Jonathan H. Gillard

Coronary Plaque Structural Stress Is Associated With Plaque Composition and Subtype and Higher in Acute Coronary Syndrome The BEACON I (Biomechanical Evaluation of Atheromatous Coronary Arteries) Study

Background—Atherosclerotic plaques underlying most myocardial infarctions have thin fibrous caps and large necrotic cores; however, these features alone do not reliably identify plaques that rupture. Rupture occurs when plaque structural stress (PSS) exceeds mechanical strength. We examined whether PSS could be calculated in vivo based on virtual histology (VH) intravascular ultrasound and whether PSS varied according to plaque composition, subtype, or clinical presentation. Methods and Results—A total of 4429 VH intravascular ultrasound frames from 53 patients were analyzed, identifying 99 584 individual plaque components. PSS was calculated by finite element analysis in whole vessels, in individual plaques, and in higher-risk regions (plaque burden ≥70%, mean luminal area ⩽4 mm2, noncalcified VH-defined thin-cap fibroatheroma). Plaque components including total area/arc of calcification (R2=0.33; P<0.001 and R2=0.28; P<0.001) and necrotic core (R2=0.18; P<0.001 and R2=0.15; P<0.001) showed complex, nonlinear relationships with PSS. PSS was higher in noncalcified VH-defined thin-cap fibroatheroma compared with thick-cap fibroatheromas (median [Q1–Q3], 8.44 [6.97–10.64] versus 7.63 [6.37–9.68]; P=0.002). PSS was also higher in patients with an acute coronary syndrome, where mean luminal area ⩽4 mm2 (8.24 [7.06–9.93] versus 7.72 [6.33–9.34]; P=0.03), plaque burden ≥70% (9.18 [7.44–10.88] versus 7.93 [6.16–9.46]; P=0.02), and in noncalcified VH-defined thin-cap fibroatheroma (9.23 [7.33–11.44] versus 7.65 [6.45–8.62]; P=0.02). Finally, PSS increased the positive predictive value for VH intravascular ultrasound to identify clinical presentation. Conclusions—Finite element analysis modeling demonstrates that structural stress is highly variable within plaques, with increased PSS associated with plaque composition, subtype, and higher-risk regions in patients with acute coronary syndrome. PSS may represent a novel tool to analyze the dynamic behavior of coronary plaques with the potential to improve prediction of plaque rupture.

Inflammation and Neovascularization Intertwined in Atherosclerosis: Imaging of Structural and Molecular Imaging Targets

Atherosclerosis is a chronic inflammatory disease characterized by lipid-containing inflammatory lesions of large- and medium-sized arteries. It is primarily a disease of the inner layer of the arterial wall, the intima. As the disease advances, the adventitia, however, also participates in the pathogenesis of the atherosclerosis. Herrmann et al1 have proposed that the development of human atherosclerotic lesions can be considered to involve 3 distinct stages. In the first stage, early alterations in cellular function result from the interaction of environmental risk factors and genetic predisposition. The second stage is characterized by the proliferation of adventitial vasa vasorum with subsequent extension of the neovessels into the inner media and eventually into the enlarging plaque. In vulnerable plaques, vessel density increases from 2- to 4-fold in disrupted plaques, compared with several obstructive stable lesions. Chronic lesions can enter the third stage with further neovascularization, especially in the vulnerable shoulder areas of the plaques. At this stage, the intraplaque neovessels may rupture, leading to intraplaque hemorrhage. This may be because of compromised integrity of the microvascular endothelium and plaque weakening secondary to inflammation. The exacerbation of tightly intertwined plaque inflammatory activity and neovascularization results in plaque rupture, leading to arterial thrombosis with ensuing clinical syndromes.nnRevolution in the field of radiology in the last 3 decades has enabled imaging of inflammation and neovascularization within atherosclerotic tissue. In this article, we review advances in various clinical and preclinical imaging modalities aimed at unraveling the pathobiology of atherosclerosis.nnThe use of ultrasound (US) for molecular imaging of the cardiovascular system is an extension of contrast echocardiographic principles already in clinical use. Nontargeted US contrast agents (UCAs) act purely as intravascular blood tracers behaving as red blood cells within the microcirculation. Targeted UCAs decorated with ligands, by affinity-based interaction, localize to a site where …

Material properties of components in human carotid atherosclerotic plaques: A uniaxial extension study

Graphical abstract Fibrous cap and media in the carotid atherosclerotic plaques are much stiffer than either lipid, intraplaque haemorrhage or thrombus.

