ORIGINAL ARTICLE
320-Row Multidetector Computed Tomographic Angiogram in the Evaluation of Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Pilot Study Julien Hébert,* Federico Roncarolo, MD, PhD,† Donatella Tampieri, MD, FRCPC,‡ and Maria delPilar Cortes, MD‡ Objective: To objectively assess the accuracy of 320-row multidetector computed tomographic (CT) angiography to diagnose cerebral vasospasm after a subarachnoid hemorrhage using a new quantitative method. Methods: Fifty-four arterial segments were measured in 8 patients who had subarachnoid hemorrhage and underwent digital subtraction angiography within 24 hours after CT angiography for clinical suspicion of cerebral vasospasm. Results: A correlation between arterial diameters measurements made on CTangiography and digital subtraction angiography was observed. The degree of vasospasm tended to be overestimated in the anterior circulation, with arterial diameters that were between 0.05 and 0.72 mm smaller than those on digital subtraction angiography. Conclusions: A quantitative approach can be used to objectively evaluate the ability of multidetector CT angiography to assess arterial diameter in patients with clinical symptoms of postsubarachnoid hemorrhage cerebral vasospasm. This pilot study also suggests that CT angiography may overestimate the degree of cerebral vasospasm in the anterior circulation. Key Words: intracranial vasospasm, tomography, x-ray computed, digital subtraction angiography (J Comput Assist Tomogr 2015;39: 541–546)
A
neurysmal subarachnoid hemorrhage (ASAH) is a devastating condition that affects annually 3 to 25 per 100,000 persons worldwide.1 Thirty-day mortality reaches 50%, and only half of the survivors are able to live independently.2,3 Aneurysmal subarachnoid hemorrhage typically presents with a sudden onset of severe headache, nausea, vomiting, neck pain, photophobia, and loss of consciousness.4 Patients who survive early complications, such as hydrocephalus and rebleeding, will then be faced with the much-dreaded risk of cerebral vasospasm, with a typical onset of 3 to 5 days posthemorrhage and maximal narrowing at days 5 to 14.5,6 Arterial narrowing can be seen in approximately 40% of patients with ASAH, and 20% to 30% of patients with ASAH develop the neurologic deficits of vasospasm.5,7–9 Typical symptoms of vasospasm include a new focal neurologic deficit unexplained by rebleeding or hydrocephalus and altered level of consciousness.6 Cerebral vasospasm is thought to lead to neurologic deficits through delayed cerebral ischemia,5,10 although the role of reduced vessel diameter in this process remains unclear.11 From the *Faculty of Medicine, McGill University, Montreal, Quebec, Canada; †Institute de recherche en santé publique de l'université de Montréal, Montreal, Quebec, Canada; and ‡Montreal Neurological Hospital and Institute, Montreal, Quebec, Canada. Received for publication November 22, 2014; accepted February 23, 2015. Reprints: Maria delPilar Cortes, MD, Radiology Department, Montreal Neurological Hospital and Institute, 3801 University St, Fifth Floor Radiology, Rm 540A, Montreal, Quebec, Canada H3A2B4 (e‐mail: [email protected]). Julien Hébert received funding through the McGill Faculty of Medicine Research Bursary program. The other authors declare no conflict of interest. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Despite some controversy concerning its effectiveness,12,13 the first-line therapeutic approach to vasospasm is triple-H therapy (ie, hypervolemia, hypertension, and hemodilution). The putative effect of this therapy is to increase cerebral blood flow and thus decrease the risks of cerebral ischemia.14 Despite attempts to find new therapies to prevent and treat vasospasm,15 it remains the leading cause of death and mortality in patients surviving the initial ASAH treatment.3 The current gold standard in the diagnosis of cerebral vasospasm is cerebral digital subtraction angiography (DSA). The major advantages of this technique are that it is extremely accurate and allows for immediate endovascular treatment. Endovascular treatment options include balloon angioplasty, alone or in combination with an injection of vasodilator drug directly into the cerebral circulation. Digital subtraction angiography is, however, an invasive and costly procedure that can lead to severe complications, including stroke.16 Noninvasive measures have been increasingly used to detect vasospasm in patients who had an ASAH. One of these techniques, transcranial Doppler ultrasonography, is commonly used in many centers. Its low specificity and high operator dependence, however, make it a suboptimal detection tool for vasospasm.17 Computed tomographic (CT) angiography (CTA) is another noninvasive imaging technique, which promises to be a more accurate tool in the evaluation of vasospasm. Within the last decade, the use of multidetector CTA, which allows for faster image acquisition and decreased radiation exposure, has become increasingly popular. The objective of this pilot study is to test a new quantitative approach to evaluate the ability of 320-row multidetector CTA to assess arterial diameter, using DSA as the gold standard, in patients with clinical symptoms of cerebral vasospasm after a subarachnoid hemorrhage (SAH). This will be achieved by comparing the arterial diameters obtained on CTA with those obtained on DSA using arterial diameter as a continuous variable. We hypothesize that the 320-row multidetector CTA is an accurate, noninvasive tool in assessing cerebral vasospasm in patients with an SAH, but that, based on the clinical experience so far, it may have a tendency to overestimate the degree of vasospasm.
