In vivo spatiotemporal characterizing diverse body transportation of optical labeled high immunity aluminium adjuvants with photoacoustic tomography.

Vaccine development requires high-resolution, in situ, and visual adjuvant technology. To address this need, this work proposed a novel adjuvant labeling that involved indocyanine green (ICG) and bovine serum albumin (BSA) with self-assembled aluminium adjuvant (Alum), which was called BSA@ICG@Alum. This compound exhibited excellent photoacoustic properties and has been confirmed its safety, biocompatibility, high antigen binding efficiency, and superior induction of immune response. Photoacoustic tomography (PAT) tracked the distribution of Alum in lymph nodes (LNs) and lymphatic vessels in real time after diverse injection modalities. The non-invasive imaging approach revealed that BSA@ICG@Alum was transported to the draining LNs 60 min after intramuscular injection and to distal LNs within 30 min after lymph node injection. In conclusion, PAT enabled real-time three-dimensional and quantitative visualization, thus offering a powerful tool for advancing vaccine design by providing critical insights into adjuvant transport and immune system activation.

Dynamic characterization of vascular response and treatment in oral traumatic ulcer in mice via photoacoustic imaging.

Background: Dynamic surveillance of vasculature is essential for evaluating the healing of oral ulcer. Existing techniques used in vascular imaging face limitations, such as inadequate spatial resolution, restricted diagnostic depth, and the necessity of exogenous contrast agents. Therefore, this study aimed to use robust photoacoustic imaging (PAI) for the dynamic monitoring of vascular response during healing and the associated treatment process of oral ulcer. Methods: Kunming mice (male, 8 weeks old, 31-41 g) were treated with 50% acetic acid for 90 s on the tongue mucosa for induction of oral traumatic ulcer. Mice were randomly divided into three groups (n=12): the control, compound chamomile and lidocaine hydrochloride gel (CCLH), and phycocyanin (PC) groups. PAI was then conducted on days 0, 2, 3, 5, and 7 to obtain vessel parameters of the ulcer area, including vessel intensity, density, mean diameter, maximum diameter, and curvature. Immunohistochemical and hematoxylin and eosin (HE) staining were performed on days 3 and 7 to assess microvessel density and inflammation score. The ulcer healing rate and body weight changes were evaluated for clinical observation. Results: Beginning on the second day after ulcer induction, there was a progressive increase over time in blood intensity and vessel parameters, including vascular density and diameter. On day 7, the CCLH and PC groups demonstrated significantly higher measures than did the control group in terms of blood intensity (P<0.05 and P<0.01), vascular density (both P values <0.05), mean diameter (both P values <0.01), and maximum diameter (P<0.01 and P<0.05). Vessel curvature in the two treatment groups exhibited no significant differences compared to that in the control group (both P values >0.05). The effects of vascular morphological changes were further supported by the histological and clinical outcomes. On day 7, compared to that of the control group, the level of microvessel density was significantly higher in both the CCLH (P<0.01) and PC (P<0.05) groups. The histopathological score in PC group was significantly lower than that of the control group on day 7 (P<0.05). Additionally, compared to that of the control group, the healing rates of the CCLH (P<0.01) and PC groups (P<0.05) were superior on day 7. On day 3, the control group showed more weight loss than did the CCLH (P<0.05) and PC (P<0.01) groups. Conclusions: These findings indicate that PAI is a valuable strategy for the dynamic and quantitative analysis of vascular alterations in oral traumatic ulcers and support its prospective application in improving clinical treatment.

In vivo quantitative characterization of nano adjuvant transport in the tracheal layer by photoacoustic imaging.

Adjuvants are indispensable ingredients in vaccine formulations. Evaluating the in vivo transport processes of adjuvants, particularly for inhalation formulations, presents substantial challenges. In this study, a nanosized adjuvant aluminum hydroxide (AlOOH) was synthesized and labeled with indocyanine green (ICG) and bovine serum albumin (BSA) to achieve strong optical absorption ability and high biocompatibility. The adjuvant nanomaterials (BSA@ICG@AlOOH, BIA) were delivered as an aerosol into the airways of mice, its distribution was monitored using photoacoustic imaging (PAI) in vivo. PAI results illustrated the gradual cross-layer transmission process of BIA in the tracheal layer, traversing approximately 250 µm from the inner layer of the trachea to the outer layer. The results were consistent with pathology. While the intensity of the BIA reduced by approximately 46.8% throughout the transport process. The ability of PAI for quantitatively characterized the dynamic transport process of adjuvant within the tracheal layer may be widely used in new vaccine development.

