Cardiac motion artifacts, non-uniform rotational distortion and undersampling affect the image quality and the diagnostic impact of intravascular optical coherence tomography (IV-OCT). In this study we demonstrate how these limitations of IV-OCT can be addressed by using an imaging system that we called “Heartbeat OCT”, combining a fast Fourier Domain Mode Locked laser, fast pullback, and a micromotor actuated catheter, designed to examine a coronary vessel in less than one cardiac cycle. We acquired in vivo data sets of two coronary arteries in a porcine heart with both Heartbeat OCT, working at 2.88 MHz A-line rate, 4000 frames/s and 100 mm/s pullback speed, and with a commercial system. The in vivo results show that Heartbeat OCT provides faithfully rendered, motion-artifact free, fully sampled vessel wall architecture, unlike the conventional IV-OCT data. We present the Heartbeat OCT system in full technical detail and discuss the steps needed for clinical translation of the technology.

Heartbeat OCT: in vivo intravascular megahertz-optical coherence tomography

Accurate and reproducible reconstruction of coronary arteries and endothelial shear stress calculation using 3D OCT: Comparative study to 3D IVUS and 3D QCA

Coronary microvascular dysfunction (CMD) is an increasingly recognized feature of coronary artery disease. We found that progression of CMD in diabetic + hypercholesterolemic swine from 2.5 to 15 m...

Coronary microvascular dysfunction after long-term diabetes and hypercholesterolemia.

The greatest challenge of scientific research is to understand the causes and consequences of disease. In recent years, great efforts have been devoted to unraveling the basic mechanisms of atherosclerosis (the underlying pathology of cardiovascular disease), which remains a major cause of morbidity and mortality worldwide. Because of the complex and multifactorial pathophysiology of cardiovascular disease, different research techniques have increasingly been combined to unravel genetic aspects, molecular pathways, and cellular functions involved in atherogenesis, vascular inflammation, and dyslipidemia to gain a multifaceted picture addressing this complexity. Thanks to the rapid evolution of high-throughput technologies, we are now able to generate large-scale data on the DNA, RNA, and protein levels. With the help of sophisticated computational tools, these data sets are integrated to enhance information extraction and are being increasingly used in a systems biology approach to model biological processes as interconnected and regulated networks. This review exemplifies the use of high-throughput technologies-such as genomics, transcriptomics, proteomics, and epigenomics-and systems biology to explore pathomechanisms of vascular inflammation and atherosclerosis.

The Use of High-Throughput Technologies to Investigate Vascular Inflammation and Atherosclerosis

In the present study, three animal models, including C57BL/6J mice, low-density lipoprotein receptor knockout (LDLR-/-) mice, and rabbit that mimicked atherosclerosis, were established to investigate the inhibitory effect of oleanolic acid (OA) on atherosclerosis. In rabbit model, serum total cholesterol (TC), triglyceride, low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) were measured. Carotid artery lesions were isolated for histological analysis. The red oil O and hematoxylin-eosin staining in liver were examined. The messenger ribonucleicacid (mRNA) levels of PPARγ, AdipoR1, and AdipoR2 related to lipid metabolism were determined. Compared with model group, OA and atorvastatin significantly lowered the levels of TC and LDL-C. The result of red oil O staining showed that OA and atorvastatin had similar effect on reducing the accumulation of lipid. Histological result demonstrated that OA reduced the thickness of intima. AdipoR1 was markedly increased, while AdipoR2 was remarkably decreased in OA group compared with that in the control group of the rabbit model. In LDLR-/- mouse model, lipid parameters in blood and mRNA levels of PPARγ, AdipoR1, and AdipoR2 were measured. It was found that OA exhibited similar effects as atorvastatin including reduced TG, LDL-C, and enhanced HDL-C. Notably, OA elevated the levels of AdipoR1 and PPARγ. At the same time, OA decreased TC and LDL-C in C57BL/6J mice model. Our results in three different animal models all revealed that OA retarded the development of atherosclerosis by influencing serum lipid levels, lipid accumulation in liver and intimal thickening of artery. And the underlying mechanism of OA on atherosclerosis may involve in lipid metabolism genes: PPARγ, AdipoR1, and AdipoR2.

The effects of oleanolic acid on atherosclerosis in different animal models.

Intracoronary Fourier-Domain optical coherence tomography (FD-OCT) enables imaging of the coronary artery within 2-4 seconds, a so far unparalleled speed. Despite such fast data acquisition, cardiac and respiratory motion can cause artefacts due to longitudinal displacement of the catheter within the artery. We studied the influence of longitudinal FD-OCT catheter displacement on serial global lumen and scaffold area measurements in coronary arteries of swine that received PLLA-based bioresorbable scaffolds. In 10 swine, 20 scaffolds (18 × 3.0 mm) were randomly implanted in two epicardial coronary arteries. Serial FD-OCT imaging was performed immediately after implantation (T1) and at 3 (T2) and 6 months (T3) follow-up. Two methods for the selection of OCT cross-sections were compared. Method A did not take into account longitudinal displacement of the FD-OCT catheter. Method B accounted for longitudinal displacement of the FD-OCT catheter. Fifty-one OCT pullbacks of 17 scaffolds were serially analyzed. The measured scaffold length differed between time points, up to one fourth of the total scaffold length, indicating the presence of longitudinal catheter displacement. Between method A and B, low error was demonstrated for mean area measurements. Correlations between measurements were high: R2 ranged from 0.91 to 0.99 for all mean area measurements at all time points. Considerable longitudinal displacement of the FD-OCT catheter was observed, diminishing the number of truly anatomically matching cross-sections in serial investigations. Global OCT dimensions such as mean lumen and scaffold area were not significantly affected by this displacement. Accurate co-registration of cross-sections, however, is mandatory when specific regions, e.g. jailed side branch ostia, are analyzed.

The impact of Fourier-Domain optical coherence tomography catheter induced motion artefacts on quantitative measurements of a PLLA-based bioresorbable scaffold

Experimental disease models have enhanced our understanding of the pathogenesis of atherosclerosis development. For example, insight has been gained into the role of the endothelium, lipids, platelets and inflammation, as well as into potential diagnostic and therapeutic interventions. Moreover, transgenic and knock-out technologies have become a widespread approach and this is a growing field to assess the role of individual genes in vascular biology and pathology. However, atherosclerosis is most of all a multifactorial disease, influenced by a multitude of environmental factors. Therefore, it is important to also study non-transgenic animal models that closely resemble the human situation with atherosclerotic lesions at anatomical locations that mimic the clinical manifestation of the disease, e.g. coronary artery disease (CAD). Although no model completely mimics human atherosclerosis, much can be learned from existing models in the study of this disease, also with respect to the development of new interventions. Here, we describe the most relevant animal models of atherosclerosis, while focusing on CAD development and the use of coronary diagnostic and therapeutic interventions. In addition, we show examples of features of a large animal model of CAD including pictures of invasive coronary imaging.

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M.M. Van Den Heuvel

Papers

The impact of Fourier-Domain optical coherence tomography catheter induced motion artefacts on quantitative measurements of a PLLA-based bioresorbable scaffold

Invasive coronary imaging in animal models of atherosclerosis