MATERIALS AND METHODS Population Data for this study were retrospectively collected using the database of all patients who underwent a 320-row multidetector CTA for the circle of Willis at our institution between February 2010 and February 2013. The inclusion criteria were as follows: diagnosis of SAH after aneurysmal rupture, angiographic vasospasm on CTA and/or DSA, and DSA performed within 24 hours after CTA. The studies were acquired either upon admission of the patient with ASAH (n = 6 patients) or an average of 7 days after admission for ASAH given clinical suspicion of vasospasm (n = 2 patients). In our institution, the current standard of care is to first evaluate ruptured aneurysms for endovascular treatment
J Comput Assist Tomogr • Volume 39, Number 4, July/August 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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(coiling) using CTA and to routinely administer nimodipine to patients with a confirmed ASAH. Because nimodipine reduces poor outcomes without preventing or treating angiographic vasospasm itself, its administration should not interfere with arterial diameters.18,19 If endovascular treatment is either judged too risky or fails, surgical clipping of the ruptured aneurysm is performed by a neurosurgeon. All patients with ASAH were managed in the intensive care unit with a special attention to preserve euvolemia and maintain cerebral perfusion. Patients who developed signs of clinical vasospasm were then screened for cerebral vasospasm using CTA. If the latter suggested vasospasm, patients were then treated with milrinone and triple-H therapy. If the clinical response was unsatisfactory, patients underwent DSA for further assessment and endovascular treatment.
DSA (Advantx [GE Healthcare, Waukesha, WI] for 3 participants; Infinix-i [Toshiba Medical Systems] for 5 participants) was performed using a transfemoral approach. Using a #4 French Osborn catheter, selective catheterization of the vessels was performed. Anteroposterior, lateral, and, when necessary, oblique views or 3-dimensional (3-D) angiography of bilateral vertebral and internal carotid artery (ICA) injections were obtained. The contrast media (Iodixanol, Visipaque; GE Healthcare Ireland, Cork, Ireland) was injected either manually or through a power injector (BRACCO E-Z EM EmpowerCTA Dual Injector; Siemens Medical Solutions). For the ICA, the rate of injection was 4 mL/s for a total of 6 mL, whereas for the vertebral arteries, the injection rate was 3 mL/s for a total volume of 5 mL.
CT Angiogram
This study used arterial diameter of the circle of Willis as a means to quantitatively assess the accuracy of the 320-row multidetector CTA to detect cerebral vasospasm. The arterial diameters on CTA and DSA were independently measured twice by 2 experienced neurointerventionists. Each reader was required to take the measurement for both CTA and DSA using the calibrated “linear measurement tool” from the Intelerad's InteleViewer system (version 4-2-1-P355; Intelerad, Westminster, CO). Calibration was required for 5 of the 8 cerebral angiograms. The cavernous internal carotid arteries, assumed to be 5.9 mm in diameter, and the basilar artery, assumed to be 4.1 mm in diameter, were used as internal standards.20,21 The Intelerad's “Arrow Annotation Tool” was used to ensure that measurements were taken at the same location by both readers (see Figs. 1A, B) For both CTA and DSA, 9 arterial segments were measured: bilateral proximal anterior cerebral artery (A1), bilateral proximal middle cerebral artery (M1), bilateral proximal posterior cerebral artery (P1), bilateral supraclinoid segment of the ICA, and distal basilar artery. Arterial diameters on CTA were measured on axial, coronal, and sagittal source images for each vessel, and an average of the 3 values was obtained for each vessel. No reconstructed images, such as mean intensity projection or 3-D vessel reconstruction, were used to
All CTA images were acquired using a 320-row multidetector CT scanner (Aquilion One; Toshiba Medical Systems, Tokyo, Japan). Scanning was from skull base to vertex. Intravenous iodinated contrast material (iopamidol, Isovue 370; Regional Health Limited, Auckland, New Zealand) was administered peripherally with an automated injector (BRACCO E-Z EM EmpowerCTA Dual Injector; Siemens Medical Solutions, Malvern, PA). A test bolus, consisting of 20 mL of contrast material injected at 4 mL/s followed by 20 mL of saline at 4 mL/s, was administered before image acquisition. Then 60 mL of contrast material was injected at 4 mL/s, followed by 20 to 40 mL of saline for the acquisition of images. Adequate timing of the CTA acquisition was achieved using a bolus-tracking technique. Acquisition parameters were as follows: 150 mA; 80 kV (n = 4) or 300 mA; 120 kV (n = 4); matrix, 512 512; field of view, 220 220 mm; and section thickness, 1.5 mm on average (range, 0.5–3.0 mm).
Cerebral Digital Subtraction Angiogram With the patient under localized or general anesthesia, the right groin was prepared using standard techniques. Biplane
Image Analysis
FIGURE 1. A and B, Measurement of the diameter of the basilar artery segment (green arrows) on CTA (A) and DSA (B) in sagittal view. The participant had post-SAH cerebral vasospasm. A large aneurysm can be seen at the tip of the basilar artery. The “arrow” and “ruler” tools of our PACS allow for consistent and objective measurements of this arterial diameter between the 2 readers. Figure 1 can be viewed online in color at www.jcat.org.
