Article Text


Original research
Impact of the global outflow angle on recanalization after endovascular treatment of middle cerebral artery bifurcation aneurysms
  1. Yannick de La Torre1,
  2. Stéphane Velasco1,
  3. Jean-Pierre Tasu1,
  4. Cassandre Wanpouille1,
  5. Paul Chan1,
  6. Raphael Velasco2,
  7. Guillaume Sztark3,
  8. Pierre Ingrand4,
  9. Samy Boucebci1
  1. 1 Department of Radiology, CHU of Poitiers, Poitiers, Vienne, France
  2. 2 Laboratoire Des Technologies Innovantes, University of Picardie Jules Vernes, Amiens, France
  3. 3 Department of Radiology, Hospital Center of Angoulême, Angoulême, France
  4. 4 Department of Biostatics, Faculty of Medecine, University of Poitiers, Poitiers, France
  1. Correspondence to Dr Yannick de La Torre, Department of Radiology, CHU of Poitiers, 86 000 Poitiers, France; yannick.delatorre{at}


Background and purpose Intracranial aneurysm recanalization after endovascular treatment (EVT) remains a major problem. The goal of this study was to find new predictive factors of recanalization after EVT of middle cerebral artery (MCA) bifurcation aneurysms.

Methods 96 MCA bifurcationaneurysms, ruptured or unruptured, treated by EVT between Septembre 2009 and December 2014, were retrospectively included. Clinical parameters and aneurysm characteristics were recorded. From the initial three-dimensional DSA, spatial coordinates found on parent and daughter arteries of MCA bifurcations gave four different flow angle values; inflow, outflows 1 and 2, and the global outflow angle (the sum of the two outflow angles). Inter- and intra-observer reproducibilities of three-dimensional angle value measurements were performed.

Results Recanalization occurred in 25 cases (26%) and retreatment was performed in 11 cases (11%). Only 1 patient (1%) had rebleeding. Univariate analysis established the following as predictive factors of recanalization: high blood pressure (P=0.014), aneurysm height (P<0.001), aneurysm width (P<0.001), neck size (P<0.001), postoperative occlusion class (P=0.040), percentage of packing volume (P<0.001), as well as the two outflow angles (P=0.006 and 0.045), and the global outflow angle (P<0.001). Multivariate analysis revealed two independent risk factors for recanalization: the global outflow angle (OR=1.05; 95% CI 1.02 to 1.08; P<0.002) and aneurysm width (OR=0.67; 95% CI 0.46 to 0.96; P=0.031). A global outflow angle threshold <192° was found to be a risk factor for recanalization (OR=13.75; 95% CI 4.46 to 42.44), with a sensitivity of 80% and specificity of 77%.

Conclusions This study emphasizes that a new parameter, the global outflow angle, can be predictive of recanalization for MCA bifurcation aneurysms treated by EVT.

  • aneurysm
  • blood flow
  • hemorrhage
  • magnetic resonance angiography
  • subarachnoid

Statistics from


Spontaneous rupture remains the major complication of intracranial aneurysm, with an annual risk estimated at approximately 0.7–1.9% per year.1 Hemodynamic factors seem to play a key role in intracranial aneurysm initiation2; the vessel wall is exposed to the highest wall shear stress (WSS) and WSS gradient at the apex of the arterial bifurcations, the most frequent location of intracranial aneurysms.3 This might explain why middle cerebral artery (MCA) bifurcation is one of the most common sites of intracranial aneurysms.4 Endovascular treatment (EVT) has become the gold standard for ruptured and unruptured intracranial aneurysms since the International Subarachnoid Aneurysm Trial (ISAT) study.5 However, a meta-analysis observed a 20.8% rate of recanalization of coiled aneurysms.6

Several factors affecting the onset of recanalization have already been published; aneurysm size (height >8 mm or ≥10 mm),7 8 neck size >4 mm,8 9 postoperative occlusion class,9 10 packing density,11 rupture status of the aneurysm,9 12 young age,13 and duration of follow-up after treatment.9 It has also been shown that the inflow angle (IA) plays a discriminant role in rupture status for sidewall cerebral aneurysms14 : a high IA value results in higher inflow velocity and greater WSS in both inflow zone and aneurysmal dome. Morphological factors therefore seem to play a central role in the recanalization process15 16 but these parameters have not been fully studied, particularly with a three-dimensional (3D) approach.

We studied the global outflow angle (GOA), which is the sum of the two outflow angles between the parent M1 artery and the two daughter M2 arteries (M2a and M2b). Our main objective was to assess the GOA, using a 3D approach, as a new predictive factor of aneurysm recanalization after EVT.

