Holographic Focused Ultrasound Hyperthermia System for Uniform Simultaneous Thermal Exposure of Multiple Tumor Spheroids.
Holographic Focused Ultrasound Hyperthermia System for Uniform Simultaneous Thermal Exposure of Multiple Tumor Spheroids.
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声全息图作为一种方法，同时提供控制超声热疗多个肿瘤球体进行了研究。研究结果表明，设计用于提供均匀热剂量而不是均匀声场的全息透镜可以调整换能器的自然焦点，允许同时暴露于多个肿瘤球体的超声介导的热疗，并提高未来研究的实验吞吐量。初步的体外研究结果表明，超声波和聚合酶链式反应加热提供的热疗有不同的结果，超声波是更致命的相同的热剂量。热疗目前用于治疗癌症，因为它具有放射和化学敏化以及刺激免疫反应的能力。虽然超声波是非电离的，并且可以非侵入性地在身体深处诱导热疗，但实现均匀和体积的热疗是具有挑战性的。本文提出了一种基于3D打印声全息图的聚焦超声热疗系统，该系统结合高强度聚焦超声（HIFU）换能器在多个目标中产生均匀的等温剂量。该系统的设计目的是处理包含在国际电工委员会（IEC）组织模拟体模中的几个3D细胞聚集体，该体模具有多个威尔斯孔，每个孔容纳单个肿瘤球体，并进行实时温度和热剂量监测。使用声学和热方法验证系统性能，最终在三个威尔斯井中产生的热剂量差异小于4%。在体外测试了该系统在43 °C（CEM 43）下向U87-MG胶质瘤细胞的球状体输送0-120累积等效分钟的热剂量。超声波诱导加热对这些球体的生长的影响进行了比较加热使用聚合酶链反应（PCR）热循环仪。结果显示，将U87-MG球状体暴露于120 CEM 43的超声诱导热剂量使它们缩小了15%，并且比暴露于热循环仪诱导的加热中的那些减少了它们的生长和代谢活性。这种修改HIFU换能器以提供超声热疗的低成本方法为使用定制的声学全息图精确控制向复杂治疗目标的热剂量递送开辟了新的途径。球体数据表明，热和非热机制涉及癌细胞对非消融性超声加热的响应。
Acoustic holograms were investigated as a method of delivering simultaneously controlled ultrasound hyperthermia to multiple tumor spheroids. Findings show that holographic lenses designed to deliver a uniform thermal dose rather than a uniform acoustic field can tune the natural focus of a transducer, allowing the exposure to ultrasound-mediated hyperthermia of several tumor spheroids simultaneously, and improving experimental throughput for future studies. Preliminary in-vitro findings suggest that hyperthermia delivered by ultrasound and polymerase chain reaction heating have different outcomes, with ultrasound being more lethal for the same thermal dose. Hyperthermia is currently used to treat cancer due to its ability to radio- and chemo-sensitize and to stimulate the immune response. While ultrasound is non-ionizing and can induce hyperthermia deep within the body non-invasively, achieving uniform and volumetric hyperthermia is challenging. This work presents a novel focused ultrasound hyperthermia system based on 3D-printed acoustic holograms combined with a high-intensity focused ultrasound (HIFU) transducer to produce a uniform iso-thermal dose in multiple targets. The system is designed with the aim of treating several 3D cell aggregates contained in an International Electrotechnical Commission (IEC) tissue-mimicking phantom with multiple wells, each holding a single tumor spheroid, with real-time temperature and thermal dose monitoring. System performance was validated using acoustic and thermal methods, ultimately yielding thermal doses in three wells that differed by less than 4%. The system was tested in vitro for delivery of thermal doses of 0–120 cumulative equivalent minutes at 43 °C (CEM43) to spheroids of U87-MG glioma cells. The effects of ultrasound-induced heating on the growth of these spheroids were compared with heating using a polymerase chain reaction (PCR) thermocycler. Results showed that exposing U87-MG spheroids to an ultrasound-induced thermal dose of 120 CEM43 shrank them by 15% and decreased their growth and metabolic activity more than seen in those exposed to a thermocycler-induced heating. This low-cost approach of modifying a HIFU transducer to deliver ultrasound hyperthermia opens new avenues for accurately controlling thermal dose delivery to complex therapeutic targets using tailored acoustic holograms. Spheroid data show that thermal and non-thermal mechanisms are implicated in the response of cancer cells to non-ablative ultrasound heating.
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影响因子：
4.6
作者：
Fushimi T;Yamamoto K;Ochiai Y
通讯作者：
Ochiai Y
影响因子：
9.5
作者：
Kaczmarek, Katarzyna;Hornowski, Tomasz;Jozefczak, Arkadiusz
通讯作者：
Jozefczak, Arkadiusz
DOI：
10.6028/jres.097.013
发表时间：
1992-05
影响因子：
1.5
作者：
Jones FE;Harris GL
通讯作者：
Harris GL
DOI：
10.1186/s40349-018-0115-5
发表时间：
2018-08-13
期刊：
JOURNAL OF THERAPEUTIC ULTRASOUND
影响因子：
--
作者：
Ozhinsky, Eugene;Salgaonkar, Vasant A.;Rieke, Viola
通讯作者：
Rieke, Viola
影响因子：
4
作者：
Andres, Diana;Vappou, Jonathan;Camarena, Francisco
通讯作者：
Camarena, Francisco