Author + information
- Hendrik H.G. Hansen, PhD∗ (, )
- Gert Jan de Borst, MD, PhD,
- Michiel L. Bots, MD, PhD,
- Frans L. Moll, MD, PhD,
- Gerard Pasterkamp, MD, PhD and
- Chris L. de Korte, PhD
- ↵∗Department of Radiology and Nuclear Medicine, Radboud University Medical Center, P.O. Box 9101, Geert Grooteplein-Zuid 10, Nijmegen, Gelderland 6500 HB, the Netherlands
Carotid plaque rupture is a major cause of stroke and mainly occurs in plaques with a substantial necrotic/lipid core, whereas predominantly fibrous plaques are considered to be stable. Presence of local plaque features associated with vulnerability indicates an increased risk of future cerebrovascular events (1) and might serve as a surrogate marker for plaque progression and subsequent cardiovascular events in other vascular beds. To date no patient-friendly, noninvasive, and inexpensive technique for plaque differentiation exists. This is a major limitation, because plaques are often asymptomatic before the first event. Such a technique could also be useful for long-term monitoring to study plaque progression and to determine the effectiveness of treatment on local plaques.
Intravascular palpography imaging revealed a significant correlation between plaque lipid content and radial strain (2). Therefore, we developed a noninvasive technique called compound ultrasound strain imaging (CUSI) (3) which visualizes the radial deformations/strains of the plaque and arterial wall induced by the pulsating blood in transverse imaging planes using radiofrequency ultrasound data acquired at 3 insonification angles. The main advantage of imaging in this plane is the possibility to estimate strains in plaques over the entire cross section instead of only in the anterior and posterior wall. CUSI was validated in phantoms and simulations (3). This study aims at validating CUSI in vivo in patients by relating the measured strains to plaque phenotype derived from histology after carotid endarterectomy.
An experienced ultrasonographer acquired ultrasound radiofrequency data of 34 severely stenotic carotid arteries (>70% stenosis symptomatic [Rankin <3] or >80% asymptomatic) in patients within 48 h prior to endarterectomy at the transverse cross section with the most luminal narrowing (culprit lesion). A Samsung Medison Accuvix V10 with L5-13IS transducer (Samsung, Seoul, South Korea) and a dedicated acquisition mode (radial zone mode) was used to record 3 s of data while electronically switching between insonification angles of 0°, +θ, and -θ (20° ≤ θ ≤ 30°) at a frame rate of ≥129 Hz (43 Hz/angle). Systolic and diastolic blood pressures were determined using a sphygmomanometer. The entire protocol took ∼15 min. The study was approved by the local ethics committee and in accordance with the World Medical Association Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects. All patients agreed to participate and written informed consent was obtained.
Principal strain images representing the deformation component closest aligned with the radial direction from systole to diastole (see the Image of the Month) were calculated offline from the radiofrequency data using compounding and principal component analysis (3,4). In these images yellow and black indicate local wall thickening and thinning, respectively. Strain values were normalized with respect to the measured pulse pressure. A single parameter was defined to characterize the images, the high strain area parameter: the percentage of strain values within a 1 mm thick ring adjacent to the lumen-intima border exceeding 0.5% strain.
After endarterectomy an expert (G.P.) blinded for the strain results classified the phenotype of the culprit lesion segment of the excised plaque following a validated histologic procedure (5). A plaque was classified as fibrous when it had no, or a small lipid core (10% of plaque area), low macrophage infiltration and high smooth muscle cell and collagen content, otherwise it was classified as (fibro)atheromatous.
The Elastin van Gieson–stained histology images and corresponding strain images of the cover figure illustrate that locally elevated strains were observed in atheromatous plaque regions, whereas strains were low for fibrous collagen-rich plaques. Strain parameter values were significantly higher (Mann-Whitney U test, p < 0.01) for (fibro)atheromatous plaques (n = 20; median 55.3% [interquartile range: 44.5% to 67.5%]) compared to fibrous plaques (n = 14; 34.5% [27.8% to 42.4%]), (Figure 1).
A limitation of this study is the relatively small sample size. Furthermore, because CUSI is ultrasound-based, acoustic shadowing impedes strain imaging in heavily calcified plaques. In this study only cases without severe shadowing and which cross section remained in the imaging plane from systole to diastole were included.
To conclude, CUSI was applied successfully in severely stenotic human carotid plaques and strain positively correlated with the presence of an atheromatous core. Because CUSI is relatively inexpensive, noninvasive, and patient-friendly, it might be the first technique to allow screening for vulnerable plaques in earlier (subclinical) stages of atherosclerosis and monitor individual plaque progression over time. Prospective studies such as ECST-2 (European Carotid Surgery Trial 2) have to demonstrate this.
Please note: Dr. de Korte has the same affiliation as the corresponding author and is in charge of the Medical UltraSound Imaging Center (MUSIC). Dr. de Borst is affiliated with the Department of Vascular Surgery of the University Medical Center Utrecht (the Netherlands) which is headed by Dr. Moll. Dr. Bots is in charge of the Julius Center for Health Sciences and Primary Care, and Dr. Pasterkamp is heading the Laboratory of Experimental Cardiology and Laboratory of Clinical Chemistry (research), both are also part of the University Medical Center Utrecht. This research (project number NKG 07589) is supported by the Dutch Technology Foundation (STW), which is part of the Netherlands Organization for Scientific Research (NWO), and is partly funded by the Ministry of Economic Affairs. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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