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Yannis Mantas Paulus, Zizhong Hu, Xinmai Yang, Aghapi Mordovanakis, Xueding Wang; Photo-mediated ultrasound therapy as a novel method to selectively treat small blood vessels. Invest. Ophthalmol. Vis. Sci. 2016;57(12):No Pagination Specified.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal and choroidal neovascularization and vascularization play a pivotal role in the leading causes of blindness including macular degeneration and diabetic retinopathy, but conventional laser treatment results in thermal damage to surrounding tissue. Using low intensity laser concurrently with relatively low intensity ultrasound, we developed a novel treatment: photo-mediated ultrasound therapy (PUT). We studied PUT in 300 chicken embryos to determine parameters leading to small blood vessel shrinkage, ablation, and rupture without damaging surrounding tissue.
An integrated high intensity focused ultrasound (HIFU, H102 Sonic Concepts) and laser treatment system was devised. A Nd:YAG laser pumped a tunable optical parametric oscillator (Surelite OPO PLUS, Continuum) which emits 5-ns, 10 Hz pulses. On embryo development day (EDD) 3, fertilized chicken eggs were removed from the 38°C incubator, cracked, and transferred to sterile petri dishes until treatment, when they were exposed to laser + ultrasound, ultrasound-only, or laser-only at wavelengths of 532, 578, or 650 nm. Ultrasound bursts with 10% duty cycle at 1 MHz were applied concurrently with laser pulses. The change in the vessel diameter was evaluated using independent T test and the incidence of vascular rupture or thrombus was evaluated using Fisher’s exact T test.
At 532 nm laser and 1.1 MPa ultrasound, 4 mJ/cm2 laser fluence induced vein size reduction from 206.21 ± 44.60 to 99.81 ± 44.49 µm (Figure 1A-C, p<0.01). Six mJ/cm2 and 8 mJ/cm2 induced vein rupture in the majority of cases (Figure 1D, p<0.001). No effect was noted for laser or ultrasound alone. For 578 nm laser, a dose response-induced vein shrinkage was induced. At 650 nm laser, the PUT system with laser power from 6 to 18 mJ/cm2 selectively affected arteries over veins.
In chicken embryos, 532 nm laser light can mediate ultrasound pulses to induce blood vessel shrinkage. Selectivity of treating veins and arteries can be achieved with adjusting the wavelength, with 578 nm laser selectively inducing venous shrinkage and 650 nm inducing arterial shrinkage and thrombus in chicken embryos where the veins are oxygenated. PUT may have a role in treating blood vessels without damaging surrounding tissue.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
A. Vein before treatment. B. After 532nm laser 4mJ/cm2 + HIFU. C. Laser+HIFU effect on vein size. D. Laser+HIFU effect on vessel rupture
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