Technologies enabling in vivo range verification during proton therapy are actively sought as a means to reduce the clinical safety margins currently adopted to avoid tumor underdosage. In this contribution, we applied the semi-empirical theory of radiation-induced vaporization of superheated liquids to coated nanodroplets. Nanodroplets are injectable phase-change contrast agents that can vaporize into highly echogenic microbubbles to provide contrast in ultrasound images. We exposed nanodroplet dispersions in aqueous phantoms to monoenergetic proton beams of varying energies and doses. Ultrasound imaging of the phantoms revealed that radiation-induced droplet vaporization occurred in regions proximal to the proton Bragg peak. A statistically significant increase in contrast was observed in irradiated regions for doses as low as 2 Gy and found to be proportional to the proton fluence. The absence of enhanced response in the vicinity of the Bragg peak, combined with theoretical considerations, suggest that droplet vaporization is induced by high linear energy transfer (LET) recoil ions produced by nuclear reactions with incoming protons. Vaporization profiles were compared to non-elastic cross sections and LET characteristics of oxygen recoils. Shifts between the ultrasound image contrast drop and the expected proton range showed a sub-millimeter reproducibility. These early findings confirm the potential of superheated nanodroplets as a novel tool for proton range verification.

中文翻译：

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使用可注射的辐射敏感纳米液滴通过超声成像对质子范围进行验证：可行性研究。

积极寻求能够在质子治疗期间进行体内范围验证的技术，以减少目前为避免肿瘤剂量不足而采用的临床安全范围。在这项贡献中，我们将辐射诱发的过热液体汽化的半经验理论应用于涂层纳米液滴。纳米液滴是可注射的相变造影剂，可蒸发成高度回声的微气泡，以在超声图像中提供对比度。我们将水模体中的纳米液滴分散体暴露于能量和剂量不同的单能质子束中。体模的超声成像显示，辐射引起的液滴蒸发发生在质子布拉格峰附近的区域。对于低至2 Gy的剂量，在受辐照区域中观察到对比度的统计学显着增加，并且发现与质子注量成正比。在布拉格峰附近没有增强的响应，再加上理论上的考虑，表明液滴的汽化是由与传入质子的核反应产生的高线性能量转移（LET）反冲离子引起的。将蒸发曲线与非弹性横截面和氧气反冲的LET特性进行了比较。超声图像对比度下降和预期质子范围之间的转换显示了亚毫米的可重复性。这些早期发现证实了过热的纳米液滴作为质子范围验证的新工具的潜力。在布拉格峰附近没有增强的响应，再加上理论上的考虑，表明液滴的汽化是由与传入质子的核反应产生的高线性能量转移（LET）反冲离子引起的。将蒸发曲线与非弹性横截面和氧气反冲的LET特性进行了比较。超声图像对比度下降和预期质子范围之间的转换显示了亚毫米的可重复性。这些早期发现证实了过热的纳米液滴作为质子范围验证的新工具的潜力。在布拉格峰附近没有增强的响应，再加上理论上的考虑，表明液滴的汽化是由与传入质子的核反应产生的高线性能量转移（LET）反冲离子引起的。将蒸发曲线与非弹性横截面和氧气反冲的LET特性进行了比较。超声图像对比度下降和预期质子范围之间的转换显示了亚毫米的可重复性。这些早期发现证实了过热的纳米液滴作为质子范围验证的新工具的潜力。将蒸发曲线与非弹性横截面和氧气反冲的LET特性进行了比较。超声图像对比度下降和预期质子范围之间的转换显示了亚毫米的可重复性。这些早期发现证实了过热的纳米液滴作为质子范围验证的新工具的潜力。将蒸发曲线与非弹性横截面和氧气反冲的LET特性进行了比较。超声图像对比度下降和预期质子范围之间的转换显示了亚毫米的可重复性。这些早期发现证实了过热的纳米液滴作为质子范围验证的新工具的潜力。