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© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Comput Assist Tomogr • Volume 39, Number 4, July/August 2015
320-Row Multidetector CTA for Cerebral Vasospasm
RESULTS
TABLE 1. Patients Characteristics Sex, no. (%) Men Women Age of the patients (range), y History of SAH, no. (%) IVDU, no. (%) Smokers, no. (%) Hypertension, no. (%) Diabetic, no. (%) SAH grade on H&H scale, no. (%) Grade I Grade II Grade III Grade IV Grade V Delay between - Diagnosis of SAH to diagnosis of vasospasm on CTA (range), d - CTA to DSA (range), min Treatment, no. (%) Nimodipine Milrinone Coiling Clipping Location of aneurysm, no (%) Anterior circulation Posterior circulation
Patients 1 (12.5) 7 (87.5) 59.4 (46–88) 1 (12.5) 0 (0) 7 (87.5) 2 (25) 0 (0) 2 (25) 3 (37.5) 3 (37.5) 0 (0) 0 (0) 7.625 (2–13)
Eight patients were found to fulfill the inclusion criteria after looking at the files of 987 patients who underwent CTA of the circle of Willis between February 2010 and February 2013 (see Table 1).
Interobserver Variability There was significant interobserver agreement for measurement of arterial diameters on both CTA and DSA (see Table 2). For CTA, the intraclass correlation coefficients ranged between 0.809 and 0.992, with P values between less than 0.0005 and 0.017. Regarding DSA, statistical agreement could not be reached between the 2 readers for the measurement of the right posterior cerebral artery diameter only, with an intraclass coefficient of 0.740 and a P value of 0.102. Measurement for all other arterial segments on DSA, however, showed excellent agreement between the 2 readers, with intraclass correlation coefficients ranging between 0.795 and 0.988 and P values ranging between less than 0.0005 and 0.008.
562 (36–1408) 7 (87.5) 5 (62.5) 5 (62.5) 1 (12.5) 7 (87.5) 1 (12.5)
IVDU indicates intravenous drug user; H&H, Hunt and Hess.
avoid bias from the interpretation necessary to make these reconstructions. To ensure that the same section of artery was measured on all 3 planes of the CTA, the Intelerad's “3-D cursor” tool was used for appropriate cross matching between planes. Arterial diameters on DSA were measured in an anteroposterior view. In addition, the supraclinoid segment of the bilateral internal carotid arteries was also measured in a lateral view on DSA. The source images and not the 3-D vessel reconstruction images were also used for the DSA. Magnification of the images was kept constant between readers for both CTA (5.00 25%) and DSA (2.00 25%). Windowing was also kept constant between the 2 readers.
Arterial Diameters Eighteen vessels could not be measured due to artifact (n = 2), hypoplastic vessels (n = 4), and lack of angiographic imaging (n = 12). Fifty-four arterial segments were measured on both CTA and DSA. A total of 324 arterial diameter measurements were taken on CTA by both radiologists in 3 different views, whereas 134 arterial diameter measurements were taken on angiography. Paired-sample t test was performed to compare the arterial diameters for each vessel as measured on CTA with those measured on angiography. Except for the left middle cerebral artery, the arterial diameters for the anterior circulation were always larger on angiography than on CTA, with differences between the diameters acquired by the 2 imaging techniques ranging between 0.05 and 0.72 mm. Regarding the posterior circulation, the trend was reversed, with arterial diameters being smaller on angiography than on CTA and with the CTA being between 0.04 and 0.31 mm larger than the angiography. These differences in arterial diameters for both the anterior and posterior circulation were,
TABLE 2. Intraclass Correlation Coefficients for Interobserver Measurements of Arterial Diameters on CTA and DSA CTA
Statistical Analysis The statistical analysis was performed using IBM SPSS. Intraclass correlation coefficient was calculated for each of the 9 arteries to assess the reliability of the arterial diameter measurements performed by the 2 neuroradiologists. For the comparison of arterial segments as measured with CTA with those measured on DSA, an arterial diameter value was calculated for each of the 9 vessels assessed for each study participant, for both CTA and DSA. This unique arterial diameter value was obtained by averaging the measurements taken by both radiologists in all different views. The arterial diameters were then analyzed for differences between CTA and DSA using paired sample t test. Pearson correlation coefficients were also used to determine the presence or absence of correlation between arterial diameters taken on the CTA with those taken on DSA.
Artery Left ICA Right ICA Left ACA Right ACA Left MCA Right MCA Left PCA Right PCA Basilar artery
Intraclass Coefficient 0.992 0.974 0.978 0.809 0.972 0.905 0.961 0.959 0.956
DSA P
Intraclass Coefficient
P
0.000 0.001 0.001 0.007 0.000 0.008 0.017 0.004 0.004
0.966 0.984 0.980 0.943 0.988 0.932 0.795 0.740 0.973
0.000 0.000 0.001 0.001 0.000 0.000 0.008 0.102 0.001
ACA indicates anterior carotid artery; MCA, middle cerebral artery; PCA, posterior cerebral artery.
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however, not statistically significant (0.100 < P < 0.943). There were no statistically significant correlations between the arterial diameters measured with CTA and those measured with angiography (Figs. 2–4; Table 3).
