1 Introduction
Arteriosclerosis, and particularly extracranial atherosclerosis, is a major cause of ischemic cerebrovascular disease.[1–3] [4–7] [8,9]
Magnetic resonance imaging (MRI), an important noninvasive technique, is the preferred examination method in diagnosis of cerebral vascular diseases. Previous studies showed that magnetic resonance angiography (MRA) may over- or underestimate carotid artery stenosis compared with DSA.[10,11] [12] [13] [14–16] [17,18] [19]
In this paper, we developed a concept of quantitative magnetic resonance (QMR) image platform for combing angiography and phase-contrast imaging sequences to provide anatomic visualization and blood flow measurements inside arteries, which can be used for the assessment of luminal stenosis and blood flow changes.[20–22] [23] [12]
The goal of this study was to compare the diagnostic accuracy of QMR with DSA as a gold standard. For patients with unilateral common carotid or internal carotid artery stenosis, CBF of different brain lobes was measured bilaterally to examine changes in the amount of stenosis and to explore the relationship between the symptoms and CBF in different lobes.
2 Methods
This study was a retrospective analysis conducted between January 2014 and April 2016. Sixty-seven patients suspected of having carotid atherosclerotic disease were consecutively enrolled in the study in the first affiliated hospital of Shenzhen University. All patients underwent QMR and DSA sequentially within 2 weeks; QMR imaging included CE-MRA and DSC perfusion imaging. Figure 1 describes criteria for patients’ selection. The examinations were approved by the local medical ethics committee (see graph, Supplemental Content, which demonstrates the agreement of medical ethics committee, https://links.lww.com/MD/B422
Figure 1: The flow diagram illustrating the selection of patients for the study.
DSA was performed when QMR or carotid ultrasound would detect a severe carotid artery stenosis to determine whether the patients should undergo surgery. Exclusion criteria included patients with allergic reaction to contrast medium, severe renal insufficiency (glomerular filtration rates 30 mL/min/1.73 m2 ), and other reasons for which QMR or DSA examination would not be well-tolerated by the patients.
Stenoses were quantified by 2 researchers in a comparable cross-sectional plane on QMR and DSA images. The degree of stenosis was graded according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria[24]
3 Image acquisition
3.1 Quantitative MRA and cerebral blood flow
All examinations were performed on a 1.5-T MR clinical system (Sonata; Siemens, Erlangen, Germany) using head-and-neck coil. All patients underwent routine MR stroke protocol, which included diffusion-weighted imaging (DWI), fluid-attenuated inversion recovery (FLAIR) sequences, PWI, CE-MRA, and DSC perfusion imaging. Contrast injection was performed in 2 phases, without the need for additional contrast. Parameters for the PWI sequence were as follows: repetition time 1410 ms, echo time 30 ms, flip angle 60°, and slice thickness 5 mm; resolution matrix 128 × 128. Parameters for the CE-MRA sequence were as follows: repetition time 3.27 ms, echo time 1.18 ms, flip angle 25°, and slice thickness 1.0 mm; resolution matrix 256 × 192. Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) was used as contrast agent at a dose of 0.1 mmol/kg body weight, administered at a rate of 5 mL/s and flushed with 20 mL of saline for the CE-MRA acquisition. A modified 2-phase contrast injection scheme was used to perform CE-MRA and DSC perfusion imaging, without the need for additional contrast.
DSA imaging was performed within 14 days of the MR examination via femoral artery catheterization by using the digital subtraction technique (Axiom Artis dTA; Siemens, Germany). After inserting a catheter into the artery, 3000 to 5000 U of heparin was injected to prevent blood clotting. Iodinate was used as contrast media in our study. Images were obtained in anteroposterior, lateral, and 2 oblique projections for each catheterization.
