Colloidal gold nanoparticles (GNPs) serve as promising contrast agents in photoacoustic (PA) imaging, yet their utility is limited due to their absorption peak in the visible window overlapping with that of hemoglobin. To overcome such limitation, this report describes an ultrapure chain-like gold nanoparticle (CGNP) clusters with a redshift peak wavelength at 650 nm. The synthesized CGNP show an excellent biocompatibility and photostability. These nanoparticles are conjugated with arginine-glycine-aspartic acid (RGD) peptides (CGNP clusters-RGD) and validated in 12 living rabbits to perform multimodal photoacoustic microscopy (PAM) and optical coherence tomography (OCT) for visualization of newly developed blood vessels in the sub-retinal pigment epithelium (RPE) space of the retina, named choroidal neovascularization (CNV). The PAM system can achieve a 3D PAM image via a raster scan of 256 × 256 pixels within a time duration of 65 s. Intravenous injection of CGNP clusters-RGD bound to CNV and resulted in up to a 17-fold increase in PAM signal and 176% increase in OCT signal. Histology indicates that CGNP clusters could disassemble, which may facilitate its clearance from the body.

Photoacoustic microscopy (PAM) is an emerging imaging technology that can non-invasively visualize ocular structures in animal eyes. This report describes an integrated multimodality imaging system that combines PAM, optical coherence tomography (OCT), and fluorescence microscopy (FM) to evaluate angiogenesis in larger animal eyes. High-resolution in vivo imaging was performed in live rabbit eyes with vascular endothelial growth factor (VEGF)-induced retinal neovascularization (RNV). The results demonstrate that our multimodality imaging system can non-invasively visualize RNV in both albino and pigmented rabbits to determine retinal pathology using PAM and OCT and verify the leakage of neovascularization using FM and fluorescein dye. This work presents high-resolution visualization of angiogenesis in rabbits using a multimodality PAM, OCT, and FM system and may represent a major step toward the clinical translation of the technology.

Joint high-resolution multimodal photoacoustic microscopy (PAM) and optical coherence tomography (OCT) was developed to improve the efficiency for visualizing newly developed retinal neovascularization (RNV) and to monitor the dynamic changes of retinal vein occlusion (RVO) in living rabbits. The RNV and RVO models were created in New Zealand rabbits by Rose Bengal laser-induced RVO. Dual modalities imaging equipment, including color fundus photography, fluorescein angiography (FA), OCT, and PAM, was used to image and assess the changes of retinal vasculature. In vivo experimental results exhibited that not only the treatment boundaries and the position of the occluded vasculature but also the structure of individual RNV were markedly observed using PAM platform with great resolution and high image contrast. The laser light energy of 80 nJ was used to induce photoacoustic signal, which is approximately half the energy of the American National Standards Institute safety limit. A cross-sectional structure of RNV was identified with the OCT modality. Furthermore, vibrant transformations in the RNV and the retinal morphology were examined at different times after laser occlusion: days 4, 28, 35, 49, and 90. PAM revealed high contrast and high resolution vascular imaging of the retina and choroid with amplified penetration depth. Through the present custom-built imaging system, both RNV and RVO can be reconstructed and observed in two and three dimensions. A unique dual modality A unique dual modality PAM and OCT can help precisely visualize and distinguish individual microvessels, microvessel depth, and the surrounding anatomy. Thus, the proposed multimodal ocular imaging platform may offer a potential equipment to enhance classification of microvasculature in a reliable and proficient manner in larger rabbit eyes.

No abstract

In myopia, diabetes and aging, fibrous vitreous liquefaction and degeneration is associated with the formation of opacities within the vitreous body that cast shadows on the retina, appearing as 'floaters' to the patient. Vitreous opacities degrade contrast sensitivity function and can cause significant impairment in vision-related quality-of-life. This study introduces 'nanobubble ablation' for safe destruction of vitreous opacities. Following intravitreal injection, hyaluronic acid coated gold nanoparticles and indocyanine green, which is widely used as a dye in vitreoretinal surgery, spontaneously accumulate on collagenous vitreous opacities in the eyes of rabbits. Applying nanosecond laser pulses generates vapor nanobubbles which mechanically destroy the opacities in rabbit eyes and in patients specimens. Nanobubble ablation might offer a safe and efficient treatment to millions of patients suffering from debilitating vitreous opacities and paves the way for a highly safe use of pulsed lasers in the posterior segment of the eye.

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.

Although photoacoustic microscopy (PAM) and optical coherence tomography (OCT) allow visualization of the retinal microvasculature, distinguishing early neovascularization from adjacent vessels remains challenging. Herein, gold nanostars (GNSs) functionalized with an RGD peptide were utilized as multimodality contrast agents for both PAM and OCT. GNSs have great absorption and scattering characteristics in the near-infrared region where most vasculature and tissue generates a less intrinsic photoacoustic signal while having a small size, excellent biocompatibility in vivo, and great photostability under nanosecond pulsed laser illumination. This enabled visualization and differentiation of individual microvasculature in vivo using multimodal PAM and OCT imaging. Detailed three-dimensional imaging of GNSs was achieved in an important choroidal neovascularization model in living rabbits. Through the administration of GNSs, PA contrast increased up to 17-fold and OCT intensities increased 167%. This advanced molecular-imaging platform with GNSs provides a unique tool for detailed mapping of the pathogenesis of the microvasculature.

Ocular drug delivery remains a grand challenge due to the complex structure of the eye. Here, we introduce a unique platform of ocular drug delivery through the integration of silicon nanoneedles with a tear-soluble contact lens. The silicon nanoneedles can penetrate into the cornea in a minimally invasive manner and then undergo gradual degradation over the course of months, enabling painless and long-term sustained delivery of ocular drugs. The tear-soluble contact lens can fit a variety of corneal sizes and then quickly dissolve in tear fluid within a minute, enabling an initial burst release of anti-inflammatory drugs. We demonstrated the utility of this platform in effectively treating a chronic ocular disease, such as corneal neovascularization, in a rabbit model without showing a notable side effect over current standard therapies. This platform could also be useful in treating other chronic ocular diseases.