Development of intensity modulated radiation therapy for small animal research

摘要 临床前放射生物学研究的临床相关性取决于其复制能力 最先进的人类治疗方法，已实现高靶向精度和剂量 基于技术突破的适形性，包括调强放射治疗 （IMRT）和图像引导放射治疗（IGRT）。尽管临床前研究的最新进展 辐射器提供IGRT和更准确的剂量计算，一个至关重要的 现代放射治疗的组成部分，IMRT，仍然缺失。在没有IMRT的情况下， 不能代表最先进的人类治疗的剂量测定质量，特别是 目前的趋势是采用更复杂、凹形或同时增强的剂量分布。 因此，从动物研究和人体试验中成功转化的情况很少。 先前开发IMRT和更好地模拟最先进的人类放射治疗的努力已经失败。 不成功的原因是难以使多叶准直器（MLC）准直并提供 规划系统，是直观的生物学家使用。为了克服这些挑战，我们将 为波束方向选择和矩形孔径开发全局凸优化器 优化，因此可以自动有效地创建高质量的IMRT治疗计划 仅使用矩形孔。然后，我们提出了一种新的小动物调强放射治疗剂量调制器 通过计划优化的突破，有效地提供不妥协的IMRT计划 具有比理论上小型化的MLC更高的可实现的分辨率。我们将使 硬件设计和软件开源的研究社区。为了实现目标，我们 提出以下目标：目标1。开发临床前治疗计划系统， 自动选择光束方向，并使用多个 矩形孔。目标二。稀疏正交准直器（SOC）的设计、制作和验证 以提供优化的矩形段。

Abstract The clinical relevance of preclinical radiobiological studies depends on their ability to replicate state-of-the-art human treatments, which have achieved high targeting accuracy and dose conformality based on technological breakthroughs including intensity modulated radiotherapy (IMRT) and image guided radiotherapy (IGRT). Despite recent developments in preclinical irradiators for providing IGRT and more accurate dose calculations, a critically important component in modern radiotherapy, IMRT, is still missing. Without IMRT, the animal studies are unable to represent the dosimetric quality of state of the art human treatments, particularly with current trend of employing more complex, concave or simultaneously boosted dose distributions. As a result, successful translation from animal studies and human trial is rare. Previous efforts to develop IMRT and better mimic state of the art human radiotherapy have been unsuccessful due to the difficulty of miniaturizing multileaf collimator (MLC) and providing a planning system that is intuitive to use by biologists. To overcome these challenges, we will develop a global convex optimizer for beam orientation selection and rectangular aperture optimization so high quality IMRT treatment plans can be automatically and efficiently created using only rectangular apertures. We then propose a novel small animal IMRT dose modulator enabled by a breakthrough in plan optimization to efficiently deliver uncompromised IMRT plans with higher achievable resolution than a theoretically miniaturized MLC. We will make the hardware design and software open source to the research community. To achieve the goal, we propose the following aims: Aim 1. Develop a preclinical treatment planning system that automatically selects beam orientations and optimizes intensity modulation using multiple rectangular apertures. Aim 2. Design, fabricate and validate a sparse orthogonal collimator (SOC) to deliver the optimized rectangular segments.