Carotid arteries are important channels delivering blood and oxygen to brain. Atherosclerosis plaque in carotid arteries hinders blood delivery, and plaque rupture causes stroke, leading to high morbidity and motility. Extensive preclinical and clinical studies showed that atherosclerosis inflammation activities are highly related to plaque vulnerability. Thus, visualizing the inflammation of atherosclerosis plaques is important in atherosclerosis vulnerability assessment. In this study, photoacoustic imaging modality was applied for carotid atherosclerosis inflammation identification of mouse in vivo. Deficient apolipoprotein E (ApoE-/-) mice with high-fat diet and normal diet for 16 weeks were employed as atherosclerosis models and control models, respectively. Photoacoustic molecular probes with optical absorption at nearinfrared wavelength and specifically target cluster of differentiation 36 (CD36) were employed to mark inflammation cells in carotid atherosclerosis plaques of mouse in vivo. Noninvasive imaging of atherosclerosis inflammation cells marked by molecular probes was performed by point-to-point scanning with a custom-built acoustic-resolution photoacoustic imaging system. Considering low scattering of near-infrared light in tissues and mature commercialization of laser, excitation wavelength in this research is chosen at 1064 nm. Carotid arteries with and without atherosclerosis plaques have been noninvasively imaged and distinguished. Furthermore, carotid atherosclerosis with different inflammation severity has been analyzed by photoacoustic imaging and immunohistochemistry staining. Photoacoustic signal from atherosclerosis arteries showed high relativity with inflammation severity defined by immunohistochemistry staining, evidencing the reliability of the novel imaging technology in atherosclerosis inflammation identification. This study paves the way for photoacoustic imaging technology to atherosclerosis inflammation identification, severity quantification and even further atherosclerosis therapy.
Intravascular photoacoustic imaging (IVPA) can obtain specific inflammation information and lipid composition in vivo, which is a new method for the diagnosis of atherosclerotic plaques. Numerous IVPA systems have been proposed and pushed towards clinical application. But imaging speed hinders their final clinical translation, considering necessary blood flush or balloon blood blockage operations during the intravascular intervention. In this study, we developed a high-speed IVPA system based on a 1064 nm pulsed laser, with the imaging speed of 60 round/second, about twice speed of the fastest IVPA system. In this system, a 0.9 mm outer diameter catheter was used for simultaneous IVPA and IVUS imaging. A plastic tube with an outer diameter of 1.3 mm was wrapped on the outside of the imaging catheter for protection and blood flushing channels. Firstly, the capability of high-speed imaging was verified by the imaging of a manually moving metal needle. Photoacoustic and ultrasonic images of the needle were obtained. No artifacts were found during the real-time imaging of the needle, which was unavoidable in the low-speed imaging system. Then, an artery excised from abdominal aorta of a New Zealand rabbit was sealed and a certain frequency of flowing water was injected from the one end to simulate the pulsation of blood vessels with a frequency of about 4.5 Hz, which was a typical heart rate of a rabbit. The high-speed IVPA-US imaging of pulsed blood vessels was successfully performed, which proved the feasibility of the system in vivo and even further clinical application.