Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, Seattle, WA, USA.
Ultrasound Med Biol. 2013 Mar;39(3):424-38. doi: 10.1016/j.ultrasmedbio.2012.10.012. Epub 2013 Jan 11.
Recent studies have shown that shockwave heating and millisecond boiling in high-intensity focused ultrasound fields can result in mechanical fractionation or emulsification of tissue, termed boiling histotripsy. Visual observations of the change in color and contents indicated that the degree of thermal damage in the emulsified lesions can be controlled by varying the parameters of the exposure. The goal of this work was to examine thermal and mechanical effects in boiling histotripsy lesions using histologic and biochemical analysis. The lesions were induced in ex vivo bovine heart and liver using a 2-MHz single-element transducer operating at duty factors of 0.005-0.01, pulse durations of 5-500 ms and in situ shock amplitude of 73 MPa. Mechanical and thermal damage to tissue was evaluated histologically using conventional staining techniques (hematoxylin and eosin, and nicotinamide adenine dinucleotide-diaphorase). Thermal effects were quantified by measuring denaturation of salt soluble proteins in the treated region. According to histologic analysis, the lesions that visually appeared as a liquid contained no cellular structures larger than a cell nucleus and had a sharp border of one to two cells. Both histologic and protein analysis showed that lesions obtained with short pulses (<10 ms) did not contain any thermal damage. Increasing the pulse duration resulted in an increase in thermal damage. However, both protein analysis and nicotinamide adenine dinucleotide-diaphorase staining showed less denaturation than visually observed as whitening of tissue. The number of high-intensity focused ultrasound pulses delivered per exposure did not change the lesion shape or the degree of thermal denaturation, whereas the size of the lesion showed a saturating behavior suggesting optimal exposure duration. This study confirmed that boiling histotripsy offers an effective, predictable way to non-invasively fractionate tissue into sub-cellular fragments with or without inducing thermal damage.
最近的研究表明，高强度聚焦超声场中的冲击波加热和毫秒级沸腾可导致组织的机械分割或乳化，称为沸腾空化爆破。通过观察颜色和内容的变化，可以发现通过改变暴露参数可以控制乳化病变中的热损伤程度。这项工作的目的是使用组织学和生化分析来检查沸腾空化爆破病变中的热和机械效应。使用 2MHz 单阵元换能器在占空比为 0.005-0.01、脉冲持续时间为 5-500ms 和原位冲击波幅度为 73MPa 的条件下，在离体牛心和肝中诱导病变。使用常规染色技术（苏木精和伊红、烟酰胺腺嘌呤二核苷酸-黄递酶）评估组织的机械和热损伤。通过测量处理区域中盐溶性蛋白质的变性来定量热效应。根据组织学分析，肉眼观察呈液体的病变中没有大于细胞核的细胞结构，并且边界清晰，只有一到两个细胞宽。组织学和蛋白质分析均表明，短脉冲（<10ms）获得的病变不包含任何热损伤。增加脉冲持续时间会导致热损伤增加。然而，蛋白质分析和烟酰胺腺嘌呤二核苷酸-黄递酶染色均显示，与肉眼观察到的组织变白相比，变性程度较低。每次暴露传递的高强度聚焦超声脉冲数不会改变病变形状或热变性程度，而病变大小表现出饱和行为，表明最佳暴露持续时间。这项研究证实，沸腾空化爆破提供了一种有效且可预测的方法，可以将组织非侵入性地分割成亚细胞碎片，而无需诱导热损伤。