Plaque hemorrhage in carotid artery disease: Pathogenesis, clinical and biomechanical considerations

Stroke remains the most prevalent disabling illness today, with internal carotid artery luminal stenosis due to atheroma formation responsible for the majority of ischemic cerebrovascular events. Severity of luminal stenosis continues to dictate both patient risk stratification and the likelihood of surgical intervention. But there is growing evidence to suggest that plaque morphology may help improve pre-existing risk stratification criteria. Plaque components such a fibrous tissue, lipid rich necrotic core and calcium have been well investigated but plaque hemorrhage (PH) has been somewhat overlooked. In this review we discuss the pathogenesis of PH, its role in dictating plaque vulnerability, PH imaging techniques, marterial properties of atherosclerotic tissues, in particular, those obtained based on in vivo measurements and effect of PH in modulating local biomechanics.

Optimization of Improved Motion-sensitized Driven-equilibrium (iMSDE) blood suppression for carotid artery wall imaging

BackgroundImproved motion-sensitized driven-equilibrium (iMSDE) preparations have been successfully used in carotid artery wall imaging to achieve blood suppression, but it causes notable signal loss, mostly due to inherent T2 decay, eddy current effects and B1+ inhomogeneity. In this study, we investigate the signal to noise ratio (SNR) and blood suppression performance of iMSDE using composite RF pulses and sinusoidal gradients. Optimized first moment (m1) values for iMSDE prepared T1- and T2- weighted (T1- and T2-w) imaging are presented.MethodsTwelve healthy volunteers and six patients with carotid artery disease underwent iMSDE and double inversion recovery (DIR) prepared T1- and T2-w fast spin echo (FSE) MRI of the carotid arteries. Modified iMSDE module using composite RF pulses and sinusoidal gradients were evaluated with a range of m1. SNR of adjacent muscle, vessel wall and the lumen were reported. The optimized iMSDE module was also tested in a 3D variable flip angle FSE (CUBE) acquisition.ResultsThe SNR of muscle was highest using sinusoidal gradients, and the relative improvement over the trapezoidal gradient increased with higher m1 (p<0.001). Optimal SNR was observed using an iMSDE preparation scheme containing two 180° composite pulses and standard 90° and -90° pulses (p=0.151). iMSDE produced better blood suppression relative to DIR preparations even with a small m1 of 487 mT*ms2/m (p<0.001). In T1-w iMSDE, there was a SNR decrease and an increased T2 weighting with increasing m1. In T2-w iMSDE, by matching the effective echo time (TE), the SNR was equivalent when m1 was <= 1518 mT*ms2/m, however, higher m1 values (2278 – 3108 mT*ms2/m) reduced the SNR. In the patient study, iMSDE improved blood suppression but reduced vessel wall CNR efficiency in both T1-w and T2-w imaging. iMSDE also effectively suppressed residual flow artifacts in the CUBE acquisition.ConclusionsiMSDE preparation achieved better blood suppression than DIR preparation with reduced vessel wall CNR efficiency in T1-w and T2-w images. The optimized m1s are 487 mT*ms2/m for T1-w imaging and 1518 mT*ms2/m for T2-w imaging. Composite 180° refocusing pulses and sinusoidal gradients improve SNR performance. iMSDE further improves the inherent blood suppression of CUBE.

The influence of computational strategy on prediction of mechanical stress in carotid atherosclerotic plaques: Comparison of 2D structure-only, 3D structure-only, one-way and fully coupled fluid-structure interaction analyses

Background Compositional and morphological features of carotid atherosclerotic plaques provide complementary information to luminal stenosis in predicting clinical presentations. However, they alone cannot predict cerebrovascular risk. Mechanical stress within the plaque induced by cyclical changes in blood pressure has potential to assess plaque vulnerability. Various modeling strategies have been employed to predict stress, including 2D and 3D structure-only, 3D one-way and fully coupled fluid-structure interaction (FSI) simulations. However, differences in stress predictions using different strategies have not been assessed. Methods Maximum principal stress (Stress-P1) within 8 human carotid atherosclerotic plaques was calculated based on geometry reconstructed from in vivo computerized tomography and high resolution, multi-sequence magnetic resonance images. Stress-P1 within the diseased region predicted by 2D and 3D structure-only, and 3D one-way FSI simulations were compared to 3D fully coupled FSI analysis. Results Compared to 3D fully coupled FSI, 2D structure-only simulation significantly overestimated stress level (94.1 kPa [65.2, 117.3] vs. 85.5 kPa [64.4, 113.6]; median [inter-quartile range], p=0.0004). However, when slices around the bifurcation region were excluded, stresses predicted by 2D structure-only simulations showed a good correlation (R2=0.69) with values obtained from 3D fully coupled FSI analysis. 3D structure-only model produced a small yet statistically significant stress overestimation compared to 3D fully coupled FSI (86.8 kPa [66.3, 115.8] vs. 85.5 kPa [64.4, 113.6]; p<0.0001). In contrast, one-way FSI underestimated stress compared to 3D fully coupled FSI (78.8 kPa [61.1, 100.4] vs. 85.5 kPa [64.4, 113.7]; p<0.0001). Conclusions A 3D structure-only model seems to be a computationally inexpensive yet reasonably accurate approximation for stress within carotid atherosclerotic plaques with mild to moderate luminal stenosis as compared to fully coupled FSI analysis.

