Abstract
Cardiovascular disease entails systemic changes in the vasculature. The endothelial cells lining the blood vessels are crucial in the pathogenesis of cardiovascular disease. Healthy endothelial cells direct the blood flow to tissues as vasodilators and act as the systemic interface between the blood and tissues, supplying nutrients for vital organs, and regulating the smooth traffic of leukocytes into tissues. In cardiovascular diseases, when inflammation is sensed, endothelial cells adjust to the local or systemic inflammatory state. As the inflamed vasculature adjusts, changes in the endothelial cells lead to endothelial dysfunction, altered blood flow and permeability, expression of adhesion molecules, vessel wall inflammation, thrombosis, angiogenic processes, and extracellular matrix production at the endothelial cell level. Preclinical multi-scale imaging of these endothelial changes using optical, acoustic, nuclear, MRI, and multimodal techniques has progressed, due to technical advances and enhanced biological understanding on the interaction between immune and endothelial cells. While this review highlights biological processes that are related to changes in the cardiac vasculature during cardiovascular diseases, it also summarizes state-of-the-art vascular imaging techniques. The advantages and disadvantages of the different imaging techniques are highlighted, as well as their principles, methodologies, and preclinical and clinical applications with potential future directions. These multi-scale approaches of vascular imaging carry great potential to further expand our understanding of basic vascular biology, to enable early diagnosis of vascular changes and to provide sensitive diagnostic imaging techniques in the management of cardiovascular disease.
Highlights
Cardiovascular disease (CVD) is the leading cause of death worldwide and is associated with several chronic diseases and adverse health outcomes
It was shown that 18F-Macroflor, a modified nanoparticle with high avidity for macrophages, was enriched in cardiac and plaque macrophages. This enabled the sensitive tracking of macrophages in a positron emission tomography (PET)/magnetic resonance imaging (MRI) study of the infarcted heart in both mice and rabbits [61]
This review attempted to clarify, illustrate, and expound on multi-scale imaging technologies applied to visualize endothelial cell alterations appearing during the pathogenesis of CVDs
Summary
Cardiovascular disease (CVD) is the leading cause of death worldwide and is associated with several chronic diseases and adverse health outcomes. Through the quantification of endogenous myocardial T1, the leakage of albumin-conjugated contrast agents, extravasating through permeable myocardial blood vessels, was monitored on short axis cardiac MR images These permeability measurements identified high vascular permeability in the infarcted region compared to remote regions in the heart 3 days post-infarct (Figures 3I,J). This enabled the sensitive tracking of macrophages in a PET/MRI study of the infarcted heart in both mice and rabbits [61] Another multimodal strategy was recently implemented and applied to quantify 89Zr-labeled liposomal nanoparticle uptake in the atherosclerotic vessel wall of rabbits using PET, in conjunction with CT and DCEMRI with low-molecular Gd-DTPA for vascular permeability. In vivo multimodal imaging was performed using MRI/PET/SPECT techniques to detect and visualize vascular injury and thrombogenic plaque in mice using 64Cu-labeled glycoprotein VI-Fc 64Cu-GPVI-Fc contrast agent. Changes in ECM content during infarct healing and plaque development, provide potential targets for non-invasive assessment of plaque burden and cardiac outcome
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