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用于小动物抗癌药物疗效临床前测试的环形相控阵换能器。

Annular phased array transducer for preclinical testing of anti-cancer drug efficacy on small animals.

作者信息

Kujawska Tamara, Secomski Wojciech, Byra Michał, Postema Michiel, Nowicki Andrzej

机构信息

Department of Ultrasound, Institute of Fundamental Technological Research, Polish Academy of Sciences, Pawińskiego 5b, 02-106 Warsaw, Poland.

Department of Ultrasound, Institute of Fundamental Technological Research, Polish Academy of Sciences, Pawińskiego 5b, 02-106 Warsaw, Poland.

出版信息

Ultrasonics. 2017 Apr;76:92-98. doi: 10.1016/j.ultras.2016.12.008. Epub 2016 Dec 12.

Abstract

A technique using pulsed High Intensity Focused Ultrasound (HIFU) to destroy deep-seated solid tumors is a promising noninvasive therapeutic approach. A main purpose of this study was to design and test a HIFU transducer suitable for preclinical studies of efficacy of tested, anti-cancer drugs, activated by HIFU beams, in the treatment of a variety of solid tumors implanted to various organs of small animals at the depth of the order of 1-2cm under the skin. To allow focusing of the beam, generated by such transducer, within treated tissue at different depths, a spherical, 2-MHz, 29-mm diameter annular phased array transducer was designed and built. To prove its potential for preclinical studies on small animals, multiple thermal lesions were induced in a pork loin ex vivo by heating beams of the same: 6W, or 12W, or 18W acoustic power and 25mm, 30mm, and 35mm focal lengths. Time delay for each annulus was controlled electronically to provide beam focusing within tissue at the depths of 10mm, 15mm, and 20mm. The exposure time required to induce local necrosis was determined at different depths using thermocouples. Location and extent of thermal lesions determined from numerical simulations were compared with those measured using ultrasound and magnetic resonance imaging techniques and verified by a digital caliper after cutting the tested tissue samples. Quantitative analysis of the results showed that the location and extent of necrotic lesions on the magnetic resonance images are consistent with those predicted numerically and measured by caliper. The edges of lesions were clearly outlined although on ultrasound images they were fuzzy. This allows to conclude that the use of the transducer designed offers an effective noninvasive tool not only to induce local necrotic lesions within treated tissue without damaging the surrounding tissue structures but also to test various chemotherapeutics activated by the HIFU beams in preclinical studies on small animals.

摘要

一种使用脉冲高强度聚焦超声(HIFU)来破坏深部实体肿瘤的技术是一种很有前景的非侵入性治疗方法。本研究的主要目的是设计并测试一种HIFU换能器,该换能器适用于对经HIFU束激活的受试抗癌药物在治疗植入小动物不同器官、位于皮下1 - 2厘米深度左右的各种实体肿瘤的疗效进行临床前研究。为了使这种换能器产生的波束能够在不同深度的治疗组织内聚焦,设计并制造了一个直径29毫米、2兆赫兹的球形环形相控阵换能器。为了证明其在小动物临床前研究中的潜力,通过相同的6瓦、12瓦或18瓦声功率以及25毫米、30毫米和35毫米焦距的加热波束在离体猪里脊肉中诱导出多个热损伤。对每个环的时间延迟进行电子控制,以在10毫米、15毫米和20毫米深度的组织内实现波束聚焦。使用热电偶确定在不同深度诱导局部坏死所需的暴露时间。将数值模拟确定的热损伤位置和范围与使用超声和磁共振成像技术测量的结果进行比较,并在切割受试组织样本后用数字卡尺进行验证。结果的定量分析表明,磁共振图像上坏死病变的位置和范围与数值预测和卡尺测量的结果一致。病变边缘在磁共振图像上清晰勾勒,但在超声图像上模糊不清。由此可以得出结论,所设计的换能器的使用不仅提供了一种有效的非侵入性工具,可在不损伤周围组织结构的情况下在治疗组织内诱导局部坏死病变,而且还可在小动物临床前研究中测试由HIFU束激活的各种化疗药物。

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