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Hemorrhagic stroke
ORIGINAL RESEARCH
Assessment of intracranial aneurysm rupture based on morphology parameters and anatomical locations Yongtao Zheng,1 Feng Xu,1 Jinma Ren,2 Qiang Xu,3 Yingjun Liu,1 Yanlong Tian,1 Bing Leng1 1
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China 2 Center for Health Outcomes Research, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA 3 Department of Radiology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China Correspondence to Professor Bing Leng, Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, No 12 Wulumuqi Middle Road, Shanghai 200040, China; [email protected] YZ and FX contributed equally. Received 13 October 2015 Accepted 25 November 2015
ABSTRACT Objectives The aim of the present study was to identify image-based morphological parameters and anatomical locations associated with intracranial aneurysm (IA) rupture. Methods Nine morphological parameters and aneurysm location were evaluated in 150 patients with saccular IAs (82 unruptured, 68 ruptured) using threedimensional geometry. Aneurysm location and morphological parameters including size, aspect ratio, size ratio, height–width ratio, flow angle, aneurysm inclination angle, parent artery angle, vessel angle, and aneurysm shape were explored to identify a correlation with aneurysm rupture. These factors were analyzed using a two-tailed independent Student t test or the χ test for significance. Significant factors were further examined using logistic regression analysis. Additionally, receiver operating characteristic (ROC) analysis was performed to evaluate each parameter. Results Statistically significant differences were observed in ruptured and unruptured groups for aspect ratio, size ratio, height–width ratio, flow angle, aneurysm inclination angle, vessel angle, aneurysm shape, and aneurysm location. Logistic regression analysis further revealed that size ratio (OR 1.66; 95% CI 1.05 to 2.64), height–width ratio (OR 14.22; 95% CI 2.67 to 75.88), aneurysm inclination angle (OR 1.04; 95% CI 1.01 to 1.07), aneurysm shape (OR 4.68; 95% CI 2.44 to 8.98), and aneurysm location (OR 1.60; 95% CI 1.15 to 2.23) had the strongest independent correlation with ruptured IA. The ROC analysis showed that the size ratio and flow angle had the highest area under the curve, with values of 0.735 and 0.730, respectively. Conclusions Size ratio, height–width ratio, aneurysm inclination angle, aneurysm shape, and aneurysm location might be important for discriminating between ruptured and unruptured aneurysms. Further investigation will determine whether these morphological parameters and anatomical locations will be reliable predictors of aneurysm rupture.
INTRODUCTION
To cite: Zheng Y, Xu F, Ren J, et al. J NeuroIntervent Surg Published Online First: [please include Day Month Year] doi:10.1136/ neurintsurg-2015-012112
The annual incidence of subarachnoid hemorrhage resulting from the rupture of intracranial aneurysm (IA) is estimated at nine per 100 000 affected individuals.1 Even with the best available medical care, the majority of individuals with subarachnoid hemorrhage die or become severely disabled. Although an adequate treatment for IA is urgently needed, the postoperative morbidity and high treatment costs must be carefully considered for the
development of treatment strategies.2–4 The rupture rate of IA is significantly lower than the incidence rate. Indeed, IA affects approximately 2–5% of the entire population,5 but only 1–3% of all IAs actually rupture.6 7 Recently, Greving et al8 summarized the results of six prospective studies, reporting an average observed 1-year risk of aneurysm rupture of 1.4% and a 5-year risk of 3.4%. Thus, most IAs do not require clinical intervention. However, reliable knowledge about the risks of IA rupture in different populations will facilitate the development of planning, screening, and prevention strategies and will provide information for the prognosis of individual patients. The most ubiquitous parameter is IA size. Although aneurysms exceeding 7 or 10 mm in size are considered to be dangerous, several studies have shown that a large percentage of ruptured aneurysms are, in fact, smaller than 7 mm.9–12 The relationship between rupture risk and IA size has not been completely elucidated. Interestingly, Ujiie et al13 reported that the aspect ratio (AR) might be useful in predicting imminent aneurysmal rupture, while Dhar et al14 reported that the size ratio (SR) and aneurysm angle were meaningful morphological metrics for the assessment of rupture risk. Consistent with previous studies, we reported the importance of several morphological parameters and intracranial locations for IA rupture.
