Tackling physics challenges of conformal small animal image guided radiotherapy

应对适形小动物图像引导放射治疗的物理挑战

• 批准号: RGPIN-2016-04055
• 负责人: Bazalova, Magdalena
• 金额: $ 2.33万
• 依托单位: University of Victoria
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=708979
• 关键词: Tackling; physics; challenges; conformal; small

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.

功能化的纳米颗粒已显示为合适的癌症成像对比剂和治疗剂。然而，尚未对纳米颗粒使用与放射疗法结合使用的潜力尚未得到充分检查，并且主要通过癌细胞研究进行了研究。细胞研究表明，在纳米颗粒存在下传递的辐射在杀死癌细胞方面比单独放疗更有效。尽管这一重要发现可能会导致副作用减少的治疗结果改善，但在可以考虑使用纳米颗粒进行临床试验的放射疗法之前，必须首先研究其在小动物中的作用。 我建议使用一种新型的X射线成像技术在纳米颗粒图像指导下进行准确的辐射递送，以开发一种独特的小动物放射疗法系统，该系统将对基于纳米颗粒的癌症进行严格研究。 1）我将设计设备并开发程序，以确保与保形小动物辐照器的准确放疗。近年来已经开发了保形小动物放射疗法的设备，但尚未开发其校准程序。通过在世界各地众多机构进行的详细计算机模拟和系统实验，我将设计硬件和软件，以确保准确的放疗，以尽可能地模仿临床放射疗法。 2）我将设计一个新型的小型动物X射线成像系统，用于可视化纳米颗粒，并将其与保形的小动物辐照器集成在一起。我将使用计算机仿真来优化X射线荧光计算机断层扫描（XFCT）成像，该成像显示出低浓度成像纳米颗粒的希望，但由于较长的成像时间，从未用于小型动物研究。我将通过添加检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。我将在实验桌系统上测试优化的XFCT系统，然后将其集成到保形小动物辐照器上。具有不同大小和不同纳米颗粒的测试对象的成像实验将在模拟和实验阶段进行。 成功完成拟议的研究后，我将建立一个独特的放射疗法系统，该系统将使基于纳米颗粒的癌症放射疗法的小动物研究。该系统将适用于加拿大和世界各地的科学家，它将成为将基于纳米颗粒的癌症治疗转化为诊所的宝贵工具。此外，我将通过培训MSC和博士学位的学生提供高素质的人员，他们将成为辐射物理学专家，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。