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

Xuewei Liu; Rongkang Gao; Chiyun Chen; Xiaobo Li; Chen Yu; Yejia Chen; Hongbin Liang; Min Xiao; Lei Dai; Shifeng Qiu; Xiaoyu Xin; Liang Song; Jinbin Liu; Chengbo Liu; Jiancheng Xiu

doi:10.1007/s00259-022-05911-9

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

Eur J Nucl Med Mol Imaging. 2022 Nov;49(13):4601-4615. doi: 10.1007/s00259-022-05911-9. Epub 2022 Jul 23.

Authors

Xuewei Liu^#¹, Rongkang Gao^#², Chiyun Chen^#³, Xiaobo Li¹, Chen Yu¹, Yejia Chen¹, Hongbin Liang¹, Min Xiao¹, Lei Dai¹, Shifeng Qiu¹, Xiaoyu Xin¹, Liang Song², Jinbin Liu⁴, Chengbo Liu⁵, Jiancheng Xiu⁶

Affiliations

¹ Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
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.
³ Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, Guangdong, China.
⁴ Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, Guangdong, China. cejbliu@scut.edu.cn.
⁵ 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. cb.liu@siat.ac.cn.
⁶ Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China. xiujch@163.com.

^# Contributed equally.

PMID: 35870006
DOI: 10.1007/s00259-022-05911-9

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.

Keywords: Gold nanorods; High-risk atherosclerotic plaque; Molecular imaging; Photoacoustic computed tomography; αvβ3-integrin.

MeSH terms

Animals
Cholesterol / metabolism
Gold
Integrin alphaVbeta3 / metabolism
Macrophages / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout, ApoE
Plaque, Atherosclerotic* / diagnostic imaging
Plaque, Atherosclerotic* / metabolism
Tomography, X-Ray Computed
Ultrasonography

Substances

Cholesterol
Gold
Integrin alphaVbeta3