Label-free photoacoustic and ultrasound imaging for murine atherosclerosis characterization

Dual-modality photoacoustic tomography (PAT) and 4D ultrasound (4DUS) imaging have shown promise for cardiovascular applications, but their use in murine atherosclerosis imaging is limited. This study used PAT and 4DUS to correlate altered arterial strain and hemodynamics to morphological changes and lipid localization in a murine partial carotid ligation (PCL) model of atherosclerosis. Validation experiments showed a positive correlation between the PAT signal-to-noise ratio and plaque lipid composition obtained from oil-red O histology. Cross-sectional in situ PAT and longitudinal in vivo ultrasound imaging was performed using a 40MHz transducer. Ultrasound timepoints included days 0, 1, 4, 7, 10, and 14 for hemodynamic and strain assessment, and 1100nm and 1210nm PAT was implemented at the study end point for hemoglobin and lipid characterization. These study groups were then separated into day 4 post-PCL with (n¼5) and without (n¼6) Western diet feeding, as well as days 7 (n¼ 8), 10 (n¼ 8), and 14 (n¼8) post-PCL, in addition to a sham control group on a Western diet (n¼ 5). Overall, our data revealed a substantial decrease in left carotid artery pulsatility by day 7. The hemo- dynamic results suggested greater disturbed flow in the caudal regions resulting in earlier vessel stenosis and greater lipid deposition than cranial regions. Morphological and compositional data revealed heterogeneous vascular remodeling between days 0 and 7, with a rapid decrease in the vessel volume/length and the presence of both intraplaque hematoma and lipid deposition at day 10 post-PCL. These results highlight the utility of utilizing dual-modality PAT and 4DUS to study atherosclerosis progression.