用于质子范围验证的相变超声造影剂:向活体应用迈进。

IF 3.3 3区 医学 Q2 ENGINEERING, BIOMEDICAL Physics in medicine and biology Pub Date : 2024-10-10 DOI:10.1088/1361-6560/ad7e76
Bram Carlier, Sophie V Heymans, Gonzalo Collado-Lara, Luigi Musetta, Marcus Ingram, Yosra Toumia, Gaio Paradossi, Hendrik J Vos, Tania Roskams, Jan D'hooge, Koen Van Den Abeele, Edmond Sterpin, Uwe Himmelreich
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引用次数: 0

摘要

目的:在质子治疗中,质子束的深度剂量特性优于传统的光子放疗,但范围的不确定性阻碍了质子治疗的最佳效益。为了减少这些不确定性,我们最近提出使用相变超声造影剂作为一种经济有效的范围验证工具。特别是,过热的纳米液滴在质子照射时可转化为回声微气泡,由此产生的超声对比度与质子射程相关,具有很高的再现性。首先,使用几种比色法研究了对辐射敏感的聚乙烯醇全氟丁烷纳米液滴的体内生物相容性。然后,在健康的 Sprague Dawley 大鼠体内使用声学液滴汽化法和不同能量(49.7 MeV 和 62 MeV)的质子束辐照法对体内超声对比度进行了表征。利用声学液滴气化法以及生理学监测和组织学相结合的方法,对纳米液滴的生物相容性进行了初步评估。在健康大鼠体内,静脉注射的纳米微滴主要积聚在网状内皮系统器官中,在这些器官中产生的超声造影剂的寿命(< 30 分钟)与典型的放射治疗时间(< 5 分钟)相符。液滴自发汽化不会产生明显的背景信号。对注射液滴的大鼠肝脏进行的在线超声成像表明,质子响应与能量有关,可通过改变纳米液滴浓度来调节。不过,在决定纳米液滴的确切剂量方案时必须谨慎,因为在声学液滴汽化后观察到了轻微的生理反应(心率下降、肉芽肿形成) 意义。这些发现强调了相变超声造影剂在验证体内质子范围方面的潜力,并为最终的临床应用提供了下一步的依据 意义。
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Phase-change ultrasound contrast agents for proton range verification: towards anin vivoapplication.

Objective.In proton therapy, range uncertainties prevent optimal benefit from the superior depth-dose characteristics of proton beams over conventional photon-based radiotherapy. To reduce these uncertainties we recently proposed the use of phase-change ultrasound contrast agents as an affordable and effective range verification tool. In particular, superheated nanodroplets can convert into echogenic microbubbles upon proton irradiation, whereby the resulting ultrasound contrast relates to the proton range with high reproducibility. Here, we provide a firstin vivoproof-of-concept of this technology.Approach.First, thein vitrobiocompatibility of radiation-sensitive poly(vinyl alcohol) perfluorobutane nanodroplets was investigated using several colorimetric assays. Then,in vivoultrasound contrast was characterized using acoustic droplet vaporization (ADV) and later using proton beam irradiations at varying energies (49.7 MeV and 62 MeV) in healthy Sprague Dawley rats. A preliminary evaluation of thein vivobiocompatibility was performed using ADV and a combination of physiology monitoring and histology.Main results.Nanodroplets were non-toxic over a wide concentration range (<1 mM). In healthy rats, intravenously injected nanodroplets primarily accumulated in the organs of the reticuloendothelial system, where the lifetime of the generated ultrasound contrast (<30 min) was compatible with a typical radiotherapy fraction (<5 min). Spontaneous droplet vaporization did not result in significant background signals. Online ultrasound imaging of the liver of droplet-injected rats demonstrated an energy-dependent proton response, which can be tuned by varying the nanodroplet concentration. However, caution is warranted when deciding on the exact nanodroplet dose regimen as a mild physiological response (drop in cardiac rate, granuloma formation) was observed after ADV.Significance.These findings underline the potential of phase-change ultrasound contrast agents forin vivoproton range verification and provide the next step towards eventual clinical applications.

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来源期刊
Physics in medicine and biology
Physics in medicine and biology 医学-工程:生物医学
CiteScore
6.50
自引率
14.30%
发文量
409
审稿时长
2 months
期刊介绍: The development and application of theoretical, computational and experimental physics to medicine, physiology and biology. Topics covered are: therapy physics (including ionizing and non-ionizing radiation); biomedical imaging (e.g. x-ray, magnetic resonance, ultrasound, optical and nuclear imaging); image-guided interventions; image reconstruction and analysis (including kinetic modelling); artificial intelligence in biomedical physics and analysis; nanoparticles in imaging and therapy; radiobiology; radiation protection and patient dose monitoring; radiation dosimetry
期刊最新文献
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