DISCUSSION This pilot study is, to our knowledge, the first study that uses a 320-row multidetector CTA in the evaluation of cerebral vasospasm after an ASAH. This is also the first study to adopt a quantitative approach to assess the use of CTA in the evaluation of this condition. All previous studies on this topic have adopted a categorical approach that classifies the degree of severity of cerebral vasospasm into different categories (eg, mild, moderate, and severe) based on radiologic imaging findings.22–28 The advantage of the categorical approach is that, unlike this study, sensitivity, specificity, and positive and negative predictive values can be calculated by comparing the classification obtained from CTA with that obtained from DSA. However, in addition to being less objective, the challenge with these studies is that they almost all use different classification systems, thus making comparison between them challenging. The only exception was Otawara et al29 and Shankar et al,22 who both used the scale of Schneck and Kricheff30 (none, 0% arterial narrowing; mild, 60% arterial narrowing). Chaudhary et al23 used the method from the warfarinAspirin Symptomatic Intracranial Disease Study,24 whereas Yoon et al,25 Anderson et al,26 Binaghi et al,27 and Wintermark et al28 used their own arbitrarily defined scale, with different cutoff values of arterial narrowing to define the different degrees of vasospasm.
FIGURE 2. Anteroposterior view of DSA of the right ICA showing diffuse vasospasm in the supraclinoid ICA (arrowhead), anterior cerebral artery (thick arrow), and the middle cerebral artery (thin arrow). A small saccular aneurysm is seen on top of the unpaired pericallosal artery (asterisk). Figure 2 can be viewed online in color at www.jcat.org.
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FIGURE 3. Axial view of CTA source image of the same patient as in Figure 2. Note the narrowing of the ACA vessels (thick arrows). Figure 3 can be viewed online in color at www.jcat.org.
Allowing for the limitations of CTA, the trend observed within the literature using this discreet approach is that CTA is acknowledged as a valid method to evaluate vasospasm in patients who had an ASAH, with a sensitivity ranging between 63% and 97.5%, a specificity between 90% and 100%, a positive predictive value between 43% and 98.3%, a negative predictive value between 94.1% and 99.5%, and an accuracy between
FIGURE 4. Computer 3-D reconstruction of CTA showing diffuse vasospasm (thick arrows). Figure 4 can be viewed online in color at www.jcat.org. © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Comput Assist Tomogr • Volume 39, Number 4, July/August 2015
320-Row Multidetector CTA for Cerebral Vasospasm
TABLE 3. Arterial Diameters Measured on CTA and DSA Arterial Diameter, mean ± SD, mm Artery Left ICA Right ICA Left ACA Right ACA Left MCA Right MCA Left PCA Right PCA Basilar artery
No. Arteries Included
CTA Measurement
DSA Measurement
7 6 5 8 7 7 4 5 5
2.5807 ± 0.58953 2.7383 ± 0.52190 1.5890 ± 0.48952 1.4019 ± 0.22581 2.0743 ± 0.48584 1.9221 ± 0.26932 1.7650 ± 0.28595 1.8410 ± 0.46790 2.7100 ± 0.51573
3.3000 ± 1.29365 3.0458 ± 0.94953 1.6400 ± 1.29923 1.6250 ± 0.86479 2.0500 ± 1.02713 2.1286 ± 1.09729 1.7250 ± 0.57373 1.5800 ± 0.46449 2.4000 ± 0.62948
ACA indicates anterior carotid artery; MCA, middle cerebral artery; PCA, posterior cerebral artery.
87% and 98%22,23,25–28 (see Table 4). Otawara et al29 did not calculate the sensitivity, specificity, and negative and positive predictive values of CTA in detecting cerebral vasospasm, but have found CTA to be 91.6% accurate. Some of these studies suggest that the sensitivity, specificity, and accuracy of CTA are usually lower in distal vessels than in proximal vessels.22,23,25,26 However, this trend could not be verified in our study because only proximal arterial diameters were measured. Other studies have adopted a quantitative approach similar to the one we adopted to evaluate the accuracy of multidetector CTA, but none have investigated patients in whom cerebral vasospasm was suspected after an ASAH. For instance, Ferguson et al,31 using 4-, 16-, 40-, and 64-row multidetector CTA, compared arterial diameters measurements obtained on CTA with those obtained on DSA in patients with aneurysms. Clinical suspicion of vasospasm was not part of the inclusion criteria. When analyzed as a continuous variable, there was a significant correlation between DSA arterial diameters and corresponding axial CTA images for all the arteries measured (R2 ranging between 0.45 and 0.76, P < 0.0001). It was nevertheless observed that CTA tended to overestimate the arterial narrowing of larger arteries and underestimate the measurement of smaller arteries. This goes in line with the trend observed in this study: in the anterior circulation, arterial diameters seem to be smaller when measured on CTA than on DSA. Based on our initial experience, the degree of inconsistency seems minimal. However, this remains to be proven with a larger sample size. That the same trend could
not be observed in the posterior circulation vessels could be simply explained by greater ease at measuring posterior cerebral circulation on CTA. Interestingly, when Fergusson et al31 divided arterial diameters into different categories (