MATERIALS AND METHODS Patient population Between January 2013 and December 2014, threedimensional rotational digital subtraction angiography (DSA) images (Philips Allua Xper, The Netherlands) were obtained from patients with saccular terminal or sidewall IA treated at Huashan Hospital. One hundred and fifty consecutive patients with 82 unruptured and 68 ruptured aneurysms met these criteria. Once diagnosed as IA, DSA was performed in all patients in our hospital who were randomly enrolled in the study. Of the 150 saccular aneurysms, 125 were sidewall type and 25 were terminal type. Patients with multiple aneurysms were classified according to the size and location of the largest aneurysm observed.
Definition of parameters Nine morphology parameters and aneurysm location were defined in our study. All morphology parameters were evaluated by two neurosurgeons (FX, BL) and one radiology physician (QX) (figure 1).
Zheng Y, et al. J NeuroIntervent Surg 2016;0:1–7. doi:10.1136/neurintsurg-2015-012112
1
Downloaded from http://jnis.bmj.com/ on January 17, 2016 - Published by group.bmj.com
Hemorrhagic stroke
Figure 1 Definition of parameters. AR, aspect ratio; SR, size ratio; H/W, height–width ratio.
Size According to Raghavan et al,11 aneurysm size was defined as the maximum distance of the dome from the aneurysm neck plane.
from the neck plane) to the width of aneurysm, where the aneurysm width was the maximum width parallel to the neck.15
Aneurysm shape Aspect ratio (AR) The AR was calculated from the maximum perpendicular height divided by the neck width, where the neck width is twice the average length from the aneurysm neck centroid to the edge of its neck.13
Size ratio (SR) The SR was calculated from the maximum aneurysm height divided by the average vessel diameter, in accordance with Dhar et al.14 Here, the average vessel diameter could be obtained by measuring two vessel diameters (inflow vessel diameters (D) at the proximal bilateral neck and D1 at 1.5D upstream) and taking their average value. The maximum height is the maximum distance from the cross-section of the aneurysm neck to any point on the aneurysm dome. In the case of a terminal aneurysm, the average diameter of the feeding artery and the other branching vessels was used for the ‘average vessel diameter’ in our study.
Height–width ratio Height–width (H/W) ratio was defined as the ratio of height (the maximum perpendicular distance of the aneurysm dome
Aneurysm shape was categorized into regular, irregular, and with a daughter sac. Regular aneurysm was defined as spherical or ellipse. An aneurysm was defined as being irregularly-shaped when blebs, aneurysm wall protrusions, or multiple lobes were present but without a daughter aneurysm. An irregularly-shaped aneurysm with a daughter sac was categorized as aneurysm with daughter sac.
Aneurysm angles We defined four aneurysm angles—namely, flow angle, aneurysm inclination angle, parent artery angle, and vessel angle (figure 2). The flow angle (θF) was defined as the angle between the inlet vessel centerline and the maximum length,16 the aneurysm inclination angle (θA) is the angle of inclination between the aneurysm and its neck plane,14 the parent artery angle (θP) was defined as the angle between two parent arteries,14 and the vessel angle (θV) is the angle between the inlet vessel centerline and the neck plane.17 It should be noted that these angles were only defined for sidewall IAs. When the aneurysm angles were measured, the correct viewing plane was determined as follows: (1) first, the image was rotated until the aneurysm neck
Figure 2 Definition of aneurysm angles in wide-necked and narrow-necked aneurysms. 2
Zheng Y, et al. J NeuroIntervent Surg 2016;0:1–7. doi:10.1136/neurintsurg-2015-012112
Downloaded from http://jnis.bmj.com/ on January 17, 2016 - Published by group.bmj.com
Hemorrhagic stroke Table 1
Patient and aneurysm characteristics
Characteristic Women (%) Mean±SD age, years Diameter of aneurysm (mm) Mean±SD 10 mm (%) Aneurysm location OA (%) MCA (%) Acom artery (%) Pcom artery (%) Other location (%)
Aneurysm rupture (68 patients)
No aneurysm rupture (82 patients)
All patients (150 patients)
42 (61.8) 56.1±13.3
63 (76.8) 56.1±11.7
105 (70.0) 56.1±12.4
6.1±3.2 18 (26.5) 30 (44.1) 14 (20.6) 6 (8.8)
5.8±4.9 43 (52.4) 15 (18.3) 11 (13.4) 13 (15.9)
5.9±4.2 61 (40.7) 45 (30.0) 25 (16.7) 19 (12.6)
7 (10.3) 14 (20.6) 15 (22.1) 26 (38.2) 6 (8.8)
48 (58.5) 5 (6.1) 9 (11.0) 12 (14.6) 8 (9.8)
55 (36.7) 19 (12.7) 24 (16.0) 38 (25.3) 14 (9.3)
Acom artery, anterior communicating artery; MCA, middle cerebral artery; OA, ophthalmic artery; Pcom artery, posterior communicating artery.