Materials and methods

Patients and treatment

The research was conducted according to the principles of the Declaration of Helsinki. Considering the retrospective design of the study, local institutional review board approval was not required.

In a retrospective monocentric study, all patients treated by an endovascular approach for ruptured or unruptured MCA bifurcation aneurysms, between September 2009 and December 2014, were included. Exclusion criteria were: dissecting or fusiform aneurysms, aneurysms associated with a brain arteriovenous malformation, MCA trifurcations, missing initial 3D DSA, early death after therapy or any causes of lack of follow-up, and aneurysms treated by distal occlusion of the M1.

All treatment procedures were done under general anesthesia. Systemic heparin and aspirin were administered as often as possible. The aim of coil embolization was to pack the aneurysm as densely as possible. Immediate postoperative aneurysm occlusion was evaluated using the Raymond–Roy Occlusion Classification (RROC).17 Packing density was assessed by calculating the percentage of packing volume of the aneurysm, using the AngioCalc application, available online (

For each patient, clinical data (gender, age, smoking status, hypertension, diabetes, and rupture status of the aneurysm) were extracted from their archived files and/or computerized medical records. The following anatomic parameters of the aneurysm were also reported; aneurysm size (height and width), height/width ratio, neck size, aspect ratio (height to neck ratio) and presence or not of an M1 temporal precocious branch.

Imaging follow-up

Before treatment, DSA, including frontal and lateral views, 3D rotational angiography, and a working view, were acquired on a biplane Axiom Artis dBA angiography system (Siemens AG, Healthcare Sector, Forchheim, Germany). After EVT, follow-up was performed by DSA and MR angiography (MRA) according to the French guidelines of the Neurosurgery Society ( MRA was acquired on a General Electric 1.5 T (Optima Mr 450W, Milwaukee, USA) and/or a Siemens 3T Verio (B17 version, Nuremberg, Germany). Three-dimensional time of flight (3D-TOF) was used to explore the Willis polygon arteries, without contrast administration. DSA during follow-up included a working view determined from the pretreatment acquisition, and frontal and lateral views. Three-dimensional acquisition was performed on demand in cases of doubt.

Imaging analysis

All MRA and DSA angiograms performed during the follow-up period were reviewed specifically for this study in consensus of a junior and a senior interventional neuroradiologist (3 and 15 years of experience, respectively), blind to all clinical data and follow-up data. The delay between treatment and first recanalization was noted. For each control, EVT was classified according to RROC. Retreatment was performed as soon as the remnant was found to be significant.

From the initial DSA, measurements of aneurysm anatomic factors and angles were performed on a dedicated work station using OsiriX software (V.3.9.4, Pixmeo Sarl, Geneva, Switzerland). Bifurcation angles were measured from 3D coordinates (x, y, z) of key points placed on the parent (M1) and daughter (M2) arteries of the MCA bifurcations. Figure 1 illustrates the measurements. Three-dimensional formula of scalar product (see online supplementary data) gave 3D angle values. IA was defined according to Baharoglu et al.14 The following angles were also measured: (1) angle between the parent M1 artery and the largest daughter M2 artery (M2a), termed outflow angle 1 or OA 1 (also called in the literature lateral angle 118 or angle A19); and (2) angle between the parent M1 artery and the smallest daughter M2 artery, termed outflow angle 2 or OA 2 (also called in the literature lateral angle 218 or angle B19). The sum of these two angle values was defined as the GOA.

Supplementary file 1

Figure 1

Method of measurement of an outflow angle 1 (middle cerebral artery bifurcation aneurysm). (A) Axis of flow on M1. (B, C) Tangent lines of initial orientations of M2a and M2b. (D) Three-dimensional coordinates of the three points needed to measure the outflow angle 1; point B was placed on the line (axis of flow) passing through the middle of the distal parent M1 vessel; point C was on the tangent line of the initial orientation of each daughter M2 artery (passing through the middle of the artery); point A was at the intersection of the two previous lines.

GOA and IA intra- and inter-observer reproducibilities were studied by measuring, twice, 30 aneurysms chosen at random.

Statistical analysis

Statistical analyses were performed with SAS Software. The significance level alpha was 5% (P<0.05). The Wilcoxon two sample test was used to evaluate non-parametric data (ie, aneurysm anatomic factors, angle measurements, percentage of packing volume, and follow-up time). Mean, median, and SD were performed for these parameters. Fisher’s exact test was used to evaluate parametric data (ie, gender, risk factors for atherosclerosis, aneurysm status (ruptured or not), presence of M1 temporal precocious branch, postoperative occlusion class, and complications of treatment and/or related to the natural history of subarachnoid hemorrhage (SAH)). Univariate analysis was first performed, and then a multivariate analysis with logistic regression variables was carried out. Receiver operator characteristic (ROC) curves were performed to determine area under the curve (AUC) index as well as cut-off values for significant parameters.

