Abstract
Multimodal imaging with photoacoustic microscopy (PAM) and optical coherence tomography (OCT) can be an effective method to evaluate the choroidal and retinal microvasculature. To improve the efficiency for visualizing capillaries, colloidal gold nanoparticles (AuNPs) have been applied as a multimodal contrast agent for both OCT and PAM imaging by taking advantage of the strong optical scattering and the strong optical absorption of AuNPs due to their surface plasmon resonance. Ultra-pure AuNPs were fabricated by femtosecond laser ablation, capped with polyethylene glycol (PEG), and administered to 13 New Zealand white rabbits and 3 Dutch Belted pigmented rabbits. The synthesized PEG-AuNPs (20.0 ± 1.5 nm) were demonstrated to be excellent contrast agents for PAM and OCT, and do not demonstrate cytotoxicity to bovine retinal endothelial cells in cell studies. The image signal from the retinal and choroidal vessels in living rabbits was enhanced by up to 82% for PAM and up to 45% for OCT, respectively, by the administered PEG-AuNPs, which enables detection of individual blood vessels by both imaging modalities. The biodistribution study demonstrated the AuNP accumulated primarily in the liver and spleen. Histology and TUNEL staining did not indicate cell injury or death in the lung, liver, kidney, spleen, heart, or eyes up to seven days after AuNP administration. PEG-AuNPs offer an efficient and safe contrast agent for multimodal ocular imaging to achieve improved characterization of microvasculature.
Highlights
Www.nature.com/scientificreports with depth information but does not demonstrate leakage, provides limited visualization of microaneurysms, and has a restricted field of view often with artifacts
The current study demonstrates that AuNPs can increase photoacoustic microscopy (PAM) signals of the blood vessels by 52% (2 mg/mL) and 82% (5 mg/mL) in comparison with the control
This result suggests that polyethylene glycol (PEG)-AuNPs could perform as an efficient contrast agent to improve PAM imaging www.nature.com/scientificreports for the evaluation of individual retinal and choroidal microvasculature, which can be important in diseases such as macular degeneration and diabetic retinopathy
Summary
Www.nature.com/scientificreports with depth information but does not demonstrate leakage, provides limited visualization of microaneurysms, and has a restricted field of view often with artifacts. Photoacoustic imaging is a hybrid, non-ionizing, and non-invasive imaging modality with micron-scale spatial resolution and millimeter-scale depth penetration[9,10] It is being explored in visualizing tissue structure and function in biomedical applications, such as imaging of brain, liver, breast, joints, and eye[11,12,13,14]. The level of contrast enhancement by organic agents can be limited Inorganic contrast agents, such as gold particles (AuNPs), have exhibited promising results in photoacoustic molecular imaging[12]. PEG derivatives were used to optimize the surface properties and functionalities, enhance the solubility, stability, and biocompatibility, and prolong the systemic circulation time of AuNPs. This study evaluates the safety and utility of PEG-AuNPs in living rabbits as a multimodal OCT and PAM contrast agent for examination of retinal and choroidal microvasculature
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