Sensitive Magnetic Particle Imaging of Haemoglobin Degradation for the Detection and Monitoring of Intraplaque Haemorrhage in Atherosclerosis

Background Intraplaque haemorrhage (IPH) drives atherosclerosis progression and is a key imaging biomarker of unstable plaques. Non-invasive and sensitive monitoring of IPH is challenging due to the compositional complexity and dynamic nature of atherosclerotic plaques. Magnetic particle imaging (MPI) is a highly sensitive, radiation-free, and no-tissue-background tomographic technique that detects superparamagnetic nanoparticles. Thus, we aimed to investigate whether MPI can in vivo detect and monitor IPH. Methods Thirty human carotid endarterectomy samples were collected and scanned with MPI. The tandem stenosis (TS) model was employed to establish unstable plaques with IPH in ApoE-/- mice. MPI and 7 T T1-weighted magnetic resonance imaging (MRI) were performed on TS ApoE-/- mice. Plaque specimens were analyzed histologically. Findings Human carotid endarterectomy samples exhibited endogenous MPI signals, which histologically colocalized with IPH. In vitro experiments identified haemosiderin, a haemoglobin degradation product, as a potential source of MPI signals. Longitudinal MPI of TS ApoE-/- mice detected IPH at unstable plaques, of which MPI signal-to-noise ratio values increased from 6.43 +/- 1.74 (four weeks) to 10.55 +/- 2.30 (seven weeks) and reduced to 7.23 +/- 1.44 (eleven weeks). In contrast, 7 T T1-weighted MRI did not detect the small-size IPH (329.91 +/- 226.82 mu m2) at four weeks post -TS. The time-course changes in IPH were shown to correlate with neovessel permeability providing a possible mechanism for signal changes over time. Interpretation MPI is a highly sensitive imaging technology that allows the identification of atherosclerotic plaques with IPH and may help detect and monitor unstable plaques in patients. eBioMedicine 2023;90: Published https://doi.org/10. 1016/j.ebiom.2023. 104509