Most reported photoacoustic ocular imaging work to date uses small animals, such as mice and rats, the eyeball sizes of which are less than one-third of those of humans, posing challenges for clinical translation. Here we developed a novel integrated photoacoustic microscopy (PAM) and optical coherence tomography (OCT) system for dual-modality chorioretinal imaging of larger animals, such as rabbits. The system has quantified lateral resolutions of 4.1 µm (PAM) and 3.8 µm (OCT), and axial resolutions of 37.0 µm (PAM) and 4.0 µm (OCT) at the focal plane of the objective. Experimental results in living rabbits demonstrate that the PAM can noninvasively visualize individual depth-resolved retinal and choroidal vessels using a laser exposure dose of ~80 nJ below the American National Standards Institute (ANSI) safety limit 160 nJ at 570 nm; and the OCT can finely distinguish different retinal layers, the choroid, and the sclera. This reported work may be a major step forward in clinical translation of the technology.

We investigate the production of electron beams from the interaction of relativistically-intense laser pulses with a solid-density SiO(2) target in a regime where the laser pulse energy is approximately mJ and the repetition rate approximately kHz. The electron beam spatial distribution and spectrum were investigated as a function of the plasma scale length, which was varied by deliberately introducing a moderate-intensity prepulse. At the optimum scale length of lambda/2, the electrons are emitted in a collimated beam having a quasimonoenergetic distribution that peaked at approximately 0.8 MeV. A highly reproducible structure in the spatial distribution exhibits an evacuation of electrons along the laser specular direction and suggests that the electron beam duration is comparable to that of the laser pulse. Particle-in-cell simulations which are in good agreement with the experimental results offer insights on the acceleration mechanism by the laser field.

Antivascular therapy represents a proven strategy to treat angiogenesis. By applying synchronized ultrasound bursts and nanosecond laser irradiation, we developed a novel, selective, non-invasive, localized antivascular method, termed photo-mediated ultrasound therapy (PUT). PUT takes advantage of the high native optical contrast among biological tissues and can treat microvessels without causing collateral damage to the surrounding tissue. In a chicken yolk sac membrane model, under the same ultrasound parameters (1 MHz at 0.45 MPa and 10 Hz with 10% duty cycle), PUT with 4 mJ/cm2 and 6 mJ/cm2 laser fluence induced 51% (p = 0.001) and 37% (p = 0.018) vessel diameter reductions respectively. With 8 mJ/cm2 laser fluence, PUT would yield vessel disruption (90%, p < 0.01). Selectivity of PUT was demonstrated by utilizing laser wavelengths at 578 nm or 650 nm, where PUT selectively shrank veins or occluded arteries. In a rabbit ear model, PUT induced a 68.5% reduction in blood perfusion after 7 days (p < 0.001) without damaging the surrounding cells. In vitro experiments in human blood suggested that cavitation may play a role in PUT. In conclusion, PUT holds significant promise as a novel non-invasive antivascular method with the capability to precisely target blood vessels.