320-Row Multidetector Computed Tomographic Angiogram in the Evaluation of Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Pilot Study Julien Hébert,* Federico Roncarolo, MD, PhD,† Donatella Tampieri, MD, FRCPC,‡ and Maria delPilar Cortes, MD‡ Objective: To objectively assess the accuracy of 320-row multidetector computed tomographic (CT) angiography to diagnose cerebral vasospasm after a subarachnoid hemorrhage using a new quantitative method. Methods: Fifty-four arterial segments were measured in 8 patients who had subarachnoid hemorrhage and underwent digital subtraction angiography within 24 hours after CT angiography for clinical suspicion of cerebral vasospasm. Results: A correlation between arterial diameters measurements made on CTangiography and digital subtraction angiography was observed. The degree of vasospasm tended to be overestimated in the anterior circulation, with arterial diameters that were between 0.05 and 0.72 mm smaller than those on digital subtraction angiography. Conclusions: A quantitative approach can be used to objectively evaluate the ability of multidetector CT angiography to assess arterial diameter in patients with clinical symptoms of postsubarachnoid hemorrhage cerebral vasospasm. This pilot study also suggests that CT angiography may overestimate the degree of cerebral vasospasm in the anterior circulation. Key Words: intracranial vasospasm, tomography, x-ray computed, digital subtraction angiography (J Comput Assist Tomogr 2015;39: 541–546)
A
neurysmal subarachnoid hemorrhage (ASAH) is a devastating condition that affects annually 3 to 25 per 100,000 persons worldwide.1 Thirty-day mortality reaches 50%, and only half of the survivors are able to live independently.2,3 Aneurysmal subarachnoid hemorrhage typically presents with a sudden onset of severe headache, nausea, vomiting, neck pain, photophobia, and loss of consciousness.4 Patients who survive early complications, such as hydrocephalus and rebleeding, will then be faced with the much-dreaded risk of cerebral vasospasm, with a typical onset of 3 to 5 days posthemorrhage and maximal narrowing at days 5 to 14.5,6 Arterial narrowing can be seen in approximately 40% of patients with ASAH, and 20% to 30% of patients with ASAH develop the neurologic deficits of vasospasm.5,7–9 Typical symptoms of vasospasm include a new focal neurologic deficit unexplained by rebleeding or hydrocephalus and altered level of consciousness.6 Cerebral vasospasm is thought to lead to neurologic deficits through delayed cerebral ischemia,5,10 although the role of reduced vessel diameter in this process remains unclear.11 From the *Faculty of Medicine, McGill University, Montreal, Quebec, Canada; †Institute de recherche en santé publique de l'université de Montréal, Montreal, Quebec, Canada; and ‡Montreal Neurological Hospital and Institute, Montreal, Quebec, Canada. Received for publication November 22, 2014; accepted February 23, 2015. Reprints: Maria delPilar Cortes, MD, Radiology Department, Montreal Neurological Hospital and Institute, 3801 University St, Fifth Floor Radiology, Rm 540A, Montreal, Quebec, Canada H3A2B4 (e‐mail: [email protected]). Julien Hébert received funding through the McGill Faculty of Medicine Research Bursary program. The other authors declare no conflict of interest. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Despite some controversy concerning its effectiveness,12,13 the first-line therapeutic approach to vasospasm is triple-H therapy (ie, hypervolemia, hypertension, and hemodilution). The putative effect of this therapy is to increase cerebral blood flow and thus decrease the risks of cerebral ischemia.14 Despite attempts to find new therapies to prevent and treat vasospasm,15 it remains the leading cause of death and mortality in patients surviving the initial ASAH treatment.3 The current gold standard in the diagnosis of cerebral vasospasm is cerebral digital subtraction angiography (DSA). The major advantages of this technique are that it is extremely accurate and allows for immediate endovascular treatment. Endovascular treatment options include balloon angioplasty, alone or in combination with an injection of vasodilator drug directly into the cerebral circulation. Digital subtraction angiography is, however, an invasive and costly procedure that can lead to severe complications, including stroke.16 Noninvasive measures have been increasingly used to detect vasospasm in patients who had an ASAH. One of these techniques, transcranial Doppler ultrasonography, is commonly used in many centers. Its low specificity and high operator dependence, however, make it a suboptimal detection tool for vasospasm.17 Computed tomographic (CT) angiography (CTA) is another noninvasive imaging technique, which promises to be a more accurate tool in the evaluation of vasospasm. Within the last decade, the use of multidetector CTA, which allows for faster image acquisition and decreased radiation exposure, has become increasingly popular. The objective of this pilot study is to test a new quantitative approach to evaluate the ability of 320-row multidetector CTA to assess arterial diameter, using DSA as the gold standard, in patients with clinical symptoms of cerebral vasospasm after a subarachnoid hemorrhage (SAH). This will be achieved by comparing the arterial diameters obtained on CTA with those obtained on DSA using arterial diameter as a continuous variable. We hypothesize that the 320-row multidetector CTA is an accurate, noninvasive tool in assessing cerebral vasospasm in patients with an SAH, but that, based on the clinical experience so far, it may have a tendency to overestimate the degree of vasospasm.
