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
{"title":"用于质子范围验证的相变超声造影剂:向活体应用迈进。","authors":"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","doi":"10.1088/1361-6560/ad7e76","DOIUrl":null,"url":null,"abstract":"<p><p><i>Objective.</i>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 first<i>in vivo</i>proof-of-concept of this technology.<i>Approach.</i>First, the<i>in vitro</i>biocompatibility of radiation-sensitive poly(vinyl alcohol) perfluorobutane nanodroplets was investigated using several colorimetric assays. Then,<i>in vivo</i>ultrasound 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 the<i>in vivo</i>biocompatibility was performed using ADV and a combination of physiology monitoring and histology.<i>Main results.</i>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.<i>Significance.</i>These findings underline the potential of phase-change ultrasound contrast agents for<i>in vivo</i>proton range verification and provide the next step towards eventual clinical applications.</p>","PeriodicalId":20185,"journal":{"name":"Physics in medicine and biology","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Phase-change ultrasound contrast agents for proton range verification: towards an<i>in vivo</i>application.\",\"authors\":\"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\",\"doi\":\"10.1088/1361-6560/ad7e76\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><i>Objective.</i>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 first<i>in vivo</i>proof-of-concept of this technology.<i>Approach.</i>First, the<i>in vitro</i>biocompatibility of radiation-sensitive poly(vinyl alcohol) perfluorobutane nanodroplets was investigated using several colorimetric assays. Then,<i>in vivo</i>ultrasound 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 the<i>in vivo</i>biocompatibility was performed using ADV and a combination of physiology monitoring and histology.<i>Main results.</i>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.<i>Significance.</i>These findings underline the potential of phase-change ultrasound contrast agents for<i>in vivo</i>proton range verification and provide the next step towards eventual clinical applications.</p>\",\"PeriodicalId\":20185,\"journal\":{\"name\":\"Physics in medicine and biology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-10-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Physics in medicine and biology\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1088/1361-6560/ad7e76\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENGINEERING, BIOMEDICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Physics in medicine and biology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1088/1361-6560/ad7e76","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
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.
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