title: Trans-Stent B-Mode Ultrasound and Passive Cavitation Imaging.
abstract: Angioplasty and stenting of a stenosed artery enable acute restoration of blood flow. However, restenosis or a lack of re-endothelization can subsequently occur depending on the stent type. Cavitation-mediated drug delivery is a potential therapy for these conditions, but requires that particular types of cavitation be induced by ultrasound insonation. Because of the heterogeneity of tissue and stochastic nature of cavitation, feedback mechanisms are needed to determine whether the sustained bubble activity is induced. The objective of this study was to determine the feasibility of passive cavitation imaging through a metal stent in a flow phantom and an animal model. In this study, an endovascular stent was deployed in a flow phantom and in porcine femoral arteries. Fluorophore-labeled echogenic liposomes, a theragnostic ultrasound contrast agent, were injected proximal to the stent. Cavitation images were obtained by passively recording and beamforming the acoustic emissions from echogenic liposomes insonified with a low-frequency (500 kHz) transducer. In vitro experiments revealed that the signal-to-noise ratio for detecting stable cavitation activity through the stent was greater than 8 dB. The stent did not significantly reduce the signal-to-noise ratio. Trans-stent cavitation activity was also detected in vivo via passive cavitation imaging when echogenic liposomes were insonified by the 500-kHz transducer. When stable cavitation was detected, delivery of the fluorophore into the arterial wall was observed. Increased echogenicity within the stent was also observed when echogenic liposomes were administered. Thus, both B-mode ultrasound imaging and cavitation imaging are feasible in the presence of an endovascular stent in vivo. Demonstration of this capability supports future studies to monitor restenosis with contrast-enhanced ultrasound and pursue image-guided ultrasound-mediated drug delivery to inhibit restenosis.
authors.affiliation: Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA; Biomedical Engineering Program, University of Cincinnati, Cincinnati, Ohio, USA. Electronic address: kevin.haworth@uc.edu.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Haworth
authors.affiliation: Biomedical Engineering Program, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Raymond
authors.affiliation: Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Kirthi
authors.initials: K
authors.lastname: Radhakrishnan
authors.affiliation: Division of Cardiology, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Melanie R
authors.initials: MR
authors.lastname: Moody
authors.affiliation: Division of Cardiology, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Shao-Ling
authors.initials: SL
authors.lastname: Huang
authors.affiliation: Division of Cardiology, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
authors.affiliation: Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Shekhar
authors.affiliation: Division of Cardiology, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Melvin E
authors.initials: ME
authors.lastname: Klegerman
authors.affiliation: Division of Cardiology, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Hyunggun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: David D
authors.initials: DD
authors.lastname: McPherson
authors.affiliation: Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA; Biomedical Engineering Program, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Christy K
authors.initials: CK
authors.lastname: Holland
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000032:analysis / Q000737:chemistry / Q000528:radiation effects; D005263:Femoral Artery / Q000000981:diagnostic imaging* / Q000528:radiation effects / Q000601:surgery*; D005466:Fluorocarbons / Q000737:chemistry* / Q000528:radiation effects; D005740:Gases / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry; D019220:High-Energy Shock Waves; D013010:Sonication / Q000379:methods*; D015607:Stents; D013552:Swine; D013556:Swine, Miniature; D014463:Ultrasonography / Q000379:methods*
chemical_list: D003287:Contrast Media; D005466:Fluorocarbons; D005740:Gases; C042852:perflutren
keywords: Cavitation imaging; Drug delivery; Endovascular stent; Image-guided therapy; Passive acoustic mapping; Targeted liposomes; Ultrasound contrast agent