MATERIALS AND METHODS Population Data for this study were retrospectively collected using the database of all patients who underwent a 320-row multidetector CTA for the circle of Willis at our institution between February 2010 and February 2013. The inclusion criteria were as follows: diagnosis of SAH after aneurysmal rupture, angiographic vasospasm on CTA and/or DSA, and DSA performed within 24 hours after CTA. The studies were acquired either upon admission of the patient with ASAH (n = 6 patients) or an average of 7 days after admission for ASAH given clinical suspicion of vasospasm (n = 2 patients). In our institution, the current standard of care is to first evaluate ruptured aneurysms for endovascular treatment
J Comput Assist Tomogr • Volume 39, Number 4, July/August 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.jcat.org
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J Comput Assist Tomogr • Volume 39, Number 4, July/August 2015
Hébert et al
(coiling) using CTA and to routinely administer nimodipine to patients with a confirmed ASAH. Because nimodipine reduces poor outcomes without preventing or treating angiographic vasospasm itself, its administration should not interfere with arterial diameters.18,19 If endovascular treatment is either judged too risky or fails, surgical clipping of the ruptured aneurysm is performed by a neurosurgeon. All patients with ASAH were managed in the intensive care unit with a special attention to preserve euvolemia and maintain cerebral perfusion. Patients who developed signs of clinical vasospasm were then screened for cerebral vasospasm using CTA. If the latter suggested vasospasm, patients were then treated with milrinone and triple-H therapy. If the clinical response was unsatisfactory, patients underwent DSA for further assessment and endovascular treatment.
DSA (Advantx [GE Healthcare, Waukesha, WI] for 3 participants; Infinix-i [Toshiba Medical Systems] for 5 participants) was performed using a transfemoral approach. Using a #4 French Osborn catheter, selective catheterization of the vessels was performed. Anteroposterior, lateral, and, when necessary, oblique views or 3-dimensional (3-D) angiography of bilateral vertebral and internal carotid artery (ICA) injections were obtained. The contrast media (Iodixanol, Visipaque; GE Healthcare Ireland, Cork, Ireland) was injected either manually or through a power injector (BRACCO E-Z EM EmpowerCTA Dual Injector; Siemens Medical Solutions). For the ICA, the rate of injection was 4 mL/s for a total of 6 mL, whereas for the vertebral arteries, the injection rate was 3 mL/s for a total volume of 5 mL.
CT Angiogram
This study used arterial diameter of the circle of Willis as a means to quantitatively assess the accuracy of the 320-row multidetector CTA to detect cerebral vasospasm. The arterial diameters on CTA and DSA were independently measured twice by 2 experienced neurointerventionists. Each reader was required to take the measurement for both CTA and DSA using the calibrated “linear measurement tool” from the Intelerad's InteleViewer system (version 4-2-1-P355; Intelerad, Westminster, CO). Calibration was required for 5 of the 8 cerebral angiograms. The cavernous internal carotid arteries, assumed to be 5.9 mm in diameter, and the basilar artery, assumed to be 4.1 mm in diameter, were used as internal standards.20,21 The Intelerad's “Arrow Annotation Tool” was used to ensure that measurements were taken at the same location by both readers (see Figs. 1A, B) For both CTA and DSA, 9 arterial segments were measured: bilateral proximal anterior cerebral artery (A1), bilateral proximal middle cerebral artery (M1), bilateral proximal posterior cerebral artery (P1), bilateral supraclinoid segment of the ICA, and distal basilar artery. Arterial diameters on CTA were measured on axial, coronal, and sagittal source images for each vessel, and an average of the 3 values was obtained for each vessel. No reconstructed images, such as mean intensity projection or 3-D vessel reconstruction, were used to
All CTA images were acquired using a 320-row multidetector CT scanner (Aquilion One; Toshiba Medical Systems, Tokyo, Japan). Scanning was from skull base to vertex. Intravenous iodinated contrast material (iopamidol, Isovue 370; Regional Health Limited, Auckland, New Zealand) was administered peripherally with an automated injector (BRACCO E-Z EM EmpowerCTA Dual Injector; Siemens Medical Solutions, Malvern, PA). A test bolus, consisting of 20 mL of contrast material injected at 4 mL/s followed by 20 mL of saline at 4 mL/s, was administered before image acquisition. Then 60 mL of contrast material was injected at 4 mL/s, followed by 20 to 40 mL of saline for the acquisition of images. Adequate timing of the CTA acquisition was achieved using a bolus-tracking technique. Acquisition parameters were as follows: 150 mA; 80 kV (n = 4) or 300 mA; 120 kV (n = 4); matrix, 512 512; field of view, 220 220 mm; and section thickness, 1.5 mm on average (range, 0.5–3.0 mm).
Cerebral Digital Subtraction Angiogram With the patient under localized or general anesthesia, the right groin was prepared using standard techniques. Biplane
Image Analysis
FIGURE 1. A and B, Measurement of the diameter of the basilar artery segment (green arrows) on CTA (A) and DSA (B) in sagittal view. The participant had post-SAH cerebral vasospasm. A large aneurysm can be seen at the tip of the basilar artery. The “arrow” and “ruler” tools of our PACS allow for consistent and objective measurements of this arterial diameter between the 2 readers. Figure 1 can be viewed online in color at www.jcat.org.
