Inflammation is a pivotal driver of atherosclerotic plaque progression and rupture and is a target for identifying vulnerable plaques. However, challenges arise with the current
in vivo
imaging modalities for differentiating vulnerable atherosclerotic plaques from stable plaques due to their low specificity and sensitivity. Herein, we aimed to develop a novel multimodal imaging platform that specifically targets and identifies high-risk plaques
in vivo
by detecting active myeloperoxidase (MPO), a potential inflammatory marker of vulnerable atherosclerotic plaque.
Methods:
A novel multimodal imaging agent, 5-HT-Fe
3
O
4
-Cy7 nanoparticles (5HFeC NPs), used for active MPO targeting, was designed by conjugating superparamagnetic iron oxide nanoparticles (SPIONs) with 5-hydroxytryptamine and cyanine 7 N-hydroxysuccinimide ester. The specificity and sensitivity of 5HFeC NPs were evaluated using magnetic particle imaging (MPI), fluorescence imaging (FLI), and computed tomographic angiography (CTA) in an ApoE
-/-
atherosclerosis mouse model. Treatment with 4-ABAH, an MPO inhibitor, was used to assess the monitoring ability of 5HFeC NPs.
Results:
5HFeC NPs can sensitively differentiate and accurately localize vulnerable atherosclerotic plaques in ApoE
-/-
mice
via
MPI/FLI/CTA. High MPI and FLI signals were observed in atherosclerotic plaques within the abdominal aorta, which were histologically confirmed by multiple high-risk features of macrophage infiltration, neovascularization, and microcalcification. Inhibition of active MPO reduced accumulation of 5HFeC NPs in the abdominal aorta. Accumulation of 5HFeC NPs in plaques enabled quantitative evaluation of the severity of inflammation and monitoring of MPO activity.
Conclusions:
This multimodal MPI approach revealed that active MPO-targeted nanoparticles might serve as a method for detecting vulnerable atherosclerotic plaques and monitoring MPO activity.
The 9.41GHz ferromagnetic resonance field and linewidth have been measured as a function of the angle (θH) between the external magnetic field and film normal for a series of 17.5nm thick Co–Cr–Pt alloy films. The linewidths ranged from hundreds of Oersted to kiloersted, with different values at θH=0 and θH=90° and additional minima and maxima for θH-values from 16° to 64°. The profiles can be fitted with a combination of inhomogeneity line broadening, grain boundary two magnon scattering, and magnon-electron (m-e) scattering processes, with a notably small Gilbert damping α-value of 0.004 for the m-e term.
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