plane was seen as a line which means that the aneurysm neck plane was perpendicular to the viewing plane (2) then, the image was rotated about an axis of rotation, which was defined perpendicularly to aneurysm neck plane through the neck centroid. The aneurysm angles were measured based on the viewing plane when the lowest value of the apparent vessel angle was chosen.14
Aneurysm location In our study the IAs were divided into five groups: posterior communicating artery, anterior communicating artery, ophthalmic artery, middle cerebral artery, and other location.
Statistical analysis The five morphological parameters described above (size, AR, SR, H/W, aneurysm shape) were calculated for each IA whereas the other four (θF, θA, θP , θV) were only calculated for sidewall IAs. Continuous variables and categorical variables were reported as mean±SD and frequency/percentage, respectively, for each group. Scatter plots for all parameters were used between ruptured and unruptured IAs and data outliers were identified for each parameter from box-and-whisker plots. The horizontal line within the box-and-whisker plots represents the median (50th percentile) while the upper and lower boundaries of the box-and-whisker plots represent the 75th and 25th percentiles, respectively. The whiskers on the upper or lower side represent those data points which lie within 1.5 box heights from the 75th or 25th percentile points. Data points located further outside the box (shown by an asterisk or circle) are regarded as outliers and those data were not further examined by the Student t test or receiver operating characteristic (ROC) analysis. The Student t test was used to examine the difference in aneurysm size, AR, SR, H/W and aneurysm angle between the two groups. The χ2 test was performed for aneurysm location and shape to assess the statistical significance. p Values and 95% CIs from the t test or χ2 test were calculated and reported. The factors found to be significant ( p
Hemorrhagic stroke
ORIGINAL RESEARCH
Assessment of intracranial aneurysm rupture based on morphology parameters and anatomical locations Yongtao Zheng,1 Feng Xu,1 Jinma Ren,2 Qiang Xu,3 Yingjun Liu,1 Yanlong Tian,1 Bing Leng1 1
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China 2 Center for Health Outcomes Research, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA 3 Department of Radiology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China Correspondence to Professor Bing Leng, Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, No 12 Wulumuqi Middle Road, Shanghai 200040, China; [email protected] YZ and FX contributed equally. Received 13 October 2015 Accepted 25 November 2015
ABSTRACT Objectives The aim of the present study was to identify image-based morphological parameters and anatomical locations associated with intracranial aneurysm (IA) rupture. Methods Nine morphological parameters and aneurysm location were evaluated in 150 patients with saccular IAs (82 unruptured, 68 ruptured) using threedimensional geometry. Aneurysm location and morphological parameters including size, aspect ratio, size ratio, height–width ratio, flow angle, aneurysm inclination angle, parent artery angle, vessel angle, and aneurysm shape were explored to identify a correlation with aneurysm rupture. These factors were analyzed using a two-tailed independent Student t test or the χ test for significance. Significant factors were further examined using logistic regression analysis. Additionally, receiver operating characteristic (ROC) analysis was performed to evaluate each parameter. Results Statistically significant differences were observed in ruptured and unruptured groups for aspect ratio, size ratio, height–width ratio, flow angle, aneurysm inclination angle, vessel angle, aneurysm shape, and aneurysm location. Logistic regression analysis further revealed that size ratio (OR 1.66; 95% CI 1.05 to 2.64), height–width ratio (OR 14.22; 95% CI 2.67 to 75.88), aneurysm inclination angle (OR 1.04; 95% CI 1.01 to 1.07), aneurysm shape (OR 4.68; 95% CI 2.44 to 8.98), and aneurysm location (OR 1.60; 95% CI 1.15 to 2.23) had the strongest independent correlation with ruptured IA. The ROC analysis showed that the size ratio and flow angle had the highest area under the curve, with values of 0.735 and 0.730, respectively. Conclusions Size ratio, height–width ratio, aneurysm inclination angle, aneurysm shape, and aneurysm location might be important for discriminating between ruptured and unruptured aneurysms. Further investigation will determine whether these morphological parameters and anatomical locations will be reliable predictors of aneurysm rupture.