Intra- and interobserver reproducibility was studied using the Bland–Altman plot method.


Patient characteristics

A total of 120 patients were treated for MCA aneurysm by EVT during the inclusion period. Twenty-four patients were excluded. Figure 2 gives the flowchart of the study. Hence patients were included in the study, 64 women (67%) and 32 men (33%), with a mean age of 52 years (range 24–76). High blood pressure was observed in 33 patients (34%), smoking status in 35 (36%), and alcohol abuse in 8 (8%); there were no cases of diabetes.

Figure 2

Flowchart of the study. Exclusions were due to dissecting aneurysm (1 patient), aneurysm associated with a brain arteriovenous malformation (1 patient), middle cerebral artery (MCA) trifurcation (2 patients), missing initial three-dimensional DSA (4 patients), early death after subarachnoid hemorrhage (10 patients), lack of follow-up (5 patients), and aneurysm treated by distal occlusion of the M1 (1 patient).

Table 1 shows the aneurysm characteristics. Ninety patients (94%) were treated by coiling, with a remodeling technique using balloons when needed. One patient (1%) was treated with a stent assisted coiling technique, 4 (4%) by Woven EndoBridge (WEB) device (unruptured aneurysms), and 1 (1%) by WEB device and intracranial stenting.

Table 1

Aneurysm characteristics

After the procedure, complete occlusion (class I of the RROC) was obtained in 39 patients (41%). There was a residual neck (class II of the RROC) in 49 patients (51%), and a residual aneurysm (class III of the RROC) in 8 patients (8%). Mean±SD percentage of packing volume of all coiled aneurysms was 50%±31%. Periprocedural and SAH complication rates showed 9 bleeding complications (9%), 12 hydrocephalus (13%) and 15 vasospasms (16%). Nineteen thromboembolic complications were recorded (20%).

Follow-up and recanalization rate

The average follow-up time after treatment was 30 months (median delay of 24 months). At least one 3D-TOF-MRA was available for all patients. Sixty-eight patients (71%) had at least one conventional cerebral angiogram during the follow-up period. During this screening, recanalization occurred in 25 aneurysms (26%). Among recanalized aneurysms, 7 were grade II (28%) and 18 were grade III (72%). The average time between treatment and detection of recanalization was 14 months. Retreatment was performed in 11 patients (11% of all aneurysms studied, 44% among recanalized aneurysms). Two patients were retreated by surgery alone, one patient by surgery and coiling remodeling, three patients by coiling remodeling alone, four patients by coiling remodeling and intracranial stenting, and one patient by intracranial stenting alone. Four of these patients needed a second retreatment. The average time between the first treatment and retreatment was 15 months. Only one patient (1%) had intracranial bleeding during follow-up.

Factors affecting recanalization

Table 2 gives the main results of the univariate and multivariate analyses.

Table 2

Results of univariate and multivariate analyses

In the univariate analysis, there were no significant differences between age or clinical factors and the onset of recanalization, except for high blood pressure (P=0.014). There were more ruptured aneurysms in the recanalization group (18 ruptured and 7 unruptured), but this was not significant (P=0.157). Height, width, and neck size of the aneurysm were statistically different between the recanalized and non-recanalized aneurysms (P<0.001 for all of these parameters). There was no statistically significant difference for aspect ratio (P=0.245), height/width ratio (P=0.220), or the presence of M1 temporal precocious branch (P=0.482). Postoperative occlusion class was correlated with recanalization (P=0.040). Packing density, estimated with the help of the AngioCalc application, was also linked to recanalization; the percentage of packing volume was 29.4±19.1% in the recanalization group versus 56.0%±31.0% in non-recanalization group (P<0.001). There were no significant differences in the onset of periprocedural and SAH complications between the two groups, or in length of follow-up.

IA was not statistically linked to recanalization; mean±SD IA was 154.1±22.0° in the recanalization group versus 151.1±19.9° in the non-recanalization group (P=0.245). On the other hand, outflow angles 1 and 2, as well as GOA were statistically linked to recanalization. Mean angle values for these three parameters were lower in the recanalization group. Mean GOA was 169.8±32.6° in the recanalization group versus 211.5±26.1° in non-recanalization group (P<0.001). IA–GOA value also differed between the two groups (P<0.001).

