Molecular Magnetic Resonance Imaging of Myeloperoxidase Activity Identifies Culprit Lesions and Predicts Future Atherothrombosis

Overview

Journal Eur Heart J Imaging Methods Pract

Specialty Cardiology & Vascular Diseases

Date 2024 Feb 19

PMID 38370393

Authors

James Nadel

Xiaoying Wang

Prakash Saha

Andre Bongers

Sergey Tumanov

Nicola Giannotti

Weiyu Chen

Niv Vigder

Mohammed M Chowdhury

Gastao Lima da Cruz

Carlos Velasco

Claudia Prieto

Andrew Jabbour

Rene M Botnar

Roland Stocker

Alkystis Phinikaridou

Affiliations

Soon will be listed here.

Abstract

Aims: Unstable atherosclerotic plaques have increased activity of myeloperoxidase (MPO). We examined whether molecular magnetic resonance imaging (MRI) of intraplaque MPO activity predicts future atherothrombosis in rabbits and correlates with ruptured human atheroma.

Methods And Results: Plaque MPO activity was assessed in rabbits ( = 12) using the MPO-gadolinium (Gd) probe at 8 and 12 weeks after induction of atherosclerosis and before pharmacological triggering of atherothrombosis. Excised plaques were used to confirm MPO activity by liquid chromatography-tandem mass spectrometry (LC-MSMS) and to determine MPO distribution by histology. MPO activity was higher in plaques that caused post-trigger atherothrombosis than plaques that did not. Among the MRI metrics, the plaques' R1 relaxation rate after administration of MPO-Gd was the best predictor of atherothrombosis. MPO activity measured in human carotid endarterectomy specimens ( = 30) by MPO-Gd-enhanced MRI was correlated with patient MRI and histological plaque phenotyping, as well as LC-MSMS. MPO-Gd retention measured as the change in R1 relaxation from baseline was significantly greater in histologic and MRI-graded American Heart Association (AHA) type VI than type III-V plaques. This association was confirmed by comparing AHA grade to MPO activity determined by LC-MSMS.

Conclusion: We show that elevated intraplaque MPO activity detected by molecular MRI employing MPO-Gd predicts future atherothrombosis in a rabbit model and detects ruptured human atheroma, strengthening the translational potential of this approach to prospectively detect high-risk atherosclerosis.

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