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Noninvasive photoacoustic computed tomography/ultrasound imaging to identify high-risk atherosclerotic plaques

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Abstract

Purpose

Noninvasive detection of high-risk plaques is still challenging. In this study, we aimed to noninvasively assess αvβ3-integrin expression using a customed photoacoustic (PA) computed tomography (PACT)/ultrasound (US) system in atherosclerotic lesions of varying degrees of severity and to explore its potential value for detecting high-risk plaques.

Methods

We constructed αvβ3-integrin-targeted ultrasmall gold nanorods (AuNRs) with cyclo Arg-Gly-Asp (cRGD) and tested their properties. Employing C57BL/6 J (wild-type, WT) mice and apolipoprotein E gene knockout (ApoE−/−) mice fed either a chow diet or a high-fat/high-cholesterol diet (HFHCD), we established varying degrees of lesion severity. In vivo PACT/US imaging was performed to assess αvβ3-integrin expression in the 4 groups by cRGD-AuNRs. Further histopathologic examination was conducted to evaluate the plaque vulnerability indicators.

Results

The data showed that cRGD-AuNRs exhibited excellent photothermal conversion capacity, stability, targeting ability, and biocompatibility. The immunohistochemical results indicated that αvβ3-integrin was upregulated with increasing aggravation of the lesions. In vivo PACT/US imaging showed good consistency with αvβ3-integrin expression. Notably, ApoE−/− mice fed a HFHCD showed an abrupt PA intensity increase compared with the other groups. The histopathologic examination verified that the atherosclerotic plaques of ApoE−/− mice fed the HFHCD developed unstable phenotypes. Correlation analysis showed that PA intensity was mainly related to inflammation and angiogenesis among all of the indicators.

Conclusion

Our data indicated that αvβ3-integrin is an effective indicator of plaque instability, and noninvasive PACT/US molecular imaging assessment of αvβ3-integrin holds promise in detecting high-risk plaques.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding authors on reasonable request.

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Acknowledgements

We thank Prof Jianping, Bin and Prof Longquan, Shao for their valuable advice on our manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (No. 81974266, No. 81470598, No.82122034).

Author information

Author notes

  1. Xuewei Liu, Rongkang Gao, Chiyun Chen, These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China

    Xuewei Liu, Xiaobo Li, Chen Yu, Yejia Chen, Hongbin Liang, Min Xiao, Lei Dai, Shifeng Qiu, Xiaoyu Xin & Jiancheng Xiu

  2. Research Laboratory for Biomedical Optics and Molecular Imaging, CAS Key Laboratory of Health Informatics, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China

    Rongkang Gao, Liang Song & Chengbo Liu

  3. Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, Guangdong, China

    Chiyun Chen & Jinbin Liu

Authors
  1. Xuewei Liu
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  2. Rongkang Gao
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  4. Xiaobo Li
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  15. Jiancheng Xiu
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Contributions

Xuewei Liu, Rongkang Gao, and Chiyun Chen designed the research studies, conducted the PACT/US experiments, AuNRs synthesis, analyzed data, and assisted with preparing the manuscript. Xiaobo Li, Chen Yu, and Yejia Chen performed histopathological experiments. Hongbin Liang and Min Xiao analyzes the offline data of PACT/US imaging. Lei Dai, Shifeng Qiu, and Xiaoyu Xin provide reagents. Liang Song provided conceptual and technical advice. Jiancheng Xiu, Chengbo Liu, and Jinbin Liu conceived the idea, designed research studies, conducted experiments, supervised the study, and prepared the manuscript. All authors contributed to the writing and review of the manuscript.

Corresponding authors

Correspondence to Jinbin Liu, Chengbo Liu or Jiancheng Xiu.

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The authors declared no competing interests.

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The animal study protocols were approved by the Nanfang hospital animal ethic committee.

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Liu, X., Gao, R., Chen, C. et al. Noninvasive photoacoustic computed tomography/ultrasound imaging to identify high-risk atherosclerotic plaques. Eur J Nucl Med Mol Imaging 49, 4601–4615 (2022). https://doi.org/10.1007/s00259-022-05911-9

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