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© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Comput Assist Tomogr • Volume 39, Number 4, July/August 2015
320-Row Multidetector CTA for Cerebral Vasospasm
RESULTS
TABLE 1. Patients Characteristics Sex, no. (%) Men Women Age of the patients (range), y History of SAH, no. (%) IVDU, no. (%) Smokers, no. (%) Hypertension, no. (%) Diabetic, no. (%) SAH grade on H&H scale, no. (%) Grade I Grade II Grade III Grade IV Grade V Delay between - Diagnosis of SAH to diagnosis of vasospasm on CTA (range), d - CTA to DSA (range), min Treatment, no. (%) Nimodipine Milrinone Coiling Clipping Location of aneurysm, no (%) Anterior circulation Posterior circulation
Patients 1 (12.5) 7 (87.5) 59.4 (46–88) 1 (12.5) 0 (0) 7 (87.5) 2 (25) 0 (0) 2 (25) 3 (37.5) 3 (37.5) 0 (0) 0 (0) 7.625 (2–13)
Eight patients were found to fulfill the inclusion criteria after looking at the files of 987 patients who underwent CTA of the circle of Willis between February 2010 and February 2013 (see Table 1).
Interobserver Variability There was significant interobserver agreement for measurement of arterial diameters on both CTA and DSA (see Table 2). For CTA, the intraclass correlation coefficients ranged between 0.809 and 0.992, with P values between less than 0.0005 and 0.017. Regarding DSA, statistical agreement could not be reached between the 2 readers for the measurement of the right posterior cerebral artery diameter only, with an intraclass coefficient of 0.740 and a P value of 0.102. Measurement for all other arterial segments on DSA, however, showed excellent agreement between the 2 readers, with intraclass correlation coefficients ranging between 0.795 and 0.988 and P values ranging between less than 0.0005 and 0.008.
562 (36–1408) 7 (87.5) 5 (62.5) 5 (62.5) 1 (12.5) 7 (87.5) 1 (12.5)
IVDU indicates intravenous drug user; H&H, Hunt and Hess.
avoid bias from the interpretation necessary to make these reconstructions. To ensure that the same section of artery was measured on all 3 planes of the CTA, the Intelerad's “3-D cursor” tool was used for appropriate cross matching between planes. Arterial diameters on DSA were measured in an anteroposterior view. In addition, the supraclinoid segment of the bilateral internal carotid arteries was also measured in a lateral view on DSA. The source images and not the 3-D vessel reconstruction images were also used for the DSA. Magnification of the images was kept constant between readers for both CTA (5.00 25%) and DSA (2.00 25%). Windowing was also kept constant between the 2 readers.
Arterial Diameters Eighteen vessels could not be measured due to artifact (n = 2), hypoplastic vessels (n = 4), and lack of angiographic imaging (n = 12). Fifty-four arterial segments were measured on both CTA and DSA. A total of 324 arterial diameter measurements were taken on CTA by both radiologists in 3 different views, whereas 134 arterial diameter measurements were taken on angiography. Paired-sample t test was performed to compare the arterial diameters for each vessel as measured on CTA with those measured on angiography. Except for the left middle cerebral artery, the arterial diameters for the anterior circulation were always larger on angiography than on CTA, with differences between the diameters acquired by the 2 imaging techniques ranging between 0.05 and 0.72 mm. Regarding the posterior circulation, the trend was reversed, with arterial diameters being smaller on angiography than on CTA and with the CTA being between 0.04 and 0.31 mm larger than the angiography. These differences in arterial diameters for both the anterior and posterior circulation were,
TABLE 2. Intraclass Correlation Coefficients for Interobserver Measurements of Arterial Diameters on CTA and DSA CTA
Statistical Analysis The statistical analysis was performed using IBM SPSS. Intraclass correlation coefficient was calculated for each of the 9 arteries to assess the reliability of the arterial diameter measurements performed by the 2 neuroradiologists. For the comparison of arterial segments as measured with CTA with those measured on DSA, an arterial diameter value was calculated for each of the 9 vessels assessed for each study participant, for both CTA and DSA. This unique arterial diameter value was obtained by averaging the measurements taken by both radiologists in all different views. The arterial diameters were then analyzed for differences between CTA and DSA using paired sample t test. Pearson correlation coefficients were also used to determine the presence or absence of correlation between arterial diameters taken on the CTA with those taken on DSA.
Artery Left ICA Right ICA Left ACA Right ACA Left MCA Right MCA Left PCA Right PCA Basilar artery
Intraclass Coefficient 0.992 0.974 0.978 0.809 0.972 0.905 0.961 0.959 0.956
DSA P
Intraclass Coefficient
P
0.000 0.001 0.001 0.007 0.000 0.008 0.017 0.004 0.004
0.966 0.984 0.980 0.943 0.988 0.932 0.795 0.740 0.973
0.000 0.000 0.001 0.001 0.000 0.000 0.008 0.102 0.001
ACA indicates anterior carotid artery; MCA, middle cerebral artery; PCA, posterior cerebral artery.
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however, not statistically significant (0.100 < P < 0.943). There were no statistically significant correlations between the arterial diameters measured with CTA and those measured with angiography (Figs. 2–4; Table 3).
