Haworth Kevin J, Raymond Jason L, Radhakrishnan Kirthi, Moody Melanie R, Huang Shao-Ling, Peng Tao, Shekhar Himanshu, Klegerman Melvin E, Kim Hyunggun, McPherson David D, Holland Christy K
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.
Biomedical Engineering Program, University of Cincinnati, Cincinnati, Ohio, USA.
Ultrasound Med Biol. 2016 Feb;42(2):518-27. doi: 10.1016/j.ultrasmedbio.2015.08.014. Epub 2015 Nov 4.
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.
对狭窄动脉进行血管成形术和支架植入可使血流急性恢复。然而,根据支架类型,随后可能会发生再狭窄或内皮再生长不足的情况。空化介导的药物递送是针对这些病症的一种潜在疗法,但需要通过超声照射诱导特定类型的空化。由于组织的异质性和空化的随机性,需要反馈机制来确定是否诱导了持续的气泡活动。本研究的目的是确定在流动模型和动物模型中通过金属支架进行被动空化成像的可行性。在本研究中,将血管内支架部署在流动模型和猪股动脉中。将荧光团标记的超声造影剂——回声增强脂质体注射到支架近端。通过被动记录并用低频(500 kHz)换能器照射回声增强脂质体产生的声发射并进行波束形成来获得空化图像。体外实验表明,通过支架检测稳定空化活动的信噪比大于8 dB。支架并未显著降低信噪比。当用500-kHz换能器照射回声增强脂质体时,还通过被动空化成像在体内检测到跨支架空化活动。当检测到稳定空化时,观察到荧光团向动脉壁内的递送。给予回声增强脂质体时,还观察到支架内回声增强。因此,在体内存在血管内支架的情况下,B型超声成像和空化成像都是可行的。这种能力的证明支持了未来利用超声造影监测再狭窄以及进行图像引导的超声介导药物递送以抑制再狭窄的研究。