Tackling physics challenges of conformal small animal image guided radiotherapy

功能化纳米颗粒已显示出作为一种合适的癌症成像造影剂和治疗剂的前景。然而，纳米颗粒与放射治疗联合使用的潜力尚未得到充分研究，主要是通过癌细胞研究进行调查。细胞研究表明，在纳米粒子存在的情况下进行的辐射比单独的放射治疗更有效地杀死癌细胞。虽然这一重要发现可能会改善治疗效果并减少副作用，但在考虑将纳米颗粒放射治疗用于临床试验之前，必须首先研究其在小动物中的作用。***我建议开发一种独特的小动物放疗系统，能够在纳米颗粒图像引导下使用新型x射线成像技术进行精确的辐射输送，这将使基于纳米颗粒的癌症放疗的严谨研究成为可能。***1)我将设计设备和开发程序，以确保使用适形小动物照射器进行准确的放射治疗。近年来，小动物适形放射治疗装置已经开发出来，但其校准程序尚未开发。通过在世界各地众多机构进行的详细的计算机模拟和系统的实验，我将设计硬件和软件，以确保尽可能接近临床放疗的精确放疗。***2)我将设计一种新型的小动物x射线成像系统，用于纳米颗粒的可视化，并将其与保形小动物辐照器集成。我将使用计算机模拟来优化x射线荧光计算机断层扫描（XFCT）成像，该成像在低浓度的纳米颗粒中显示出前景，但由于成像时间长，从未用于小动物研究。我将通过增加探测器和开发更复杂的数据采集和图像重建技术来减少成像时间。我将在实验桌面系统上测试优化后的XFCT系统，然后将其集成到保形小动物辐照器上。在模拟和实验两个阶段，将对不同尺寸和不同纳米颗粒的测试对象进行成像实验。***在成功完成拟议的研究后，我将建立一个独特的放疗系统，将使基于纳米颗粒的癌症放疗的小动物研究成为可能。该系统将提供给加拿大和世界各地的科学家，它将成为将纳米粒子为基础的癌症治疗转化为临床的宝贵工具。此外，我将通过培养硕士和博士水平的学生提供高素质的人才，他们将成为辐射物理专家，并将成为加拿大癌症中心和医疗设备工程公司的宝贵资产。********

Functionalized nanoparticles have shown promise as a suitable cancer imaging contrast agent as well as therapeutic agent. However, the potential for nanoparticle use in combination with radiotherapy has not been fully examined and has been primarily investigated by means of cancer cell studies. Cell studies have demonstrated that radiation delivered in the presence of nanoparticles was more effective in killing cancer cells than radiotherapy alone. While this important finding could potentially result in improved treatment outcomes with reduced side effects, before radiotherapy with nanoparticles can be considered for clinical trials, its effects in small animals must first be investigated.***I propose to develop a unique small animal radiotherapy system capable of accurate radiation delivery under nanoparticle image guidance using a novel x-ray imaging technique, which will enable rigorous studies of nanoparticle-based radiotherapy of cancer.***1) I will design equipment and develop procedures assuring accurate radiotherapy delivery with conformal small animal irradiators. Devices for conformal small animal radiotherapy have been developed in recent years but their calibration procedure has not been developed. By means of detailed computer simulations and systematic experiments conducted at numerous institutions around the world, I will design hardware and software to assure accurate radiotherapy that mimics clinical radiotherapy as closely as possible.***2) I will design a novel small animal x-ray imaging system for visualization of nanoparticles and I will integrate it with a conformal small animal irradiator. I will use computer simulations to optimize x-ray fluorescence computed tomography (XFCT) imaging that shows promise in imaging nanoparticles in low concentrations, but has never been used for small animal studies due to the long imaging times. I will decrease imaging times by adding detectors and by developing more sophisticated data acquisition and image reconstruction techniques. I will test the optimized XFCT system on an experimental tabletop system before integrating it on a conformal small animal irradiator. Imaging experiments with test objects of different sizes and with different nanoparticles will be performed in both the simulation and experimental phases.***Upon successful completion of the proposed research, I will have built a unique radiotherapy system that will enable small animal studies of nanoparticle-based cancer radiotherapy. The system will be available to scientists in Canada and around the world and it will become an invaluable tool for translation of nanoparticle-based cancer therapy into the clinic. Moreover, I will provide highly qualified personnel by training MSc- and PhD-level students, who will become experts in radiation physics and who will be valuable assets for Canadian cancer centres and medical device engineering companies.********