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.


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


  • Cholesterol
  • Gold
  • Integrin alphaVbeta3