According to the univariate analysis, the following parameters were introduced into the multivariate analysis: height, width, neck size, outflow angle 1, outflow angle 2, GOA, and IA−GOA (see table 2). In order to homogenize the population, percentage of packing volume was not included in the multivariate analysis because five patients were not treated with a coiling procedure. According to the multivariate analysis, two factors were significantly associated with the onset of recanalization: GOA (OR=1.05; 95% CI 1.02 to 1.08; P<0.002) and width of the aneurysm (OR=0.67; 95% CI 0.46 to 0.96; P=0.031). A GOA threshold <192° gave a sensitivity of 80% and specificity of 77% for recanalization. For this value, OR was 13.75 (95% CI 4.46 to 42.44). AUC value was 0.8518 (SD=0.05). Among the 26 patients in the recanalization group, 21 had a GOA <192°. Percentage of packing volume threshold <38% gave a sensitivity of 86% and specificity of 75% for aneurysm recanalization. For this value, OR was 19.37 (95% CI, 5.10 to 73.62). AUC value was 0.8340 (SD=0.05).

Intra- and inter-observer reproducibility of measuring angles in three dimensions

For intraobserver reproducibility, the mean difference in calculating GOA was 4° (SD bias=7°; 95% limits of agreement −9° to 17°). For inter-observer reproducibility, the mean difference in calculating GOA was 6° (SD bias=8°; 95% limits of agreement −9° to 21°).


According to our results, GOA seems to be an excellent predictive parameter of aneurysm recanalization after EVT; a lower GOA value was associated with more frequent recanalization.

Our cohort seems to be similar to other published cohorts, reporting recanalization rates of 26%,9 20 retreatment rates of 11%,21 and rebleeding rates of 1%.21

In agreement with the literature, aneurysm size,7 8 neck size,8 9 postoperative occlusion class,9 10 and packing density11 were correlated with the onset of recanalization. The Clinical and Anatomic Results in the Treatment of Ruptured Intracranial Aneurysms (CLARITY) study7 has also demonstrated a link between hypertension and recanalization. Previous studies have shown that high packing densities could prevent aneurysm recurrence.11 Using the AngioCalc application seems to be more reproducible in calculating the percentage of packing volume than subjectively assessing angiographic occlusion,22 and the threshold value of 36% found here could be considered as a risk factor for recanalization in MCA bifurcation aneurysms (sensitivity of 86% and specificity of 75%). However, further studies are required to evaluate this parameter, which was not included in the multivariate analysis.

This study introduces a new predictive factor for recanalization: GOA. It was the only parameter, along with the width of the aneurysm, that was significantly linked to recanalization in the multivariate analysis. Many intracranial aneurysms develop at arterial bifurcations, where WSS and turbulences are higher.3 These hemodynamic conditions are not deeply modified after treatment, and high WSS and high blood flow velocity are systematically observed near the remnant neck of partially embolized aneurysms.23 As GOA seems to be an independent risk factor for recanalization, it could play a leading role in the periprocedural management of these aneurysms. More aggressive initial treatment should likely be performed for patients with sharper bifurcation angles in order to avoid recanalization. This could involve all techniques that lead to the highest packing density (and in particular in the neck area) and/or the use of intracranial stenting. Follow-up of these patients might also be closer for the purpose of earlier detection of the onset of recanalization, and to prevent rebleeding.

This study has some limitations: (1) this was a monocentric study with a retrospective design; the imaging protocol differed for some patients, who underwent 3D-TOF-MRA follow-up in both 1.5 T and 3 T MRA. It is well known that 3D-TOF-MRA at 3 T is superior to 1.5 T for evaluation of treated aneurysms.24 In the same way, the follow-up protocol was modified during the analyzed period, in accordance with the 2011 guidelines of the French Society of Neurosurgery; (2) the number of patients was limited; and (3) lastly and most importantly, we did not evaluate the postoperative remodeling of MCA bifurcation. MCA bifurcation angles might not be the same before and after EVT25 and that could play a role in the recanalization process, particularly because of hemodynamic changes at the bifurcation apex. We did not perform 3D DSA after treatment to limit X-ray exposure, and in accordance with the guidelines. A further prospective study including more patients and evaluating the potential modifications of GOA after EVT should be performed.


This study emphasizes the concept that angle values between arteries of the MCA bifurcation could be a predictive factor of aneurysm recanalization after EVT. Sharper bifurcation angles between the parent M1 artery and the two daughter M2 arteries results in a lower GOA, and hence more frequent recanalization. A GOA threshold value <192° could be considered as a risk factor for recanalization for MCA bifurcation aneurysms treated by an endovascular approach, with a sensitivity of 80% and specificity of 77%.


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  • Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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