Abstract
Background
Computed tomography angiography (CTA) is increasingly used for non-invasive imaging of the cerebrovascular diseases.
Purpose
To evaluate the accuracy of CTA in the assessment of the variation of the segment calibers of the circle of Willis.
Material and Methods
One hundred and 17 patients with acute SAH (51 men and 66 women, mean age 50.9 years) who underwent CTA using a 16 detector-row CT scanner and DSA were evaluated retrospectively. The CTA and DSA studies were performed within 24 h after the onset of symptoms and within 24 h of each other. A total of 819 arterial segments (A-comA, right and left A1 segment, right and left P-com A, and right and left P1 segment) of the circle of Willis were determined to be aplastic (grade 1), hypoplastic (grade 2), or normal-sized (grade 3) by blinded observers evaluating CTA volume-rendered images. The CTA results were then compared with findings on the corresponding DSA images (reference standard).
Results
The overall agreement between CTA and DSA was 92.4%. We had 62 (7.6%) cases of disagreement (58 cases of under-estimation and four cases of over-estimation by CTA) between tow modalities. The sensitivity and specificity of CTA in the detection of aplastic and normal-sized segments were more than 90%. In contrast, subgroup analysis of the hypoplastic segments showed a sensitivity of 52.6% and a specificity of 98.2%.
Conclusion
CTA is highly accurate in the assessment of anatomical variations of the circle of Willis; however, its sensitivity is limited in depicting hypoplastic segments.
Keywords
The circle of Willis is a polygonal structure composed of the A1 segments of anterior cerebral arteries (ACAs), anterior communicating artery (A-comA), P1 segments of posterior cerebral arteries (PCAs), posterior communicating arteries (P-comAs) (1). The circle is an important potential pathway that maintains adequate blood flow in case of various steno-occlusive disease (2), but variations (hypoplasia or aplasia) of the arterial segments are common (3, 4). In addition, the circle of Willis is the site of the majority of intracerebral aneurysms. The patency and size of the arteries in the circle of Willis is important in the planning of surgical clipping or endovascular coiling in certain cases of aneurysm.
Digital subtraction angiography (DSA) is considered the standard of reference for assessment of the anatomy of the circle of Willis (5). This procedure, however, is invasive and is not always available in critically-ill patients and not without its inherent risk (6, 7). With advance of multidetector-row computed tomography (CT) scanners, computed tomography angiography (CTA) is increasingly used for non-invasive imaging of the cerebrovascular diseases, including aneurysms (8), vasospasm (9), and steno-occlusive lesions (10).
However, to our knowledge, only one report (11) reported the accuracy of CTA in the analysis of the circle of Willis. The aim of the study was to retrospectively evaluate the accuracy of CTA in assessing the variation of the segment calibers of the circle of Willis compared with DSA in patients with acute subarachnoid hemorrhage (SAH).
Material and Methods
Patients
Our institutional review board approved this study, and informed consent was waived as the patients' data were evaluated retrospectively and anonymously.
From March 2004 through August 2010, 124 consecutive patients, with acute SAH confirmed by unenhanced CT or lumbar puncture, who underwent both CTA and DSA within 24 h after the onset of symptoms and within 24 h of each other, were included in this study. Of them, five patients with arterial occlusions or severe stenoses in the internal carotid artery (ICA) or proximal segment of ACA/middle cerebral artery (MCA)/PCA were excluded because intracranial hemodynamics might be altered in these patients. One patient who had undergone prior surgical clipping or endovascular coiling for treatment of aneurysm was excluded as well because it could not completely be ruled out that cerebral blood flow dynamics might be affected in such a patient. One patient was excluded because of pronounced motion artifacts interfering with diagnostic decision-making.
Thus, our final study population consisted of 117 patients; this group included 51 men and 66 women (mean age 50.9 years ± 12.4, range 23–84 years).
All patients underwent CTA before DSA, with the mean interval between the two examinations being 6.2 hours ± 6.3.
CTA protocol
All CTA examinations were performed with a 16 detector-row CT scanner (MX8000 Infinite Detector Technology; Philips, Haifa, Israel) with the following parameters: 1-mm section thickness; 0.5-second gantry rotation time; pitch of 0.35; 512 × 512 matrix; 20–22-cm field of view; and 120 kV and 200–280 mA. The effective dose of CTA was calculated to be 14.1 mSv. The scanning range was planned in a caudocranial direction from the level of the foramen magnum through a point 1 cm above the level of the lateral ventricles, including whole circle of the Willis (mean coverage 80 mm, range 75–85 mm). For optimal intraluminal contrast enhancement, the delay time between start of contrast material administration and start of scanning was determined for each patient individually by using a bolus-tracking technique. A total of 60–100 mL of iohexol (Omnipaque 300; GE Healthcare, Princeton, NJ, USA) was administered through an 18- or 20-gauge needle positioned in a peripheral vein. The contrast material was administered with a power injector at a rate of 3–4 mL/s.
