In vivo temperature heterogeneity is associated with plaque regions of increased MMP-9 activity

Krams, Rob; Verheye, Stefan; Damme, Luc C.A. van; Tempel, Dennie; Gourabi, Babak Mousavi; Boersma, Eric; Kockx, Mark; Knaapen, Michiel; Strijder, Chaylendra; Langenhove, Glenn Van; Pasterkamp, Gérard; Steen, A.F.W. van der; Serruys, Patrick W.

doi:10.1093/eurheartj/ehi461

Cited by 31 publications

(18 citation statements)

References 28 publications

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“…In addition, we performed a detailed error analysis of the 3-D histology approach developed for coregistering WSS metrics from CFD to histological data, which demonstrated a circumferential error of 265 μm and an axial error of 340 μm that represent a significant improvement to previous reports from both others [6][7][8]12,23,24 and ourselves. [25][26][27][28][29] Importantly, this 3-D histology error analysis included the assessment of the reproducibility of identification of the same vessel segment of interest from the FD-OCT images through time. Therefore, it accounts for small changes in vessel size that may occur over time owing to remodeling or acquisition of the FD-OCT at different average positions within the cardiac cycle (see Methods in the online-only Data Supplement).…”

Section: Discussionmentioning

confidence: 99%

Inducing Persistent Flow Disturbances Accelerates Atherogenesis and Promotes Thin Cap Fibroatheroma Development in D374Y -PCSK9 Hypercholesterolemic Minipigs

et al. 2015

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C oronary heart disease is projected to remain the worldwide leading cause of death until 2030.1 Coronary heart disease is a major cause of morbidity and reduced quality of life with enormous economic consequences.2,3 Atherosclerosis, a multifocal lipid-driven inflammatory process, is the principal underlying pathology in patients with coronary heart disease, which commonly presents clinically with symptoms secondary to luminal narrowing of an epicardial coronary artery or Background-Although disturbed flow is thought to play a central role in the development of advanced coronary atherosclerotic plaques, no causal relationship has been established. We evaluated whether inducing disturbed flow would cause the development of advanced coronary plaques, including thin cap fibroatheroma. Methods and Results-D374Y-PCSK9 hypercholesterolemic minipigs (n=5) were instrumented with an intracoronary shear-modifying stent (SMS). Frequency-domain optical coherence tomography was obtained at baseline, immediately poststent, 19 weeks, and 34 weeks, and used to compute shear stress metrics of disturbed flow. At 34 weeks, plaque type was assessed within serially collected histological sections and coregistered to the distribution of each shear metric. The SMS caused a flow-limiting stenosis, and blood flow exiting the SMS caused regions of increased shear stress on the outer curvature and large regions of low and multidirectional shear stress on the inner curvature of the vessel. As a result, plaque burden was ≈3-fold higher downstream of the SMS than both upstream of the SMS and in the control artery (P<0.001). Advanced plaques were also primarily observed downstream of the SMS, in locations initially exposed to both low (P<0.002) and multidirectional (P<0.002) shear stress. Thin cap fibroatheroma regions demonstrated significantly lower shear stress that persisted over the duration of the study in comparison with other plaque types (P<0.005). Conclusions-These data support a causal role for lowered and multidirectional shear stress in the initiation of advanced coronary atherosclerotic plaques. Persistently lowered shear stress appears to be the principal flow disturbance needed for the formation of thin cap fibroatheroma. an acute coronary syndrome. The latter is a major cause of coronary heart disease death and most commonly results from rupture at the site of a thin cap fibroatheroma (TCFA) leading to coronary thrombosis. 4The precise environmental cues that lead plaques toward an advanced and high-risk phenotype are not yet fully elucidated, but disturbed blood flow is thought to play a central role in both lesion initiation and progression.5 Disturbed flow is most frequently quantified by metrics of shear stress, which is the frictional force imposed by blood flowing over the endothelial surface, and association between these metrics and coronary atherosclerotic lesion stage have been demonstrated in vivo in both animal models 6-9 and patients. 10,11 However, few studies have investigated the impact of prevalent shear co...

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Section: Discussionmentioning

confidence: 99%

Inducing Persistent Flow Disturbances Accelerates Atherogenesis and Promotes Thin Cap Fibroatheroma Development in D374Y -PCSK9 Hypercholesterolemic Minipigs

et al. 2015

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“…Most of the preliminary development of algorithms for the detection and characterization of atherosclerotic plaques is performed using animal models of disease. 6,24,25 It is possible that because of the biological differences that exist between animals and humans, the different tissue types contained in animal atherosclerotic lesions may not be similar to the lesions seen in human disease. However, distinct histological patterns such as the formation of fibrotic tissue or fibro-lipidic tissue do not differ much between species, and many other catheter-based technologies have been validated on the detection of these specific components in porcine models of disease.…”

Section: Granada Et Al In Vivo Animal Validation Of Ivus-vh 389mentioning

confidence: 99%

In Vivo Plaque Characterization Using Intravascular Ultrasound–Virtual Histology in a Porcine Model of Complex Coronary Lesions

