Abstract Current diagnostic technique in direct identification of multi‐site plaques and simultaneous assessment of plaque vulnerability remains a challenge, which is crucial for indicating the risk of atherosclerotic cardiovascular diseases (ASCVD). Herein, an osteopontin (OPN)‐specific nanoprobe (OPN Ab‐Au/FeNiPO 4 @ICG) with both multiple spectra optoacoustic tomography (MSOT) and computed tomography (CT) imaging, is constructed successfully realizing systemic screening of vulnerable plaque. OPN Ab‐Au/FeNiPO 4 @ICG nanoprobe specifically targeted OPN‐overexpressed foam cells and recognized the vulnerable plaque at the molecular level. In AS mice, CT imaging exhibits that OPN Ab‐Au/FeNiPO 4 @ICG nanoprobe effectively avoid interference from calcification and accurately visualized AS plaque. MSOT functional imaging results reveals that after the injection of OPN Ab‐Au/FeNiPO 4 @ICG nanoprobe, the carotid plaque exhibited a much higher MSOT signal than the aortic arch plaque ( P = 0.0291). Further pathological analysis displays that the carotid plaque possessed a much higher vulnerability score ( P = 0.0247), in agreement with the MSOT signals. More importantly, the linear regression analysis confirms the high correlation between the MSOT signals and plaque vulnerability with R = 0.7095 ( P = 0.0216), demonstrating the potential of the proposed nanoprobe in systematic evaluation of plaque vulnerability. This work employs the dual‐model nanoprobe strategy for both plaque localization and vulnerability assessment, greatly advancing the accurate diagnosis of ASCVD.

Au/FeNiPO<sub>4</sub>‐Based Multiple Spectra Optoacoustic Tomography/CT Dual‐Mode Nanoprobe for Systemic Screening of Atherosclerotic Vulnerable Plaque

Au/FeNiPO4‐Based Multiple Spectra Optoacoustic Tomography/CT Dual‐Mode Nanoprobe for Systemic Screening of Atherosclerotic Vulnerable Plaque