The volumetric data so obtained were transferred to a workstation with commercially available software (RAPIDIA 3D; Infinitt, Seoul, Korea) for further processing. Transverse sections were reconstructed with a section width of 0.5 mm. CTA images were processed from the obtained source images by using two different methods: (a) volume-rendered technique (VRT) algorithm; and (b) VRT images after automatic segmentation of a precontrast scan data-set (i.e. any overlapping bony structures, calcification, and surgical materials). All acquired images were transferred to a picture archiving and communication system workstation (Pi-ViewStar, Infinitt) for analysis.
DSA
All DSA was performed transfemorally with a DSA unit (Integris Allura; Philips Medical Systems, Best, The Netherlands) with an image intensifier matrix of 1024 × 1024 pixels. DSA was performed with bilateral selective ICA injections and either unilateral or bilateral vertebral artery injections. Anteroposterior, lateral, and if necessary oblique view(s) of each vessel were obtained by the injection of 6–9 mL of iodixanol (Visipaque 320; GE Healthcare, Princeton, NJ, USA). Additional ICA angiograms were also obtained with compression of the contralateral carotid artery in cases in which the A-comA was not visible on routine DSA images.
Image analysis
All CTA and DSA images were independently evaluated on the workstations by two radiologists, who had 14 (DYY) and 7 (SKC) years of experience in cerebral CTA and DSA. Each examination was allocated a study number that was known only to the study coordinator (ARH). Both readers were blinded to the assessments of the other modality or of the other investigator. The CTA and DSA images were reviewed separately: DSA images were given in random order to readers, 8 weeks after each reader completed the analysis of CTA images. After independent assessment, the CTA and DSA studies where there was interpretation disagreement between two readers were reviewed jointly for a final consensus.
For analysis purposes, the arteries of the circle of Willis were separately evaluated as seven anatomic segments on CTA and DSA images: A-comA, right and left A1 segments of ACAs, right and left P-comAs, and right and left P1 segments of PCAs. All measures were performed on the workstation with an electronic caliper after appropriate magnification. Each segment was assigned one of three categories: grade 1, aplasia (no flow); grade 2, hypoplasia (≥ 50% luminal narrowing); and grade 3, normal size. Reference diameter of hypoplasia was the diameter of non-diseased ipsilateral proximal P2 segment for P-comA and P1 and mean diameter of A2 segments for A-comA and A1. There was no case with arterial segments duplication in the circle of Willis.
The CTA and DSA examinations were compared for each arterial segment using Spearman correlation coefficient. Sensitivity, specificity, positive and negative predictive values, and accuracy of CTA for determination of aplasia, hypoplasia or normal size were calculated using DSA as standard of reference.
Results
In 117 patients, a total of 819 arterial segments were analyzed on both CTA and DSA images. Overall, DSA depicted 551 normal-sized, 78 hypoplastic, and 190 aplastic arterial segments. The most frequently seen variant was aplasia of the P-comA, which was present in 124 (53.0%) of 234 segments. At DSA, a total of 106 aneurysms was present in 98 of the 117 patients involved in the study; six patients had two aneurysms and one patient had three aneurysms. Of these aneurysms, 62 (58.5%) were located at the circle of Willis (35 A-comA and 27 P-comA aneurysms).
The number of arterial segments determined to be aplastic, hypoplastic, or normal-sized on each of the imaging techniques is summarized in Table 1. The overall agreement between CTA and DSA for all locations and types was 92.4%, with a Spearman correlation coefficient of 0.9551. In examining the data for P-comAs, we found poorer degree of agreement and correlation than for the other segments. We had 62 (7.6%) of 819 segments of disagreement between CTA and DSA. CTA showed a clear trend to underestimate the arterial segments compared to DSA. The arterial segments were underestimated by one grade in 50 segments and by two grades in eight segments (Fig. 1). There were only four segments with over-estimation at CTA (all by one grade).
A 39-year-old woman presented with SAH due to rupture of a left P-comA aneurysm (arrowhead in b and d). Anteroposterior view DSA images of the right (a) and left (b) ICA and the left vertebral artery (c) reveal the complete circle of Willis. Note normal-sized right A1 segment (arrows in a and b). (d) Superior projection VRT CTA image shows the same configuration of the circle of Willis except A1 segment of the right ACA. The right A1 segment (arrows) was graded as hypoplastic (underestimated by CTA)
Arterial segments of the circle of Willis: assessment by CT angiography as compared with digital subtraction angiography in 117 patients
Data are number of segments; data in parentheses are percentages
DSA = digital subtraction angiography; CTA = CT angiography; A-comA = anterior communicating artery; A1 = first segment of anterior cerebral artery (between origin and the A-comA); P-comA = posterior communicating artery; P1 = first segment of posterior cerebral artery (between origin and the P-comA)
*r = Spearman correlation coefficient
Table 2 summarizes the sensitivity, specificity, positive and negative predictive values, and accuracy of CTA for the detection of aplastic, hypoplastic, and normal-sized segments. The sensitivity and specificity of CTA in the detection of normal-sized and aplastic segments were more than 90%. In contrast, subgroup analysis of the hypoplastic segments showed a sensitivity of 52.6% and a specificity of 98.2%.
