title: Mechanisms for Induction of Pulmonary Capillary Hemorrhage by Diagnostic Ultrasound: Review and Consideration of Acoustical Radiation Surface Pressure.
abstract: Diagnostic ultrasound can induce pulmonary capillary hemorrhage (PCH) in rats and other mammals. This phenomenon represents the only clearly demonstrated biological effect of (non-contrast enhanced) diagnostic ultrasound and thus presents a uniquely important safety issue. However, the physical mechanism responsible for PCH remains uncertain more than 25 y after its discovery. Experimental research has indicated that neither heating nor acoustic cavitation, the predominant mechanisms for bioeffects of ultrasound, is responsible for PCH. Furthermore, proposed theoretical mechanisms based on gas-body activation, on alveolar resonance and on impulsive generation of liquid droplets all appear unlikely to be responsible for PCH, owing to unrealistic model assumptions. Here, a simple model based on the acoustical radiation surface pressure (ARSP) at a tissue-air interface is hypothesized as the mechanism for PCH. The ARSP model seems to explain some features of PCH, including the approximate frequency independence of PCH thresholds and the dependence of thresholds on biological factors. However, ARSP evaluated for experimental threshold conditions appear to be too weak to fully account for stress failure of pulmonary capillaries, gauging by known stresses for injurious physiologic conditions. Furthermore, consideration of bulk properties of lung tissue suggests substantial transmission of ultrasound through the pleura, with reduced ARSP and potential involvement of additional mechanisms within the pulmonary interior. Although these recent findings advance our knowledge, only a full understanding of PCH mechanisms will allow development of science-based safety assurance for pulmonary ultrasound.
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: douglm@umich.edu.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Miller
mesh_terms: D000162:Acoustics; D000818:Animals; D002196:Capillaries / Q000000981:diagnostic imaging* / Q000503:physiopathology; D004195:Disease Models, Animal; D006470:Hemorrhage / Q000000981:diagnostic imaging* / Q000503:physiopathology; D008168:Lung / Q000098:blood supply* / Q000000981:diagnostic imaging; D008171:Lung Diseases / Q000000981:diagnostic imaging* / Q000503:physiopathology; D051379:Mice; D011312:Pressure; D011817:Rabbits; D051381:Rats; D014463:Ultrasonography / Q000379:methods*
keywords: Lung injury mechanisms; Mechanical index; Non-ionizing radiation biology; Point-of-care ultrasound; Pulmonary ultrasound