title: Disruption of tumor neovasculature by microbubble enhanced ultrasound: a potential new physical therapy of anti-angiogenesis.
abstract: Tumor angiogenesis is of vital importance to the growth and metastasis of solid tumors. The angiogenesis is featured with a defective, leaky and fragile vascular construction. Microbubble enhanced ultrasound (MEUS) cavitation is capable of mechanical disruption of small blood vessels depending on effective acoustic pressure amplitude. We hypothesized that acoustic cavitation combining high-pressure amplitude pulsed ultrasound (US) and circulating microbubble could potentially disrupt tumor vasculature. A high-pressure amplitude, pulsed ultrasound device was developed to induce inertial cavitation of circulating microbubbles. The tumor vasculature of rat Walker 256 was insonated percutaneously with two acoustic pressures, 2.6 MPa and 4.8 MPa, both with intravenous injection of a lipid microbubble. The controls were treated by the ultrasound only or sham ultrasound exposure. Contrast enhanced ultrasound (CEUS) and histology were performed to assess tumor circulation and pathological changes. The CEUS results showed that the circulation of Walker 256 tumors could be completely blocked off for 24 hours in 4.8 MPa treated tumors. The CEUS gray scale value (GSV) indicated that there was significant GSV drop-off in both of the two experimental groups but none in the controls. Histology showed that the tumor microvasculature was disrupted into diffuse hematomas accompanied by thrombosis, intercellular edema and multiple cysts formation. The 24 hours of tumor circulation blockage resulted in massive necrosis of the tumor. MEUS provides a new, simple physical method for anti-angiogenic therapy and may have great potential for clinical applications.
authors.affiliation: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, China. liuzhengs@hotmail.com
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Shunji
authors.initials: S
authors.lastname: Gao
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Peijing
authors.initials: P
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Kaibin
authors.initials: K
authors.lastname: Tan
authors.forename: Feng
authors.initials: F
authors.lastname: Xie
mesh_terms: D000818:Animals; D005240:Feasibility Studies; D008297:Male; D045423:Microbubbles / Q000627:therapeutic use*; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014464:Ultrasonic Therapy / Q000379:methods*