An Ionizing Radiation Acoustics Imaging (iRAI) Approach for guided Flash Radiotherapy

摘要 一种利用超高剂量率的新兴放射治疗(RT)方式，称为闪光放射治疗，已经 在临床前研究和早期临床中显示出前所未有的提高放射治疗比率的能力 案子。由于缺乏适当的图像引导技术，这些研究一直局限于肤浅 辐射和允许使用现有方法监测提供剂量的简单化情况。这 严重阻碍了闪光放射治疗的前景，并在很大程度上限制了其对深层次肿瘤的前景影响， 它们构成了大多数RT癌症病例。人们普遍认为，目前使用的剂量测量技术 缺乏在不暴露的情况下在实际临床环境中提供闪光放射治疗的必要指导 患者面临的巨大风险远远超出了传统的RT分娩。毫无疑问，有一个未得到满足的 需要开发体内图像引导技术来保障闪光RT的准确传递。我们认为这些 挑战可以通过完善新兴的电离辐射诱导声成像技术来解决 (Irai)，它可以与Flash-RT传送系统本质上配对。Irai是基于已知的 辐射物理中的热声现象，其中声波是由热弹性产生的 物质在吸收穿透的脉动高能辐射后的膨胀。建立在我们的 多机构多学科团队，在超声(美国)成像、RT物理、数据分析、 和我们有希望的初步结果，我们假设：(1)由以下组成的双模式成像系统 IRAI和US(IRAI-US)可以同时成像组织形态和3D剂量沉积 具有高时空分辨率的Flash-RT传送；以及(2)基于机器学习的重建和 异常检测可以有效地提高成像质量，减少误差，为临床提供参考 翻译。因此，在这个项目中，我们的目标是开发Irai-US和Machine的技术潜力 学习开发有效和安全的Flash-RT交付的图像引导平台。我们会 使用计算机模拟(在硅胶中)、组织模拟来展示其对电子束和质子束的有效性 幻影，以及相关的临床前活体模型。具体地说，我们将(1)开发和测试双模成像 闪光-RT三维辐射-声学剂量测量和超声成像系统；(2)体内评价 在电子和质子闪光-RT传输期间irai-US双重成像的性能；以及(3)适应和 使用Depth改进闪存-RT的irai体表示、时间分辨率和错误检测 机器学习算法(DeepRAI)走向有效的临床实施。 影响：我们建议的映像引导闪存RT一旦得到验证，将提供实用、健壮、经济高效的 和独特的系统，以保护闪存-RT交付。这些进展将解决当前 阻碍Flash-RT临床翻译的挑战并使其能够实现限制的承诺 放射治疗对正常组织有毒性，从而改善癌症患者的护理和生活质量。

SUMMARY An emerging radiotherapy (RT) modality that utilizes ultra-high dose rate, known as FLASH-RT, has demonstrated unprecedented ability for improving RT therapeutic ratio in preclinical studies and early clinical cases. Because of lack of appropriate image-guidance technologies, these studies have been limited to superficial irradiations and simplistic cases where monitoring of delivered dose is permissible using existing methods. This severely handicaps the prospects of FLASH-RT and largely limits its promising impact for deep seated tumors, which constitute most of RT cancer cases. It is widely recognized that currently used dosimetry technologies fall short of providing the necessary guidance to deliver FLASH-RT in a practical clinical setting without exposing the patient to tremendous risks that go far beyond the traditional RT delivery. Undoubtedly, there is an unmet need to develop in vivo image-guidance techniques to safeguard FLASH-RT accurate delivery. We hold that these challenges can be resolved by refining the emerging technology of ionizing radiation-induced acoustic imaging (iRAI), which can be intrinsically paired with FLASH-RT delivery systems. iRAI is based on the known thermoacoustic phenomenon in radiation physics, where acoustic waves are generated from thermoelastic expansion of a substance following absorption of penetrating pulsated high energy radiation. Building upon our multi-institutional multidisciplinary team with expertise in ultrasound (US) imaging, RT physics, data analytics, and our promising preliminary results, we hypothesize that: (1) a dual-modality imaging system comprised of iRAI and US (iRAI-US) can simultaneously image both tissue morphology and 3D dose deposition during FLASH-RT delivery with high spatio-temporal resolutions; and (2) machine learning based reconstruction and anomaly detection can effectively improve imaging quality and mitigate errors, respectively, for clinical translation. Therefore, in this project we aim to exploit the technological potentials of iRAI-US and machine learning for developing an image-guidance platform for effective and safe FLASH-RT delivery. We will demonstrate its efficacy with electron and proton beams using computer simulations (in silico), tissue mimicking phantoms, and relevant preclinical in vivo models. Specifically, we will (1) develop and test a dual-mode imaging system for 3D radiation-acoustics dosimetry and US imaging for FLASH-RT; (2) evaluate the in vivo performance of iRAI-US dual imaging during electron and proton FLASH-RT deliveries; and (3) adapt and improve iRAI volumetric representation, temporal resolution and error detection for FLASH-RT using deep machine learning algorithms (DeepRAI) towards effective clinical implementation. Impact: Our proposed image-guided FLASH-RT, once validated, will offer a practical, robust, cost-effective, and unique system for safeguarding FLASH-RT delivery. These advancements will address the current challenges impeding the clinical translation of FLASH-RT and enable achieving its promise of limiting radiotherapy toxicity to normal tissues and thereby improving cancer patient care and quality of life.