Diagnostic performance of CT angiography compared with digital subtraction angiography in assessment of arterial segments of the circle of Willis
PPV = positive predictive value; NPV = negative predictive value
Discussion
It is well established that considerable variations exists in the circle of Willis (3, 4). Segmental aplasias and hypoplasias are common and most commonly involve the P-comAs (12, 13).
In the present study, with the use of VRT algorithm, the overall agreement between CTA and DSA was 92.4% in the assessment of anatomical variations of the circle of Willis. However, the agreement rate was lower for the P-com As (84.2%); 37 (59.7%) of the 62 segments of disagreement between the two modalities were the P-com As. Our results showed that CTA against DSA resulted in 58 segments of under-estimation and four segments of over-estimation in the assessment of the circle of Willis. The under-estimation of arterial segments with CTA may be explained by the lower image resolution of CTA than DSA. In addition, some cases of under-estimation were likely to be due to collateral vessels opacified from the systemic injection of contrast at CTA. Although DSA is the gold standard for the assessment of collateral flow, the forced arterial injection of contrast and local increases in arterial pressure may cause changes in arterial diameter (14). Four segments (2 P-comAs and 2 P1 segments) with over-estimation at CTA in this series may be explained by the superimposition of basal veins or adjacent arteries (the anterior choroidal artery or the superior cerebellar artery), especially in the posterior circulation.
Although our study demonstrated acceptable (> 90%) agreement, sensitivity, and specificity values for CTA as compared with DSA, the sensitivity of CTA for depicting hypoplastic segments was poor (52.6%).
Several previous studies (5, 11) have demonstrated that CTA is an accurate technique to assess a fetal origin of the PCA (P-comA larger than P1 segment). However, we found in the literature only one article assessing the diagnostic accuracy of CTA in the evaluation of the circle of Willis. Skutta et al. (11) compared the combined both maximum-intensity projection (MIP) and source images of double-detector CTA with DSA in 112 patients with suspected cerebrovascular disease. The authors focused on the steno-occlusive lesions, therefore, no comprehensive analyses of anatomic variants were made. In their study, of 703 arterial segments revealed by DSA, 527 were seen with MIP (sensitivity 75%) and 584 were seen on source images (sensitivity 83%); the specificity was, however, not reported.
Magnetic resonance angiography (MRA) is another non-invasive technique that can demonstrate the configuration of the circle of Willis (15–17). Previous studies (15, 18–20) have demonstrated that the overall sensitivity of MRA was acceptable (higher than 80%) in depicting the presence or absence of arterial segments of the circle of Willis. However, their specificity of MRA (63–100%) varied according to the MRA techniques and analysis methods used. A recently published study (20) comparing MRA (3D time-of-flight [TOF] and 2D phase contrast images) and DSA found that collateral flow measurements via the anterior part of the circle of Willis yielded sensitivity and specificity of 83% and 77%, respectively. However, the sensitivity of MRA was very low (33%) for the P-comA.
Although 3D TOF MRA is widely used in the diagnosis of intracranial aneurysms and cerebral steno-occlusive diseases, the technique is not without limitations. Because the sensitivity of MRA is dependent on the blood flow velocity, the technique may have difficulties in visualizing small vessels in the circle of Willis with slow or turbulent flows (3, 21). In addition, laminar flow-related spin dephasing and partial volume averaging at the vessel wall may result in a reduction of the vessel diameter, which lead to under-estimation of the vessel on the source images and MIP algorithm (19, 22).
In contrast, CTA is not dependent on the flow velocity, thereby allowing accurate documentation of vessel diameters. The disadvantages of CTA compared to MRA include the lack of information regarding flow direction, possible venous contamination, radiation exposure, and administration of iodinated contrast material.
We acknowledge several limitations of our study. First, there is still uncertainty about the definition of hypoplastic vessels forming the circle of Willis. Several previous workers have used different sets of criteria to define hypoplasia. They have stated that a vessel with a diameter of smaller than 0.8 mm (3, 23) or 1 mm (24, 25) would be considered hypoplastic. In this study, however, accurate measurement of vessel diameter was not possible on DSA images because the magnification factor was not calculated. Therefore, we compared diameters of the segments with those of the distal arteries on both CTA and DSA, instead of absolute values of the measurements. Second, another possible problem in our study relates to the fact that we used only VRT algorithms to assess the circle of Willis. For accurate assessment of vascular status with CTA, it is important to review 3D images as well as the axial source images. Results of a previous CTA study (11) showed that combining 3D (MIP) images and axial source data improved the visibility of small vessels. Third, this study had only patients with SAH. Therefore, vasospasm following SAH may have hampered correct evaluation of the circle of Willis in our patients. However, cerebral vasospasm rarely occurs before the fourth day and reaches a peak around the seventh day after onset of the SAH (26). In all our patients, CTA and DSA were performed within 48 h after onset of SAH and with the mean interval between the two examinations being 6.2 h; therefore, we expect only a minor effect on the accuracy.
In conclusion, the results of this study show that CTA is highly accurate in the assessment of anatomical variations of the circle of Willis. However, CTA has limited sensitivity in depicting hypoplastic segments, although it remains quite specific.