Assessment of carotid atherosclerotic disease using three-dimensional cardiovascular magnetic resonance vessel wall imaging: comparison with digital subtraction angiography

Carotid atherosclerosis is increasingly recognized as the leading cause of ischemic stroke [1‐3]. Previous studies have shown that accurate evaluation of the degree of carotid stenosis would be beneficial for predicting the risk of stroke [4‐6]. Digital subtraction angiography (DSA) is still considered the clinical gold standard for assessing the severity of carotid atherosclerosis [7, 8]. However, several major limitations of DSA have impeded its widespread use in routine imaging workups, including invasiveness and potential complications, radiation exposure, high costs, and difficulty in visualizing lesions with positive remodeling [9, 10]. As a result, DSA is typically reserved for surgical interventions [7]. In contrast, ultrasound is a relatively cheap and portable method, and has been widely used for first-line diagnosis of atherosclerosis. However, ultrasound is susceptible to the level of experience of operators, and the use for patients with short, muscular necks is limited [11]. In contrast, high-resolution black-blood (BB) cardiovascular magnetic resonance (CMR) imaging can non-invasively visualize and quantify the vessel lumen and wall at a relatively low cost and without radiation exposure [12‐16]. Hence, many groups have incorporated BB CMR in order to facilitate the diagnosis of carotid artery disease [17‐21].

Recently, a three-dimensional (3D) CMR vessel wall imaging (VWI) technique based on 3D T1 weighted (T1w) Sampling Perfection with Application-optimized Contrast using different flip-angle Evolutions (SPACE) has become technically feasible and gained increasing attention for the diagnosis of atherosclerosis [22‐26]. This technique is advantageous over conventional two-dimensional techniques, as it has sufficient BB effects, large spatial coverage, high isotropic resolution and signal-to-noise ratio (SNR), excellent scan efficiency, and remarkable cerebrospinal fluid (CSF) signal attenuation [23, 24, 27]. It therefore shows a unique capability for evaluating both lumen and wall features. Zhang et al. [27] demonstrated the reliability (excellent intra- and inter-observer agreement and scan-rescan reproducibility) of the 3D whole-brain intracranial VWI technique for quantifying intracranial vessel dimensions in 34 healthy subjects and 10 patients with known intracranial atherosclerotic disease. However, the diagnostic accuracy of 3D CMR VWI with respect to the luminal features involved in atherosclerosis has not been systematically validated against the clinical gold standard. Thus, we aimed to evaluate the performance of the 3D CMR VWI modality in diagnosing intra- and extra-cranial carotid atherosclerosis, using DSA as a reference.

This study protocol was approved by the local Institutional Review Board of Beijing Anzhen Hospital (Capital Medical University, Beijing, China). Written informed consents were obtained from either the patients or their legal representatives prior to study entry.

This study confirms the accuracy of the 3D CMR VWI technique based on the 3D T1w SPACE sequence for the diagnosis of carotid atherosclerosis, particularly the assessment of various luminal features, in symptomatic patients with ≥50% carotid artery stenosis. We found that the 3D CMR VWI technique is highly consistent with DSA when measuring the lumen diameter of the CCA and segments C1-C7 segments, as well as the stenosis diameter, stenosis degree, and reference diameter. Additionally, this technique showed excellent accuracy for diagnosing total occlusion, ulcerative lesions, and moderate to severe stenosis. Hence, our results justify the increasing use of 3D CMR VWI as a reliable, accurate, and non-invasive imaging modality for diagnosing carotid artery disease.

Analysis of inter-observer reproducibility is an essential requirement for validation of an imaging modality. Zhang et al. [27] previously performed a comprehensive reliability analysis for the 3D whole-brain CMR VWI technique. However, this study was limited by the small sample size of clinical patients. In our study, two experienced radiologists evaluated the intra- and extra-cranial carotid walls using 3D CMR VWI in 65 patients. Our results showed excellent inter-observer reproducibility for measurement of the lumen diameter of the CCA and segments C1-C7 of the carotid artery, stenosis diameter, stenosis degree, and reference diameter. There were systematic differences in diameter measurements, particularly at large-size vessel segments, between reader 1 and 2. This may be due to the different measurement habits among readers and non-circular lumen shapes of the large-size segments. Nevertheless, these differences were all submillimeters and not clinically relevant for diagnosis. Thus, 3D CMR VWI is considered to be a reliable imaging modality for the quantification of luminal morphologic features.

In this study, we evaluated the agreement between 3D CMR VWI and DSA. The morphologic measurements, including the lumen diameter of the CCA and segments C1-C7, and the stenosis diameter, stenosis degree, reference diameter, and lesion length, as measured by 3D CMR VWI, displayed excellent accordance with those measured by DSA (ICC > 0.84). One possible reason for the excellent performance of the 3D CMR VWI technique is that a non-selective excitation radio-frequency pulse has been used to shorten the echo time, which helps improve the SNR of images [23, 24, 27]. Additionally, 3D CMR VWI provided a high isotropic resolution of 0.63 × 0.63 × 0.63 mm³, and achieves good flexibility with regard to image visualization, which thereby enables the visualization of plaques located in the tortuous and deep-seated intracranial carotid. Furthermore, dedicated CSF signal suppression is implemented in this technique, which can help to visualize the outer boundaries of the vessel wall [23, 27].