3.2 Image evaluation
Two experienced radiologists independently rated all stenoses according to the NASCET criteria for MRA and DSA. Afterwards, 3 researchers (Jingjing Cai, Dan Wu, and Yongqian Mo) revised their ratings and decided on the grades of stenosis using a consensus approach. The researcher of the index tests and reference standard were blinded to the results of QMR and DSA and patients’ basic information. Per-patient and per-vessel stenosis were the maximal stenoses identified in all segments or in all segments within a vessel vicinity, respectively.
3.3 Statistical analyses
Data were analyzed using the software Statistical Package for the Social Sciences (SPSS, version 12.0, Inc., Chicago, IL, USA). Grading of luminal narrowing was compared with DSA as a gold standard. Correlation between QMR and DSA for the assessment of vascular stenosis was calculated using Pearson correlation coefficient. Histograms are used to describe CBF in different lobes for different degrees of stenosis, with or without symptoms. The difference of CBF between the side affected by stenosis and contralateral side was calculated by subtraction (ΔCBF = lesion side − healthy side). P < 0.05 was considered statistically significant.
4 Results
Sixty-seven patients (male 54, female 12) from the first affiliated hospital of Shenzhen University were enrolled from January 2014 and April 2016, and 201 stenoses were detected by QMR and DSA. No motion artifacts affected QMR image quality. The mean age of subjects was 65 ± 8 years ranging from 44 to 79 years. No QMR- and DSA-related adverse events were recorded. Factors associated with artery atherosclerosis were listed in Table 1 : 67.2% of the patients had hypertension and 31.3% had diabetes. Table 2 summarizes the grade of stenosis measured with QMR and DSA. Thirty-three regions of carotid artery were false-positive, and 21 parts were false-negative. Negative predictive values (NPVs) were of 95.71% and positive predictive values (PPVs) were of 89.55%. Overall, false positive rate of QMR was higher than false negative rate. Overestimation occurred in 14 arteries with QMR in which 10 were moderate stenosis (30–69%). In 4 cases of congenital vertebral artery slim, QMR reported moderate to severe stenosis.
Table 1: Basic information of subjects.
Table 2: Comparison of the degree of stenosis with QMR and DSA.
Table 3 lists the stenosis section and degree in stenosis of the artery verified by DSA. Left-side stenosis occurrence rate was slightly higher than the right (55.4% vs 44.6%). In the carotid artery system, internal carotid artery stenosis accounted for 44.1%, which was significantly higher than in other regions. For the measured carotid stenosis degree, scatter plots were drawn to reflect the correlation between QMR and DSA after removing the false positive and negative results. As shown in Fig. 2 A, good correlation was observed between QMR and DSA (r 2 = 0.845). Figure 2 B shows good correlation between QMR and DSA in the length of stenosis, as r 2 = 0.721. Sensitivity and specificity of QMR for detecting severe stenosis was 82.3% and 86.0% with DSA as a 100% reference.
Table 3: Stenosis section and degree on DSA.
Figure 2: Linear regression of CE-MRA and DSA for the stenosis measurement.
The study included 37 patients with unilateral common carotid artery or internal carotid artery stenosis, regardless of the vertebral artery lesions. For these 37 patients, we conducted further analysis of CBF using QMR. In symptomatic group, CBF in frontal, parietal, temporal, and basal ganglia were reduced (Fig. 3 ). Besides, parietal lobes show the most obvious decrease in 4 brain areas and the lowest reduction in the basal ganglia. As compared with asymptomatic group, there was a significant decrease in CBF in temporal and basal ganglia in the symptomatic group.
Figure 3: Comparison of ΔCBF between symptomatic and asymptomatic groups.
To investigate the correlation between the degree of stenosis and Δ CBF, all subjects were divided into 4 groups: Group 1, 1% to 49%, Group 2, 50% to 69%, Group 3, 70% to 99%, and Group 4, 100% (Fig. 4 ). Group 1 included only 2 subjects, and bar charts show that ΔCBF were quite different among brain lobes. For patients with moderate stenosis (50–79%), CBF of ipsilateral frontal lobe was higher than in the contralateral one. However, CBF of parietal, temporal lobes, and basal ganglia was decreased in the ipsilateral side, especially in the basal ganglia. In Group 3 and Group 4, CBF in the ipsilateral hemisphere was reduced in the frontal lobe, parietal lobe, and temporal lobe, while mildly elevated in the basal ganglia.
