Key result
A non-invasive, quantitative MRI workflow was developed to measure arterial endothelial damage (leakiness and dysfunction) in atherosclerotic mice, with potential for clinical translation.
Why the study?
Reproducible and simple approaches for extracting quantifiable data reflective of endothelial damage from a single imaging study in vivo were needed.
A novel, non-invasive quantitative MRI workflow enables the in vivo assessment of endothelial permeability and dysfunction in atherosclerotic models, with potential for clinical translation.
Novel MRI method may detect early endothelial dysfunction; leaves open its clinical utility and reproducibility.
Cardiovascular diseases are the leading causes of death worldwide. A permeable/leaky and dysfunctional endothelium is considered the earliest marker of vascular damage and thought to drive atherosclerosis. A method to identify these changes in vivo would be desirable in the clinic. Magnetic resonance imaging (MRI)-based tools and other technologies have enabled a profound understanding of the role of the endothelium in cardiovascular diseases and risk in vivo. There is, however, a need for reproducible and simple approaches for extracting quantifiable data reflective of endothelial damage from a single imaging study. A non-invasive, easy-to-implement, and quantitative MRI workflow was developed to acquire and analyze images that allow the quantification of two imaging biomarkers of arterial endothelial damage (leakiness/permeability and dysfunction). Here, the protocol describes the application of this method in the brachiocephalic artery of atherosclerotic ApoE-/- mice using a clinical MRI scanner. First, late gadolinium enhancement (LGE) and Modified Look-Locker Inversion Recovery (MOLLI) T1 mapping protocols to quantify endothelial leakage using an albumin-binding probe are described. Second, anatomic, and quantitative blood flow sequences to measure endothelial dysfunction, in response to acetylcholine are described. Importantly, the method outlined here allows the acquisition of high-spatial-resolution 3D images with large volumetric coverage enabling accurate segmentation of vessel wall structures to improve inter- and intra-observer variability and to increase reliability and reproducibility. Additionally, it provides quantitative data without the need for high-temporal resolution for complex kinetic modeling, making it model-independent and even allowing for imaging of highly mobile vessels (coronary arteries). Therefore, the approach simplifies and expedites data analysis. Finally, this method can be implemented on different scanners, can be extended to image different arterial beds, and is clinically applicable for use in humans. This method could be used to diagnose and treat patients with atherosclerosis by adopting a precision-medicine approach.
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Lavín et al. (2021) studied Atherosclerosis. Quantitative MRI workflow was evaluated on Quantification of endothelial leakage and dysfunction. A non-invasive, quantitative MRI workflow was developed to measure arterial endothelial damage (leakiness and dysfunction) in atherosclerotic mice, with potential for clinical translation.
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