However, our study showed some systematic differences between CMR VWI and DSA. Firstly, the lumen diameter tended to be underestimated by VWI at larger sized vessel segments. This discrepancy might be caused by the underlying differences in image acquisition and measurement. Specifically, DSA is a projection-based imaging modality and the distance between two parallel vessel boundaries from the imaging perspective is inherently the largest possible diameter of the vessel from that perspective. However, diameter measurement on VWI is performed from reformatted cross-sectional images and derived by averaging two perpendicular hand-drawn straight-line distances. Either of these lines is necessarily aligned with the DSA perspective, and more importantly, each distance may not represent the true diameter at that angle if the straight line misses the lumen center, thus underestimating the diameter. The averaging procedure would further make the measured diameter smaller, particularly at larger vessel segment that are not necessarily round. Secondly, the lesion lengths measured by 3D CMR VWI are about 3 mm longer than those measured by DSA in arteries with > 50% stenosis. The potential reason may be the distal portion of a wedge-shaped plaque being regarded as the reference on DSA [33, 34].

In our study, 3D CMR VWI showed a poor ability to identify pseudo-occlusion and small ulcerations (width < 1.5 mm), compared with DSA. Mistaking pseudo-occlusion for total occlusion on 3D CMR VWI might be explained by the fact that DSA has much better spatial and temporal resolution than 3D CMR VWI. This is in line with the findings of a previous study [20]. Missing small ulceration is attributed not only to the poorer spatial resolution but also to the existence of tiny calcification in the surface of the lumen [12, 20]. Therefore, we should pay more attention to the irregular calcification on the 3D CMR VWI images so as to detect ulceration properly. A previous study showed that bright-blood sequences are highly accurate in the detection of ulcerations because of a good depiction of the luminal boundary. Therefore, future studies which examine the combination of bright-blood sequences with 3D T1w SPACE sequences for the comprehensive diagnosis of ulceration are warranted [35].

Zhao et al. [20] performed a study similar to the current one, and showed that 3D BB MR imaging could accurately diagnose patients with moderate to severe carotid artery stenosis, which is consistent with the findings of our study. One potential limitation of their study is that they only assessed the consistency and accuracy of 3D BB MR in carotid lesions with > 50% stenosis. However, an increasing number of studies have found that carotid lesions with low-grade stenosis may also lead to stroke [4‐6]. Moreover, cerebral angiography is often required before carotid artery stent implantation in order to observe the intracranial Willis ring opening and cerebral blood flow perfusion. Therefore, our study performed a comprehensive analysis of the consistency and accuracy of 3D CMR VWI in lesions with both less than and greater than 50% stenosis. We showed excellent consistency for measurement of lumen diameter and stenosis in all arteries between 3D CMR VWI and DSA. However, CMR VWI may be less accurate for more severe lesions. Briefly, there are two potential reasons why this may be the case. First, 3D CMR VWI has poorer spatial resolution than DSA, meaning that the measurement errors induced by partial volume effect become more evident in cases of severe stenoses. Second, blood signal suppression may become more challenging as the severity of stenosis increases, resulting in residual flow artifacts particularly at juxta-luminal locations. Another limitation of their study was that they only assessed lesions located at the level of carotid bifurcation and not segments C2-C7, whilst carotid atherosclerosis is a pan-vascular disease involving intra- and extra- cranial arteries. 3D CMR VWI images can cover the whole internal carotid artery within 7 min. Assessment of lesions within a large FOV is useful for the selection of stent size and the formulation of surgical procedures [36].

There were several limitations in this study. Firstly, measurements of 3D CMR VWI were acquired using MPR. Therefore, discrepancy from mismatched slices of the carotid artery lesions between 3D CMR VWI and DSA may have compromised the agreement analysis. Secondly, 3D CMR VWI was still susceptible to motion and residual blood flow artifacts which occurred at certain anatomical locations, including carotid bifurcations and petrous and lacerum segments of ICAs, which can interfere with the correct assessment of the condition [22]. For example, 3D CMR VWI reader 1 misdiagnosed 6 artifacts as stenosis in our study. Thirdly, CMR angiography was not included in our imaging protocol. There were two main reasons for this design. First, our study primarily aimed to evaluate the diagnostic performance of 3D CMR VWI in characterizing carotid disease by comparison with the clinical gold standard (DSA), but not to focus on the agreement analysis between 3D CMR VWI and MRA. Second, carotid CMR angiography acquired by time-of-flight (TOF) or contrast-enhanced gradient recalled echo (GRE) typically has a much lower spatial resolution than 3D CMR VWI (isotropic 0.63 mm).

3D CMR VWI can be used to accurately assess carotid atherosclerosis with high spatial resolution and large anatomical coverage in a single scan, suggesting that the imaging modality may serve in routine imaging workup with comprehensive information for both the vessel wall and lumen.