Passive cavitation detection during pulsed HIFU exposures of ex vivo tissues and in vivo mouse pancreatic tumors.
Passive cavitation detection during pulsed HIFU exposures of ex vivo tissues and in vivo mouse pancreatic tumors.
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DOI：
10.1016/j.ultrasmedbio.2014.01.007
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发表时间：
2014-07
影响因子：
2.9
通讯作者：
Hwang, Joo Ha
中科院分区：
文献类型：
--
作者：
Li, Tong;Chen, Hong;Khokhlova, Tatiana;Wang, Yak-Nam;Kreider, Wayne;He, Xuemei;Hwang, Joo Ha
关键词：
脉冲高强度聚焦超声（pHIFU）已被证明可以增强血管通透性，破坏肿瘤屏障，并通过声空化促进药物进入肿瘤组织。因此，在pHIFU治疗过程中监测空化活动，了解足以在给定组织中可靠地诱导空化的超声压力水平是非常重要的。本文介绍了用共聚焦被动空化检测方法评价pHIFU诱导空化活性的三个指标：空化概率、空化持久性和宽带声发射水平。这些指标被用来表征几种离体组织类型（牛舌和肝脏以及猪脂肪组织和肾脏）和凝胶幻象（聚丙烯酰胺和琼脂糖）在不同的峰比例焦压力（1 - 12 MPa）下的空化活性，在以下pHIFU方案中：频率1.1 MHz，脉冲持续时间1 ms，脉冲重复频率1 Hz。为了评估这些测量在离体组织中的相关性，我们还研究并比较了在转基因KPC小鼠中自发发展的小鼠胰腺肿瘤的离体和体内空化指标，这些肿瘤在形态上与人类疾病非常相似。空化阈值，定义为50%的空化概率，发现在所研究的组织中差异很大（在2.5-10 MPa范围内），主要取决于表征组织组成的水脂比。空化持久性和宽带发射强度取决于组织结构和脂质浓度。离体和体内胰腺肿瘤组织的空化阈值和宽带噪声发射水平相似。在体内和离体环境中，最大的差异是在整个pHIFU暴露过程中出现空化的模式：在体内是零星的，但在体外迅速减少，并在最初的几个脉冲内停止。空化活性依赖于空化核的破坏与循环的相互作用，空化核不仅在HIFU治疗中被消耗，在体内也会被循环补充或带走。这些发现对于phifu诱导的药物递送的治疗计划和优化具有重要意义，特别是对于胰腺肿瘤。
Pulsed high-intensity focused ultrasound (pHIFU) has been demonstrated to enhance vascular permeability, disrupt tumor barriers and enhance drug penetration into tumor tissue through acoustic cavitation. Monitoring of cavitation activity during pHIFU treatments and knowing the ultrasound pressure levels sufficient to reliably induce cavitation in a given tissue are therefore very important. Here, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitation detection were introduced: cavitation probability, cavitation persistence and the level of the broadband acoustic emissions. These metrics were used to characterize cavitation activity in several ex vivo tissue types (bovine tongue and liver and porcine adipose tissue and kidney) and gel phantoms (polyacrylamide and agarose) at varying peak-rarefactional focal pressures (1–12 MPa) during the following pHIFU protocol: frequency 1.1 MHz, pulse duration 1 ms, pulse repetition frequency 1 Hz. To evaluate the relevance of the measurements in ex vivo tissue, cavitation metrics were also investigated and compared in the ex vivo and in vivo murine pancreatic tumors that develop spontaneously in transgenic KPC mice and closely recapitulate human disease in their morphology. The cavitation threshold, defined at 50 % cavitation probability, was found to vary broadly among the investigated tissues (within 2.5–10 MPa), depending mostly on the water-lipid ratio that characterizes the tissue composition. Cavitation persistence and the intensity of broadband emissions depended both on tissue structure and lipid concentration. Both the cavitation threshold and broadband noise emission level were similar between ex vivo and in vivo pancreatic tumor tissue. The largest difference between in vivo and ex vivo settings was found in the pattern of cavitation occurrence throughout pHIFU exposure: it was sporadic in vivo, but ex vivo it decreased rapidly and stopped over the first few pulses. Cavitation activity depended on the interplay between the destruction and circulation of cavitation nuclei, which are not only used up by HIFU treatment but also replenished or carried away by circulation in vivo. These findings are important for treatment planning and optimization in pHIFU-induced drug delivery, in particular for pancreatic tumors.
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影响因子：
2.4
作者：
Khokhlova, Tatiana D.;Canney, Michael S.;Bailey, Michael R.
通讯作者：
Bailey, Michael R.
影响因子：
3.9
作者：
Ahearne, M;Yang, Y;Liu, KK
通讯作者：
Liu, KK
DOI：
10.1109/58.139123
发表时间：
1992-03-01
影响因子：
3.6
作者：
JENSEN, JA;SVENDSEN, NB
通讯作者：
SVENDSEN, NB
影响因子：
2.9
作者：
Church, CC
通讯作者：
Church, CC
影响因子：
2.4
作者：
Khokhlova, VA;Bailey, MR;Crum, LA
通讯作者：
Crum, LA