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

Abstract

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. 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. 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. 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.