Thrombosis is a main cause of acute cardiovascular events, and detecting thrombi in small arteries via noninvasive imaging remains challenging. In this study, we employed a novel imaging method, photoacoustic imaging (PAI), to study thrombosis in a mouse model of ferric chloride (FeCl₃)-induced arterial thrombosis and compared the ability of this method to detect thrombosis with that of a conventional imaging method, namely, ultrasound. The mice (n = 20) were divided equally into the following 4 groups: (1) a normal group, and (2) 3 experimental groups, in which the left common carotid artery was treated with 20% FeCl₃ for 1, 3, or 5 min, respectively. After 24 h, PAI detected thrombi of different sizes and generated images, enabling us to assess the changes in structure. The results of this study suggest that PAI is a useful, noninvasive visualization tool for investigating the mechanism underlying thrombosis development and is suitable for imaging arterial thrombosis in mouse carotid arteries.

BackgroundSafe and noninvasive on-demand relief is a crucial and effective treatment for postoperative pain because it considers variable timing and intensity of anesthetics. Ultrasound modulation is a promising technique for this treatment because it allows convenient timed and noninvasive controlled drug release.MethodsWe created an ultrasound-triggered lidocaine (Lido) release platform using an amino acid hydrogel functioning as three dimensional (3D) scaffold material (Lido-PPIX@ER hydrogel). Optimal preparation conditions and ultrasound-triggered parameters were evaluated. In the postoperative pain SD rat model, the Lido-PPIX@ER hydrogel or free lidocaine was administered by subcutaneous injection immediately after making the paw incision. Mechanical hypersensitivity was assessed using calibrated von Frey filaments after an individualized (highly variable) ultrasound-triggered process. The safety of the treatment was also evaluated.ResultsThe Lido-PPIX@ER hydrogel allows control of the timing, intensity and duration of lidocaine (Lido) to relieve postoperative pain. The hydrogel releases Lido due to the elevated reactive oxygen species (ROS) levels generated by PPIX under ultrasound triggering. The optimal ultrasound parameter (0.3 W/cm2, 30 s) was chosen for in vitro and in vivo studies. The Lido-PPIX@ER hydrogel (with lidocaine, 5.6 mg/mL) under individualized ultrasound triggering (every 2 h in the first 12 h, every 4 h for the next 36 h, and then every 6 h until 72 h postsurgery) released lidocaine and provided effective analgesia for more than 72 h. Additionally, the withdrawal threshold was higher than that in the control group at all time points measured. The hydrogel showed repeatable and adjustable ultrasound-triggered nerve blocks in vivo, the duration of which depended on the extent and intensity of insonation. On histopathology, no systemic effect or tissue reaction was observed in the ultrasound-triggered Lido-PPIX@ER hydrogel-treated group.ConclusionsThe Lido-PPIX@ER hydrogel with individualized (highly variable) ultrasound triggering is a convenient and effective method that offers timed and spatiotemporally controlled Lido release to manage postoperative pain.