INTRODUCTION
To cite: Zheng Y, Xu F, Ren J, et al. J NeuroIntervent Surg Published Online First: [please include Day Month Year] doi:10.1136/ neurintsurg-2015-012112
The annual incidence of subarachnoid hemorrhage resulting from the rupture of intracranial aneurysm (IA) is estimated at nine per 100 000 affected individuals.1 Even with the best available medical care, the majority of individuals with subarachnoid hemorrhage die or become severely disabled. Although an adequate treatment for IA is urgently needed, the postoperative morbidity and high treatment costs must be carefully considered for the
development of treatment strategies.2–4 The rupture rate of IA is significantly lower than the incidence rate. Indeed, IA affects approximately 2–5% of the entire population,5 but only 1–3% of all IAs actually rupture.6 7 Recently, Greving et al8 summarized the results of six prospective studies, reporting an average observed 1-year risk of aneurysm rupture of 1.4% and a 5-year risk of 3.4%. Thus, most IAs do not require clinical intervention. However, reliable knowledge about the risks of IA rupture in different populations will facilitate the development of planning, screening, and prevention strategies and will provide information for the prognosis of individual patients. The most ubiquitous parameter is IA size. Although aneurysms exceeding 7 or 10 mm in size are considered to be dangerous, several studies have shown that a large percentage of ruptured aneurysms are, in fact, smaller than 7 mm.9–12 The relationship between rupture risk and IA size has not been completely elucidated. Interestingly, Ujiie et al13 reported that the aspect ratio (AR) might be useful in predicting imminent aneurysmal rupture, while Dhar et al14 reported that the size ratio (SR) and aneurysm angle were meaningful morphological metrics for the assessment of rupture risk. Consistent with previous studies, we reported the importance of several morphological parameters and intracranial locations for IA rupture.
MATERIALS AND METHODS Patient population Between January 2013 and December 2014, threedimensional rotational digital subtraction angiography (DSA) images (Philips Allua Xper, The Netherlands) were obtained from patients with saccular terminal or sidewall IA treated at Huashan Hospital. One hundred and fifty consecutive patients with 82 unruptured and 68 ruptured aneurysms met these criteria. Once diagnosed as IA, DSA was performed in all patients in our hospital who were randomly enrolled in the study. Of the 150 saccular aneurysms, 125 were sidewall type and 25 were terminal type. Patients with multiple aneurysms were classified according to the size and location of the largest aneurysm observed.
Definition of parameters Nine morphology parameters and aneurysm location were defined in our study. All morphology parameters were evaluated by two neurosurgeons (FX, BL) and one radiology physician (QX) (figure 1).
Zheng Y, et al. J NeuroIntervent Surg 2016;0:1–7. doi:10.1136/neurintsurg-2015-012112
1
Downloaded from http://jnis.bmj.com/ on January 17, 2016 - Published by group.bmj.com
Hemorrhagic stroke
Figure 1 Definition of parameters. AR, aspect ratio; SR, size ratio; H/W, height–width ratio.
Size According to Raghavan et al,11 aneurysm size was defined as the maximum distance of the dome from the aneurysm neck plane.
from the neck plane) to the width of aneurysm, where the aneurysm width was the maximum width parallel to the neck.15
Aneurysm shape Aspect ratio (AR) The AR was calculated from the maximum perpendicular height divided by the neck width, where the neck width is twice the average length from the aneurysm neck centroid to the edge of its neck.13
Size ratio (SR) The SR was calculated from the maximum aneurysm height divided by the average vessel diameter, in accordance with Dhar et al.14 Here, the average vessel diameter could be obtained by measuring two vessel diameters (inflow vessel diameters (D) at the proximal bilateral neck and D1 at 1.5D upstream) and taking their average value. The maximum height is the maximum distance from the cross-section of the aneurysm neck to any point on the aneurysm dome. In the case of a terminal aneurysm, the average diameter of the feeding artery and the other branching vessels was used for the ‘average vessel diameter’ in our study.
