High-precision, non-invasive anti-microvascular approach via concurrent ultrasound and laser irradiation

Abstract

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.

Removal of choroidal vasculature using concurrently applied ultrasound bursts and nanosecond laser pulses

“…We have demonstrated that PUT, as a newly developed antivascular therapeutic method 11 , can non-invasively eliminate microvessels in the choroid in rabbit eyes with excellent efficacy and safety. In comparison with the standard anti-VEGF therapy for wet AMD, PUT removes microvessels through a different mechanism, which is to directly damage vascular endothelial cells through mechanical forces produced via cavitation 11 .…”

“…In comparison with the standard anti-VEGF therapy for wet AMD, PUT removes microvessels through a different mechanism, which is to directly damage vascular endothelial cells through mechanical forces produced via cavitation 11 . Through a single treatment, PUT can largely stop the perfusion in the target area.…”

“…By combining laser and ultrasound, we have recently developed a non-invasive photo-mediated ultrasound therapy (PUT) technique to shut down microvessels 11–13 . PUT is fundamentally different from any of the existing laser or ultrasound-based antivascular technologies including PDT, photothermal therapy, photothermolysis, and antivascular ultrasound therapy.…”

“…PUT is fundamentally different from any of the existing laser or ultrasound-based antivascular technologies including PDT, photothermal therapy, photothermolysis, and antivascular ultrasound therapy. PUT utilizes cavitation-based method to permanently shut down microvessels, and the cavitation produced by PUT is based on the novel photoacoustic cavitation mechanism 11 . More importantly, PUT utilizes concurrently applied ultrasound bursts and laser pulses, both are safe to biological tissues.…”

“…However, unlike PDT which involves a photosensitizer, PUT is completely non-invasive and agent-free, and can offer high treatment precision. This technique has the potential to non-invasively shut down diseased microvessels to achieve optimal treatment outcome for patients 11 .…”