Abstract 10227: High-Sensitive Magnetic Particle Imaging of Intraplaque Hemorrhage for Identification of Unstable Atherosclerotic Plaques

Abstract

Introduction: Intraplaque hemorrhage (IPH), which is believed to arise from immature neovessels, drives atherosclerosis progression and is an imaging predictor of stroke and myocardial infarction. However, detection of IPH using magnetic resonance imaging (MRI) might be limited due to false signals from varied plaque components. Magnetic particle imaging (MPI) is a novel tomographic method that directly images the magnetization of ferromagnetic particles. Aims: To test whether MPI can image IPH for detecting unstable plaques and exploring the mechanism of IPH. Methods: The tandem stenosis (TS) mouse model was used to establish unstable plaques with IPH. The intervention agent used for reducing IPH was 4-ABAH. TS ApoE -/- mice and human carotid endarterectomy samples were scanned with MPI and computed tomography. IPH was confirmed by fat-suppressed T1-weighted MRI and Prussian blue staining. Plaque specimens were analyzed histologically. Results: Human carotid samples exhibited endogenous MPI signals, which were related to IPH. Hemosiderin was likely the source of MPI signals. Seven weeks post-TS, unstable plaques in the right carotid artery showed endogenous MPI signals, which were three-fold greater compared with stable plaques in the brachiocephalic artery or normal arterial wall (P < 0.05). From the temporal points, MPI signals in unstable plaques increased from 3.05 ± 1.45 (4 weeks) to 7.29 ± 4.47 (7 weeks) and reduced to 2.59 ± 0.84 (11 weeks) (P < 0.05), while intraplaque neovessel densities showed no difference. Compared with 4 or 7 weeks post-TS, intraplaque neovessels at 11 weeks revealed a more mature phenotype indicated by increased neovessel lumen areas and VE-cadherin (endothelial junction marker) expressions (P < 0.05). Administered 4-ABAH attenuated MPI signals in unstable plaques (9.38 ± 6.75 vs. 3.11 ± 1.25, P < 0.05) and downregulated vWF (endothelial damage marker) expressions (P < 0.05) without affecting neovessel densities or lumen areas. Conclusions: MPI allows ex vivo IPH imaging in human carotid tissues, in vivo IPH monitoring and unstable plaque detection in ApoE -/- mice. MPI-detected IPH is likely associated with endothelial barrier function. As a result, MPI is a promising method for detecting unstable plaques in patients.