Height–width ratio Height–width (H/W) ratio was defined as the ratio of height (the maximum perpendicular distance of the aneurysm dome
Aneurysm shape was categorized into regular, irregular, and with a daughter sac. Regular aneurysm was defined as spherical or ellipse. An aneurysm was defined as being irregularly-shaped when blebs, aneurysm wall protrusions, or multiple lobes were present but without a daughter aneurysm. An irregularly-shaped aneurysm with a daughter sac was categorized as aneurysm with daughter sac.
Aneurysm angles We defined four aneurysm angles—namely, flow angle, aneurysm inclination angle, parent artery angle, and vessel angle (figure 2). The flow angle (θF) was defined as the angle between the inlet vessel centerline and the maximum length,16 the aneurysm inclination angle (θA) is the angle of inclination between the aneurysm and its neck plane,14 the parent artery angle (θP) was defined as the angle between two parent arteries,14 and the vessel angle (θV) is the angle between the inlet vessel centerline and the neck plane.17 It should be noted that these angles were only defined for sidewall IAs. When the aneurysm angles were measured, the correct viewing plane was determined as follows: (1) first, the image was rotated until the aneurysm neck
Figure 2 Definition of aneurysm angles in wide-necked and narrow-necked aneurysms. 2
Zheng Y, et al. J NeuroIntervent Surg 2016;0:1–7. doi:10.1136/neurintsurg-2015-012112
Downloaded from http://jnis.bmj.com/ on January 17, 2016 - Published by group.bmj.com
Hemorrhagic stroke Table 1
Patient and aneurysm characteristics
Characteristic Women (%) Mean±SD age, years Diameter of aneurysm (mm) Mean±SD 10 mm (%) Aneurysm location OA (%) MCA (%) Acom artery (%) Pcom artery (%) Other location (%)
Aneurysm rupture (68 patients)
No aneurysm rupture (82 patients)
All patients (150 patients)
42 (61.8) 56.1±13.3
63 (76.8) 56.1±11.7
105 (70.0) 56.1±12.4
6.1±3.2 18 (26.5) 30 (44.1) 14 (20.6) 6 (8.8)
5.8±4.9 43 (52.4) 15 (18.3) 11 (13.4) 13 (15.9)
5.9±4.2 61 (40.7) 45 (30.0) 25 (16.7) 19 (12.6)
7 (10.3) 14 (20.6) 15 (22.1) 26 (38.2) 6 (8.8)
48 (58.5) 5 (6.1) 9 (11.0) 12 (14.6) 8 (9.8)
55 (36.7) 19 (12.7) 24 (16.0) 38 (25.3) 14 (9.3)
Acom artery, anterior communicating artery; MCA, middle cerebral artery; OA, ophthalmic artery; Pcom artery, posterior communicating artery.
plane was seen as a line which means that the aneurysm neck plane was perpendicular to the viewing plane (2) then, the image was rotated about an axis of rotation, which was defined perpendicularly to aneurysm neck plane through the neck centroid. The aneurysm angles were measured based on the viewing plane when the lowest value of the apparent vessel angle was chosen.14
Aneurysm location In our study the IAs were divided into five groups: posterior communicating artery, anterior communicating artery, ophthalmic artery, middle cerebral artery, and other location.
Statistical analysis The five morphological parameters described above (size, AR, SR, H/W, aneurysm shape) were calculated for each IA whereas the other four (θF, θA, θP , θV) were only calculated for sidewall IAs. Continuous variables and categorical variables were reported as mean±SD and frequency/percentage, respectively, for each group. Scatter plots for all parameters were used between ruptured and unruptured IAs and data outliers were identified for each parameter from box-and-whisker plots. The horizontal line within the box-and-whisker plots represents the median (50th percentile) while the upper and lower boundaries of the box-and-whisker plots represent the 75th and 25th percentiles, respectively. The whiskers on the upper or lower side represent those data points which lie within 1.5 box heights from the 75th or 25th percentile points. Data points located further outside the box (shown by an asterisk or circle) are regarded as outliers and those data were not further examined by the Student t test or receiver operating characteristic (ROC) analysis. The Student t test was used to examine the difference in aneurysm size, AR, SR, H/W and aneurysm angle between the two groups. The χ2 test was performed for aneurysm location and shape to assess the statistical significance. p Values and 95% CIs from the t test or χ2 test were calculated and reported. The factors found to be significant ( p
