title: 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/cm2and 6 mJ/cm2laser fluence induced 51% (p = 0.001) and 37% (p = 0.018) vessel diameter reductions respectively. With 8 mJ/cm2laser 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.
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.|Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA.|Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Zizhong
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, MI, USA.|Institute of Acoustics, Tongji University, Shanghai, P.R. China.
authors.forename: Haonan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Aghapi
authors.initials: A
authors.lastname: Mordovanakis
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.|Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Yannis M
authors.initials: YM
authors.lastname: Paulus
authors.affiliation: Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Qinghuai
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.|Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Xueding
authors.initials: X
authors.lastname: Wang
authors.affiliation: Bioengineering Research Center and Department of Mechanical Engineering, University of Kansas, Lawrence, KS, USA.
authors.forename: Xinmai
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D001769:Blood / Q000528:radiation effects; D002645:Chickens; D004423:Ear / Q000098:blood supply / Q000528:radiation effects; D006801:Humans; D028022:Low-Level Light Therapy; D009389:Neovascularization, Pathologic / Q000532:radiotherapy*; D011817:Rabbits; D014464:Ultrasonic Therapy; D015017:Yolk Sac / Q000098:blood supply / Q000528:radiation effects