Sensitive magnetic particle imaging of haemoglobin degradation for the detection and monitoring of intraplaque haemorrhage in atherosclerosisResearch in context
Wei Tong,
Yingqian Zhang,
Hui Hui,
Xin Feng,
Bin Ning,
Tengfei Yu,
Wei Wang,
Yaxin Shang,
Guanghao Zhang,
Suhui Zhang,
Feng Tian,
Wen He,
Yundai Chen,
Jie Tian
Affiliations
Wei Tong
Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, China; CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China
Yingqian Zhang
Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, China
Hui Hui
CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; Beijing Key Laboratory of Molecular Imaging, Beijing, 100190, China; University of Chinese Academy of Sciences, Beijing, 100080, China
Xin Feng
CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; Beijing Key Laboratory of Molecular Imaging, Beijing, 100190, China; University of Chinese Academy of Sciences, Beijing, 100080, China
Bin Ning
Department of Ultrasound, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China
Tengfei Yu
Department of Ultrasound, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China
Wei Wang
Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, China
Yaxin Shang
School of Computer and Information Technology, Beijing Jiaotong University, Beijing, 100069, China
Guanghao Zhang
CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China
Suhui Zhang
Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, China
Feng Tian
Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, China
Wen He
Department of Ultrasound, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China; Corresponding author. Department of Ultrasound, Beijing Tiantan Hospital, Capital Medical University, No.119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, China.
Yundai Chen
Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, China; Corresponding author. Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital, No. 6 Fucheng Road, Hai Dian District, Beijing, 100048, China.
Jie Tian
CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; Beijing Key Laboratory of Molecular Imaging, Beijing, 100190, China; Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology of China, Beijing, 100191, China; Zhuhai Precision Medical Center, Zhuhai People's Hospital, Affiliated with Jinan University, Zhuhai, 519000, China; Corresponding author. CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, No. 95 Zhongguancun East Road, Hai Dian District, Beijing, 100190, China.
Summary: 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 μm2) 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. Funding: This work was supported in part by the Beijing Natural Science Foundation under Grant JQ22023; the National Key Research and Development Program of China under Grant 2017YFA0700401; the National Natural Science Foundation of China under Grant 62027901, 81827808, 81730050, 81870178, 81800221, 81527805, and 81671851; the CAS Youth Innovation Promotion Association under Grant Y2022055 and CAS Key Technology Talent Program; and the Project of High-Level Talents Team Introduction in Zhuhai City (Zhuhai HLHPTP201703).