Figure 4: Comparison of ΔCBF between different grades of stenosis.
5 Discussion
Accurate evaluation of artery stenosis and CBF is essential for guiding clinical treatment. This study suggests that QMR is as accurate and consistent as DSA in measuring artery stenosis. The study presents 3 main findings. First, QMR had a strongest correlation with DSA in the degree and length of stenosis (r 2 = 0.845, 0.721, respectively). Sensitivity and specificity of QMR for detecting severe stenosis was 82.3% and 86.0% with reference to DSA. Second, patients with symptoms had significantly decreased CBF in temporal and basal ganglia. Third, CBF of patients with moderate stenosis (50–79%) in parietal, temporal lobes, and basal ganglia were decreased, while in patients with severe stenosis or occlusion, CBF was mildly elevated in the basal ganglia.
Although DSA is still considered as the gold standard for the evaluation of artery stenosis, there are some limitations to this methodology such as invasiveness that are not easily accepted by patients. Noninvasive imaging techniques such as computed tomography (CT) and MRI have gradually replaced DSA for the diagnosis of carotid artery stenosis. Previously, use of CE-MRA was limited and performed in routine stroke protocols because of its relatively lower spatial resolution and the need for an extra contrast dose. In the last few years, CE-MRA has become required simultaneously to the contrast used for DSC perfusion imaging.[19] [25,26]
In our study, we found that CE-MRA and DSA have a similar efficiency in detecting artery stenosis. Besides, our study confirmed that combining CE-MRA and PWI is feasible and presents no need for additional contrast. Related studies have shown that, compared with other measurements used to measure artery stenosis such as DSA, CT angiography, and ultrasound, QMR angiography provides noninvasive and accurate measurement of all extracranial vessels without exposure to radiotracers.[27,28]
CBF can be measured by a number of imaging techniques, including CT perfusion imaging and PWI. Different imaging techniques have their own advantages and disadvantages.[29] [30]
Previous studies indicated that CVR may be a more accurate predictor of stroke than degree of internal carotid artery or middle cerebral artery stenosis.[31,32] [32] [17] [33]
In our study, the difference value of CBF in bilateral lobes showed nonlinear correlation with the degree of stenosis. We found that patients with severe artery stenosis can maintain CBF at a certain level. Two potential mechanisms may be involved in regulating CBF. On the one hand, as the formation of artery stenosis is a chronic process, the patients with severe stenosis have plenty of time to establish collateral circulation in the case their body is in good condition. On the other hand, adjustment of CBF in different lobes is a dynamic process, so that our body preferentially retains the flow in the regions that are important to preserving vital functions. The results of our study show that CBF of frontal and parietal lobes in patients with severe stenosis decreases significantly.
Our study has several limitations. First, the sample size was relatively small. Further study including a larger sample on patients with different degrees of artery stenosis is therefore needed. Second, although all images were performed on a 1.5-T MR clinical system, more advanced equipment has been used in other studies. Therefore, it is possible that the diagnostic accuracy of QMR will be higher using more advanced scanners. Finally, DSA is considered when moderate to severe vascular disease is diagnosed or when selection of interventional surgery is being considered. The subjects included in our study had relatively severe lesions, which rendered us unable to assess mild stenosis accurately.
6 Conclusions
This study showed good correlation between QMR and DSA in measuring artery stenosis and CBF. Patients with symptoms had a significantly decreased CBF in temporal and basal ganglia. CBF of patients with moderate stenosis in parietal, temporal, and basal ganglia was also decreased, while in patients with severe stenosis or occlusion, CBF was mildly elevated in the basal ganglia. QMR may represent an important method for measuring artery stenosis and cerebral hemodynamics in the future.
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