Imaging Carotid Atherosclerosis Plaque Ulceration: Comparison of Advanced Imaging Modalities and Recent Developments

SUMMARY: Atherosclerosis remains the leading cause of long-term mortality and morbidity worldwide, despite remarkable advancement in its management. Vulnerable atherosclerotic plaques are principally responsible for thromboembolic events in various arterial territories such as carotid, coronary, and lower limb vessels. Carotid plaque ulceration is one of the key features associated with plaque vulnerability and is considered a notable indicator of previous plaque rupture and possible future cerebrovascular events. Multiple imaging modalities have been used to assess the degree of carotid plaque ulceration for diagnostic and research purposes. Early diagnosis and management of carotid artery disease could prevent further cerebrovascular events. In this review, we highlight the merits and limitations of various imaging techniques for identifying plaque ulceration.

3D high-resolution contrast enhanced MRI of carotid atheroma--a technical update.

OBJECTIVEnDevelopment of a fast 3D high-resolution magnetic resonance imaging (MRI) protocol for improved carotid artery plaque imaging.nnnMETHODSnTwo patients with carotid atherosclerosis disease underwent 3D high-resolution MRI which included time-of-flight and T1-weighted variable flip angle, fast-spin-echo (FSE) imaging, pre- and post-intravenous gadolinium-based contrast agent administration.nnnRESULTSnGood quality images with intrinsic blood suppression were obtained pre- and post-contrast administration using a 3D FSE sequence. The plaque burden, lipid core volume, hemorrhage volume and fibrous cap thickness were well determined.nnnCONCLUSIONSn3D high-resolution MR imaging of carotid plaque using TOF and 3D FSE can achieve high isotropic resolution, large coverage, and excellent image quality within a short acquisition time.

Three-dimensional black-blood T2 mapping with compressed sensing and data-driven parallel imaging in the carotid artery

PURPOSEnTo develop a 3D black-blood T2 mapping sequence with a combination of compressed sensing (CS) and parallel imaging (PI) for carotid wall imaging.nnnMATERIALS AND METHODSnA 3D black-blood fast-spin-echo (FSE) sequence for T2 mapping with CS and PI was developed and validated. Phantom experiments were performed to assess T2 accuracy using a Eurospin Test Object, with different combination of CS and PI acceleration factors. A 2D multi-echo FSE sequence was used as a reference to evaluate the accuracy. The concordance correlation coefficient and Bland-Altman statistics were calculated. Twelve volunteers were scanned twice to determine the repeatability of the sequence and the intraclass correlation coefficient (ICC) was reported. Wall-lumen sharpness was calculated for different CS and PI combinations. Six patients with carotid stenosis >50% were scanned with optimised sequence. The T2 maps were compared with multi-contrast images.nnnRESULTSnPhantom scans showed good correlation in T2 measurement between current and reference sequence (r=0.991). No significant difference was found between different combination of CS and PI accelerations (p=0.999). Volunteer scans showed good repeatability of T2 measurement (ICC: 0.93, 95% CI 0.84-0.97). The mean T2 of the healthy wall was 48.0±9.5ms. Overall plaque T2 values from patients were 54.9±12.2ms. Recent intraplaque haemorrhage and fibrous tissue have higher T2 values than the mean plaque T2 values (88.1±6.8ms and 62.7±9.3ms, respectively).nnnCONCLUSIONnThis study demonstrates the feasibility of combining CS and PI for accelerating 3D T2 mapping in the carotid artery, with accurate T2 measurements and good repeatability.

Influence of material property variability on the mechanical behaviour of carotid atherosclerotic plaques: a 3D fluid-structure interaction analysis.

Mechanical analysis has been shown to be complementary to luminal stenosis in assessing atherosclerotic plaque vulnerability. However, patient-specific material properties are not available and the effect of material properties variability has not been fully quantified. Media and fibrous cap (FC) strips from carotid endarterectomy samples were classified into hard, intermediate and soft according to their incremental Youngs modulus. Lipid and intraplaque haemorrhage/thrombus strips were classified as hard and soft. Idealised geometry-based 3D fluid-structure interaction analyses were performed to assess the impact of material property variability in predicting maximum principal stress (Stress-P1) and stretch (Stretch-P1). When FC was thick (1000 or 600 µm), Stress-P1 at the shoulder was insensitive to changes in material stiffness, whereas Stress-P1 at mid FC changed significantly. When FC was thin (200 or 65 µm), high stress concentrations shifted from the shoulder region to mid FC, and Stress-P1 became increasingly sensitive to changes in material properties, in particular at mid FC. Regardless of FC thickness, Stretch-P1 at these locations was sensitive to changes in material properties. Variability in tissue material properties influences both the location and overall stress/stretch value. This variability needs to be accounted for when interpreting the results of mechanical modelling.