a relatively small sample size. Furthermore, most of these studies were not


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location-specific. In fact, the proportion of small aneurysms and their risk of rupture

varies in different locations6,10

. The anatomic geometry, vessel wall thickness, and

blood flow pattern of IAs in different locations are distinctive. This might be the

reason why some findings are conflicting. As a result, location-specific studies may

be more likely to achieve accurate results.

Without considering location, IA size loses relevance to rupture risk 6,11

. In this

study, although the aneurysm size of the ruptured group was significantly larger than

that of the unruptured group, it was not retained as an independent risk factor that

discriminated the rupture status of PcomA aneurysms. The variability of the rupture

risk might be related to the caliber of the originating or parent vessel. SR, a parameter

firstly proposed by Dhar et al4, which incorporates the IA parent vessel geometry into

a morphological index, had been shown to be related with aneurysm rupture in some

previous studies12,14

. Kashiwazaki et al12

demonstrated that SR could accurately

predict the rupture risk of UIAs, especially small aneurysms (


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studies have confirmed the significant role of inflow angle in predicting aneurysm

rupture1,21

. In our study, increasing inflow angle was highly correlated with rupture

status of PcomA aneurysms. From the point of view of hemodynamics, increasing

inflow angle might result in higher inflow velocity and greater wall shear stress

magnitude and spatial gradients in the inflow zone and dome, as well as a greater

transmission of kinetic energy into the distal portion of the dome1. These

hemodynamic features might be important factors that increase the risk of rupture.

Most morphological studies of rupture risk, including the current one, are based

on the comparison between post-ruptured and unruptured aneurysms. We know that

the analysis of aneurysms in ‘pre-rupture’ status might be more accurate due to the

possible change of morphology after rupture. Several studies have reported some rare

cases with radiographic records not long before rupture5,19

. However, it is difficult to

capture the specific status clinically to gain a considerable sample size for accurate

statistical analysis. Therefore, currently, comparisons between post-ruptured and

unruptured IAs are used as an available alternative method, which could still provide

meaningful findings for clinicians to discriminate rupture status of IAs.

Limitations

In the current study, we identified SR and inflow angle as independent risk

factors for rupture of small PcomA aneurysms, which are convenient and quick

measurements for the clinical prediction of aneurysm rupture. The study does have

several limitations. Firstly, as a retrospect study, there was an inherent bias selection

of the PcomA aneurysms, especially as it did not include aneurysms larger than 7 mm.

In addition, the relatively small and unbalanced sample size of both groups might


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affect the analysis. Due to the limited sample size, we only used several most widely

studied parameters to ensure the reliability of the multivariate analysis. Finally,

morphology of the PcomA aneurysms might change after aneurysm rupture, which

could affect the accuracy of calculations.

Conclusions

This study showed that not only the aneurysm size, but also SR, AR, DN, inflow

angle and bleb formation were significantly different between ruptured and

unruptured small PcomA aneurysms. Most importantly, this is the first demonstration

that SR and inflow angle are independent factors for predicting the rupture risk of

small PcomA aneurysms.

Competing Interests

None.

Acknowledgement

We gratefully acknowledge the Shanghai Supercomputer Center for its helpful

provision of calculation software. This study received funding from National Natural

Science Foundation of China (No. 81571118 and No. 81301004) and Shanghai

Education Commission (No. 14ZZ081).


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Figure Legend

Figure 1. Definitions of Morphological Parameters. Size = Dmax; aspect ratio =

Height/Neck; size ratio = 6Dmax/(D1+D2+D3+D4+D5+D6); diameter of PcomA =

(D5+D6)/2; dome-to-neck ratio = Dmax/Neck; bottleneck factor=Width/Neck; inflow

angle=α.


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Table 1 Clinical and Morphological Characteristics of Small PcomA Aneurysms

Variables are expressed as median (interquartile range), or number of patients (%)

PcomA aneurysms

Variables Total (n=108) Ruptured (n=68) Unruptured (n=40) P Value

Clinical Characteristics

Age 60 (52, 66) 58 (51, 63) 62 (56, 67) 0.056

Male 24 (22.2) 13 (19.1) 11 (27.5) 0.312

Hypertension 53 (49.1) 31 (45.6) 22 (55.0) 0.345

Diabetes Mellitus 11 (10.2) 4 (5.9) 7 (17.5) 0.054

Current Smoking 17 (15.7) 9 (13.2) 8 (20.0) 0.351

Familial SAH 9 (8.3) 5 (7.4) 4 (10.0) 0.904

Oculomotor Nerve Palsy 18 (16.7) 10 (14.7) 8 (20.0) 0.476

Morphological Characteristics

Size, mm 4.36 (3.23, 5.47) 4.50 (3.60, 5.696) 3.92 (2.46, 4.72) 0.009

Diameter of PcomA 1.84 (1.27, 2.25) 1.80 (1.11, 2.18) 1.99 (1.53, 2.50) 0.302

Aspect Ratio (AR) 0.97 (0.75, 1.37) 1.08 (0.84, 1.37) 0.83 (0.66, 1.24) 0.009

Size Ratio (SR) 1.61 (1.20, 1.94) 1.72 (1.30, 2.09) 1.42 (0.90, 1.77) 0.002

Dome-to-Neck Ratio (DN) 1.08 (0.91, 1.41) 1.16 (0.96, 1.59) 0.97 (0.86, 1.22) 0.002

Bottleneck Factor (BN) 1.13 (0.94, 1.35) 1.18 (1.01, 1.38) 1.09 (0.90, 1.32) 0.154

Inflow Angle, ° 113 (98, 128) 119 (105, 132) 99 (89, 118)


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Table 2 Independent Risk Factors for Rupture of Small PcomA Aneurysms

Variables P Value Odds Ratio 95% Confidence Interval

Size Ratio (SR) 0.012 1.67 1.12-2.50

Inflow Angle 0.001 2.01 1.32-3.05


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Abbreviations list:

AR = aspect ratio

BN = bottleneck factor

CI = confidence interval

DN = dome-to-neck ratio

IA = intracranial aneurysm

OR = odds ratio

PcomA = posterior communicating artery

SAH = subarachnoid hemorrhage

SR = size ratio

STL = stereolithography

WSS = wall shear stress

3DRA = three-dimensional rotational angiography


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Disclosure- Conflict of Interest

We declare that the manuscript is original, has not been published before and is not

currently being considered for publication elsewhere. We wish to confirm that there

are no known conflicts of interest associated with this publication and there has been

no significant financial support for this work that could have influenced its outcome.

This manuscript has been read and approved by all named authors.

morphological risk factors for rupture of small (

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