Granada

Wallace-Bradley

Win

et al. 2007

ATVB

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Objective-To determine the accuracy of detection of different tissue types of intravascular ultrasound-virtual histology (IVUS-VH) in a porcine model of complex coronary lesions. Methods and Results-Coronary lesions were induced by injecting liposomes containing human oxidized low-density lipoprotein into the adventitia of the arteries. IVUS-VH imaging was performed in vivo at 8.2Ϯ1.6 weeks after injection. A total of 60 vascular lesions were analyzed and compared with their correspondent IVUS-VH images. Correlation analysis was performed using linear regression models. Key Words: animal model Ⅲ intravascular ultrasound Ⅲ vulnerable plaque C omplex atherosclerotic plaques containing specific morphological features appear to be responsible for the majority of major coronary events. 1-4 Therefore, the accurate identification and characterization of these lesions has become one of the major challenges of interventional cardiology. 5 Several catheter-based imaging devices designed and built to characterize such features are currently undergoing development. 6 -10 Mainly because of the lack of a large animal model of atherosclerotic vascular disease, the initial development of these technologies is based on the construction of mathematical algorithms based on data acquired from ex vivo evaluation of postmortem human arterial specimens. Therefore, the translation of these algorithms of detection into an in vivo setting may not be universally accurate.Virtual histology is an intravenous ultrasound (IVUS)-based technology that studies the spectral analysis of the radio frequency signals backscattered from the plaque during IVUS imaging and reconstructs the morphology of the plaque through color-coded maps. 11 Although this technique has been validated in vitro and ex vivo in human coronary arteries [11][12][13][14] and preliminary clinical experience has been published, 15,16 little data have been published on histological correlates of images acquired in vivo. 17 In the present study, we describe the histological characteristics of complex coronary lesions analyzed in vivo using intravascular ultrasoundvirtual histology (IVUS-VH) in a porcine model of disease.

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“…2,8,9 OCT has been shown to be able to visualize macrophages in vivo without the use of contrast agents, 10 but there is some controversy regarding this claim because the OCT features that identify the macrophages could also be caused by calcium or other plaque constituents. 11 A few other techniques are being developed with the aim of providing the functional imaging capabilities of molecular imaging without the use of contrast agents: thermography is a nonlabeling intravascular technique that has been shown to be capable of recognizing temperature heterogeneity in regions of plaque with high inflammation and MMP activity 12 and intravascular catheters for near infrared and Raman spectroscopy are being developed that would allow for measurements of the biochemical composition of plaque. 2 Recent studies also demonstrated that autofluorescence features of atherosclerotic plaques could be used to intravascularly characterize plaque composition without the use of contrast agents.…”

Section: Introductionmentioning

confidence: 99%

Fluorescence lifetime imaging for the characterization of the biochemical composition of atherosclerotic plaques

et al. 2011

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Abstract. This study investigates the ability of a flexible fiberoptic-based fluorescence lifetime imaging microscopy (FLIM) technique to resolve biochemical features in plaque fibrotic cap associated with plaque instability and based solely on fluorescence decay characteristics. Autofluorescence of atherosclerotic human aorta (11 autopsy samples) was measured at 48 locations through two filters, F377: 377/50 and F460: 460/60 nm (center wavelength/bandwidth). The fluorescence decay dynamic was described by average lifetime (τ ) and four Laguerre coefficients (LECs) retrieved through a Laguerre deconvolution technique. FLIM-derived parameters discriminated between four groups [elastin-rich (ER), elastin and macrophage-rich (E+M), collagenrich (CR), and lipid-rich (LR)]. For example, τ F377 discriminated ER from CR (R = 0.84); τ F460 discriminated E+M from CR and ER (R = 0.60 and 0.54, respectively); LEC-1 F377 discriminated CR from LR and E+M (R = 0.69 and 0.77, respectively); P < 0.05 for all correlations. Linear discriminant analysis was used to classify this data set with specificity >87% (all cases) and sensitivity as high as 86%. Current results demonstrate for the first time that clinically relevant features (e.g., ratios of lipid versus collagen versus elastin) can be evaluated with a flexible-fiber based FLIM technique without the need for fluorescence intensity information or contrast agents. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

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In vivo temperature heterogeneity is associated with plaque regions of increased MMP-9 activity

Abstract: In vivo temperature measurements enable to detect plaques that contain more macrophages, less SMCs, and a higher MMP-9 activity.

Cited by 31 publications

References 28 publications

Inducing Persistent Flow Disturbances Accelerates Atherogenesis and Promotes Thin Cap Fibroatheroma Development in D374Y -PCSK9 Hypercholesterolemic Minipigs

Inducing Persistent Flow Disturbances Accelerates Atherogenesis and Promotes Thin Cap Fibroatheroma Development in D374Y -PCSK9 Hypercholesterolemic Minipigs

In Vivo Plaque Characterization Using Intravascular Ultrasound–Virtual Histology in a Porcine Model of Complex Coronary Lesions

Fluorescence lifetime imaging for the characterization of the biochemical composition of atherosclerotic plaques

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