DISCUSSION This pilot study is, to our knowledge, the first study that uses a 320-row multidetector CTA in the evaluation of cerebral vasospasm after an ASAH. This is also the first study to adopt a quantitative approach to assess the use of CTA in the evaluation of this condition. All previous studies on this topic have adopted a categorical approach that classifies the degree of severity of cerebral vasospasm into different categories (eg, mild, moderate, and severe) based on radiologic imaging findings.22–28 The advantage of the categorical approach is that, unlike this study, sensitivity, specificity, and positive and negative predictive values can be calculated by comparing the classification obtained from CTA with that obtained from DSA. However, in addition to being less objective, the challenge with these studies is that they almost all use different classification systems, thus making comparison between them challenging. The only exception was Otawara et al29 and Shankar et al,22 who both used the scale of Schneck and Kricheff30 (none, 0% arterial narrowing; mild, 60% arterial narrowing). Chaudhary et al23 used the method from the warfarinAspirin Symptomatic Intracranial Disease Study,24 whereas Yoon et al,25 Anderson et al,26 Binaghi et al,27 and Wintermark et al28 used their own arbitrarily defined scale, with different cutoff values of arterial narrowing to define the different degrees of vasospasm.
FIGURE 2. Anteroposterior view of DSA of the right ICA showing diffuse vasospasm in the supraclinoid ICA (arrowhead), anterior cerebral artery (thick arrow), and the middle cerebral artery (thin arrow). A small saccular aneurysm is seen on top of the unpaired pericallosal artery (asterisk). Figure 2 can be viewed online in color at www.jcat.org.
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FIGURE 3. Axial view of CTA source image of the same patient as in Figure 2. Note the narrowing of the ACA vessels (thick arrows). Figure 3 can be viewed online in color at www.jcat.org.
Allowing for the limitations of CTA, the trend observed within the literature using this discreet approach is that CTA is acknowledged as a valid method to evaluate vasospasm in patients who had an ASAH, with a sensitivity ranging between 63% and 97.5%, a specificity between 90% and 100%, a positive predictive value between 43% and 98.3%, a negative predictive value between 94.1% and 99.5%, and an accuracy between
FIGURE 4. Computer 3-D reconstruction of CTA showing diffuse vasospasm (thick arrows). Figure 4 can be viewed online in color at www.jcat.org. © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Comput Assist Tomogr • Volume 39, Number 4, July/August 2015
320-Row Multidetector CTA for Cerebral Vasospasm
TABLE 3. Arterial Diameters Measured on CTA and DSA Arterial Diameter, mean ± SD, mm Artery Left ICA Right ICA Left ACA Right ACA Left MCA Right MCA Left PCA Right PCA Basilar artery
No. Arteries Included
CTA Measurement
DSA Measurement
7 6 5 8 7 7 4 5 5
2.5807 ± 0.58953 2.7383 ± 0.52190 1.5890 ± 0.48952 1.4019 ± 0.22581 2.0743 ± 0.48584 1.9221 ± 0.26932 1.7650 ± 0.28595 1.8410 ± 0.46790 2.7100 ± 0.51573
3.3000 ± 1.29365 3.0458 ± 0.94953 1.6400 ± 1.29923 1.6250 ± 0.86479 2.0500 ± 1.02713 2.1286 ± 1.09729 1.7250 ± 0.57373 1.5800 ± 0.46449 2.4000 ± 0.62948
ACA indicates anterior carotid artery; MCA, middle cerebral artery; PCA, posterior cerebral artery.
87% and 98%22,23,25–28 (see Table 4). Otawara et al29 did not calculate the sensitivity, specificity, and negative and positive predictive values of CTA in detecting cerebral vasospasm, but have found CTA to be 91.6% accurate. Some of these studies suggest that the sensitivity, specificity, and accuracy of CTA are usually lower in distal vessels than in proximal vessels.22,23,25,26 However, this trend could not be verified in our study because only proximal arterial diameters were measured. Other studies have adopted a quantitative approach similar to the one we adopted to evaluate the accuracy of multidetector CTA, but none have investigated patients in whom cerebral vasospasm was suspected after an ASAH. For instance, Ferguson et al,31 using 4-, 16-, 40-, and 64-row multidetector CTA, compared arterial diameters measurements obtained on CTA with those obtained on DSA in patients with aneurysms. Clinical suspicion of vasospasm was not part of the inclusion criteria. When analyzed as a continuous variable, there was a significant correlation between DSA arterial diameters and corresponding axial CTA images for all the arteries measured (R2 ranging between 0.45 and 0.76, P < 0.0001). It was nevertheless observed that CTA tended to overestimate the arterial narrowing of larger arteries and underestimate the measurement of smaller arteries. This goes in line with the trend observed in this study: in the anterior circulation, arterial diameters seem to be smaller when measured on CTA than on DSA. Based on our initial experience, the degree of inconsistency seems minimal. However, this remains to be proven with a larger sample size. That the same trend could
not be observed in the posterior circulation vessels could be simply explained by greater ease at measuring posterior cerebral circulation on CTA. Interestingly, when Fergusson et al31 divided arterial diameters into different categories (