Subcutaneous injection of hyaluronic acid leading to emboliom and recanalization process monitored in real time by three-dimensional photoacoustic imaging.

This study describes a method for real-time examination of the microvascular system based on the three-dimensional photoacoustic imaging system to prevent arterial complications, especially vascular embolism, during hyaluronic acid (HA) injections. Chicken embryos were used to simulate the superficial blood vessels of human skin, and then the target area was imaged by the photoacoustic imaging system for three-dimensional vascular imaging, and then the syringe and blood vessels were monitored, and the syringe angle and penetration depth were adjusted in time using an injection device to avoid puncturing the arterial vasculature and clogging the blood vessels. HA was then injected into smaller vessels on the dorsum of the tongue in mice and into thicker vessels on the dorsal portion of the tongue in rats to mimic embolization, and the post-operative recovery was reflected by the changes in the pixel dots of the extracted part of the blocked blood vessels, and it was observed that the blood flow in the area of the fine vessels was restored in about 3 days, whereas blood flow in the area of the large vessels was restored in only about 1 h. The method presented in this paper allows precise guidance of injectable filler HA, which has good application prospects in improving the safety of injection micro-plastic surgery and reducing the experience requirements for medical personnel.

High Contrast Detection of Carotid Neothrombus with Strong Near-Infrared Absorption Selenium Nanosphere Enhanced Photoacoustic Imaging.

Background: Carotid artery thrombosis is the leading cause of stroke. Since there are no apparent symptoms in the early stages of carotid atherosclerosis onset, it causes a more significant clinical diagnosis. Photoacoustic (PA) imaging provides high contrast and good depth information, which has been used for the early detection and diagnosis of many diseases. Methods: We investigated thrombus formation by using 20% ferric chloride (FeCl3) in the carotid arteries of KM mice for the thrombosis model. The near-infrared selenium/polypyrrole (Se@PPy) nanomaterials are easy to synthesize and have excellent optical absorption in vivo, which can be used as PA contrast agents to obtain thrombosis information. Results: In vitro experiments showed that Se@PPy nanocomposites have fulfilling PA ability in the 700 nm to 900 nm wavelength range. In the carotid atherosclerosis model, maximum PA signal enhancement up to 3.44, 4.04, and 5.07 times was observed by injection of Se@PPy nanomaterials, which helped to diagnose the severity of carotid atherosclerosis. Conclusion: The superior PA signal of Se@PPy nanomaterials can identify the extent of atherosclerotic carotid lesions, demonstrating the feasibility of PA imaging technology in diagnosing carotid thrombosis lesion formation. This study demonstrates nanocomposites and PA techniques for imaging and diagnosing carotid thrombosis in vivo.

Visualizing the early-stage testicular torsion by dual-modal photoacoustic and ultrasound imaging.

Delayed treatment of testicular torsion (TT) can lead to permanent loss of reproductive capacity. Photoacoustic imaging (PAI) and ultrasound imaging (USI) was tested for detecting TT at early stage in mice based on PAI-obtained oxygen saturation (sO2), and USI-collected color pixel density (CPD), peak systolic velocity (PSV) and resistance index (RI). For complete TT, both CPD (9.08 % ± 3.084 to almost zero) and sO2 data (70.09 % ± 1.656-59.84 % ± 1.427) showed an significant change 2 h post-torsion. For incomplete TT, sO2 data exhibited a strong time relationship (Mean values: 6 h, 64.83 % ± 1.898; 12 h, 60.67 % ± 3.555; 24 h, 57.85 % ± 3.575; P < 0.05). However, USI-collected CPD, PSV or IR data from the same TT models showed no significant difference. This study indicated that USI and PAI could identify complete TT. Meanwhile, PAI has shown great potential in the diagnosis of incomplete TT within 24 h based on time-related sO2 map.