Investigations into pulsed high-intensity focused ultrasound-enhanced delivery: preliminary evidence for a novel mechanism.

Investigations into pulsed high-intensity focused ultrasound-enhanced delivery: preliminary evidence for a novel mechanism.
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DOI:
10.1016/j.ultrasmedbio.2009.04.020
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发表时间:
2009-10
影响因子:
2.9
通讯作者:
Frenkel, Victor
Frenkel, Victor
中科院分区:
医学3区
文献类型:
--
作者:
Hancock, Hilary A.;Smith, Lauren H.;Cuesta, Julian;Durrani, Amir K.;Angstadt, Mary;Palmeri, Mark L.;Kimmel, Eitan;Frenkel, Victor

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不使用超声造影剂的脉冲高强度聚焦超声(HIFU)暴露已被用于非侵入性地增强各种药剂的递送,从而以非破坏性的方式提高其在各种组织模型中的治疗效果。尽管这些暴露具有多种用途,但对其产生影响的机制却知之甚少。在这项研究中,对小鼠的胁腹肌进行脉冲 HIFU 照射,然后通过局部或全身注射施用各种荧光团,包括可溶性荧光团和颗粒荧光团。体内成像(整个动物和显微镜)用于量化由于暴露而增加的荧光团外渗和间质运输的观察结果。组织学分析表明,暴露引起了一些结构改变,例如肌纤维之间的间隙增大。这些效应与增加组织的渗透性是一致的。然而,它们被发现是暂时的,并在 72 小时内逐渐逆转。对辐射力引起的位移及其产生的局部剪切应变进行了模拟,以潜在地解释这些效应发生的方式。更好地了解脉冲 HIFU 照射用于非侵入性增强递送的机制将有助于优化其使用过程。
Pulsed-high intensity focused ultrasound (HIFU) exposures without ultrasound contrast agents have been used for non-invasively enhancing the delivery of various agents to improve their therapeutic efficacy in a variety of tissue models in a non-destructive manner. Despite the versatility of these exposures, little is known about the mechanisms by which their effects are produced. In this study pulsed-HIFU exposures were given in the flank muscle of mice, followed by the administration a variety of fluorophores, both soluble and particulate, by local or systemic injection. In vivo imaging (whole animal and microscopic) was used to quantify observations of increased extravasation and interstitial transport of the fluorophores as a result of the exposures. Histological analysis indicated that the exposures caused some structural alterations such as enlarged gaps between muscle fibers. These effects were consistent with increasing the permeability of the tissues; however they were found to be transient and reversed themselves gradually within 72 hrs. Simulations of radiation force induced displacements and the resulting local shear strain they produced were carried out to potentially explain the manner by which these effects occurred. A better understanding of the mechanisms involved with pulsed-HIFU exposures for non-invasively enhancing delivery will facilitate the process for optimizing their use.
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