Combined spatiotemporal and frequency-dependent shear wave elastography enables detection of vulnerable carotid plaques as validated by MRI

Abstract

Fatal cerebrovascular events are often caused by rupture of atherosclerotic plaques. However, ruptureprone plaques are often distinguished by their internal composition rather than degree of luminal narrowing, and conventional imaging techniques might thus fail to detect such culprit lesions. In this feasibility study, we investigate the potential of ultrasound shear wave elastography (SWE) to detect vulnerable carotid plaques, evaluating group velocity and frequency-dependent phase velocities as novel biomarkers for plaque vulnerability. In total, 27 carotid plaques from 20 patients were scanned by ultrasound SWE and magnetic resonance imaging (MRI). SWE output was quantified as group velocity and frequency-dependent phase velocities, respectively, with results correlated to intraplaque constituents identified by MRI. Overall, vulnerable lesions graded as American Heart Association (AHA) type VI showed significantly higher group and phase velocity compared to any other AHA type. A selection of correlations with intraplaque components could also be identified with group and phase velocity (lipid-rich necrotic core content, fibrous cap structure, intraplaque hemorrhage), complementing the clinical lesion classification. In conclusion, we demonstrate the ability to detect vulnerable carotid plaques using combined SWE, with group velocity and frequency-dependent phase velocity providing potentially complementary information on plaque characteristics. With such, the method represents a promising non-invasive approach for refined atherosclerotic risk prediction. Atherosclerotic disease is recognized as a diffuse systemic vascular process, and rupture and erosion of carotid atherosclerotic plaques is the number one cause of cerebrovascular mortality in the world 1. Fatal plaque-related events however often arise without prior symptoms 2 , and the task of plaque risk stratification-identifying rupture-prone vulnerable plaques from stable rupture-resistant phenotypes-is of pivotal clinical importance. Surgical endarterectomy is recommended on the basis of carotid stenosis 3 , however it has been extensively shown that vulnerable plaques are rather identified by their composition than on their extent of luminal obstruction 4,5. Several studies have shown that in the majority of patients with acute ischemic syndromes culprit coronary sites had less than 50-70% diameter narrowing, and plaques producing non-flow-limiting stenosis accounted for more

Vascular Shear Wave Elastography in Atherosclerotic Arteries: A Systematic Review

“…All studies scored an unknown or high risk of bias in at least one category. Seven studies (Ramnarine et al 2014b;Garrard et al 2015;Li et al 2016;Zhang et al 2016;Alis et al 2018;Shang et al 2018;Marlevi et al 2020) did not report whether they included patients randomly or consecutively, and one study reported they did not (Marais et al 2019). In addition, most studies (Li et al 2016;Zhang et al 2016;Lou et al 2017;Marais et al 2019) did not report whether the index test was interpreted without knowledge of the reference standard and vice versa.…”

“…In human studies, push frequencies and imaging rates were not reported, except for an imaging frame rate of 8 kHz by Marais et al (2019). Marlevi et al (2020) applied a dual-sided push pulse of 400 ms simultaneously triggered in the leftand right-hand sides of the region of interest (ROI). Marais et al (2019) applied three supersonic pushes of 100 ms at three depths 5 mm apart along the centerline of the ROI, including the anterior and posterior wall.…”

“…A representative example of a frequently used method of YM assessment with a commercial ultrasound system (Aixplorer Supersonic Imagine) is the method of Ramnarine et al (2014b) with circular ROIs, as illustrated in Figure 1. A representative example of a stateof-the-art non-commercially available implementation of group and phase velocity analysis in the longitudinal and cross-sectional imaging direction using raw ultrasound data is the method of Marlevi et al (2020), illustrated in Figure 2.…”

“…The 10 studies on SWE in human carotid arteries (Ramnarine et al 2014b;Garrard et al 2015;Maksuti et al 2016;Zhang et al 2016;Lou et al 2017;Alis et al 2018;Di Leo et al 2018;Shang et al 2018;Marais et al 2019;Marlevi et al 2020) were performed with varying numbers of patients, that is, 22 (Marlevi et al 2020) to 199 (Zhang et al 2016); different diseases affecting the arterial wall, that is, Behçets disease (Alis et al 2018) and hypertension (Marais et al 2019); and different stages of atherosclerotic disease, that is, atherosclerotic plaques (Ramnarine et al 2014b;Zhang et al 2016;Lou et al 2017;Marlevi et al 2020), symptomatic patients with a CEA scheduled (Garrard et al 2015;Di Leo et al 2018) or without a CEA scheduled (Maksuti et al 2016;Shang et al 2018); and different methods of comparison, that is, pulse wave velocity (PWV) (Maksuti et al 2016;Marais et al 2019) and/or healthy controls (Ramnarine et al 2014b;Maksuti et al 2016;Alis et al 2018;Marais et al 2019) in the arterial wall, and plaque echogenicity (GSM) (Garrard et al 2015;Zhang et al 2016;Lou et al 2017;Shang et al 2018) Because not all patient groups present with atherosclerotic plaques, three studies solely investigated the carotid arterial wall (Maksuti et al 2016;Alis et al 2018;Marais et al 2019). Only one study...…”

“…Only one study (Marais et al 2019) applied echocardiogram (ECG) gating, whereas in the other studies, usually a 10-sec cineloop was recorded and values were averaged over the middle four to five recorded shear wave frames randomly distributed throughout the cardiac cycle. Only Marlevi et al (2020) focused on SWE in the cross-sectional and longitudinal imaging views whereas others investigated SWE only in the longitudinal imaging view.…”