A small animal radiation research and multi-spectral optoacoustic tomography facility for advancing the physics and engineering of novel radiotherapy

放射治疗（RT）是癌症治疗中最有效的工具之一，临床RT随着交付和治疗计划的技术进步而不断发展。现代RT的一个关键组成部分是增强的图像引导，需要精确的肿瘤靶向，治疗监测和治疗评估。为了实现对接受RT的癌症患者的最佳护理，需要开发优化图像引导的物理和技术。这应该包括利用靶向药物和纳米颗粒的新发现，增加肿瘤对辐射的敏感性，以及RT和其他物理疗法（如高强度聚焦超声（HIFU），高热和超声（US）微泡损伤肿瘤血管系统）之间的协同作用。在最有前途的技术可以转化为临床研究之前，这些新的图像引导RT方法必须首先在临床前环境中进行研究。对于这项工作，最佳临床前治疗与最佳临床前成像的整合将发挥关键作用。为了复制临床前研究的临床放射治疗方法的复杂性，需要对小动物放射研究平台（SARRP）等系统进行重大技术进步，包括整合可靠的图像引导方法。US成像方法，包括多光谱光声断层扫描（MSOT），提供了相对于基于X射线、核医学（NM）和磁共振（MR）成像的现有方法改进和补充图像引导能力的潜力。研究我们的目标是（a）开发一个集成的SARP-MSOT图像引导的临床前RT设备和（B）使用它来帮助开发和优化新的成像方法和探针，以及新的治疗协同作用，以评估或增强辐射对癌细胞的影响。在五年的时间里，7个物理团队将在以下领域进行研究。将对SARRP进行修改，以便与MSOT共同注册，并在图像引导下使用临床上采用的最先进方法进行临床前肿瘤治疗。我们将开发用于精确确定应用辐射剂量的方法，并集成用于定量计算机断层扫描的特殊X射线检测器，该检测器能够区分组织类型并检测剂量增强纳米颗粒。我们将研究通过将US治疗与SARRP相结合来利用治疗协同作用的可能性。我们将修改MSOT设备用于US微泡成像，使用MSOT血液供应和氧合成像来优化RT和US治疗组合，研究使用US微泡来增强RT，并开发联合物理治疗的剂量参数。将开发和优化成像技术和探针化学，用于MSOT预测靶向放射增敏的增强，预后指示和肿瘤反应评估。性能将与NM探头和MR成像技术进行比较。将通过开发US图像与NM、MR和MSOT图像的配准来优化用于先进RT治疗的US引导方法，以预测放射敏感性，并开发和评估基于US的运动补偿剂量递送和成像，以随着治疗进展识别活肿瘤细胞的分布，以促进治疗适应性以避免复发。将通过向外部用户提供综合设施、举办讲习班以分享技术和科学信息以及规划、执行和报告联合研究，促进上述和其他领域的跨机构合作研究。

BACKGROUNDRadiotherapy (RT) is one of the most efficient tools in cancer treatment, and clinical RT is evolving considerably with technological advances in delivery and treatment planning. A key component of modern RT is enhanced image guidance, needed for precise tumour targeting, therapy monitoring and therapy assessment. To achieve the best care for patients with cancer receiving RT, developments are needed to optimise the physics and technology of image guidance. This should include the exploitation of new discoveries in targeted drugs and nanoparticles that increase tumour sensitivity to radiation, and of synergisms between RT and other physical therapies such as high intensity focused ultrasound (HIFU), hyperthermia and ultrasound (US) microbubble damage to tumour vasculature. These novel approaches to image guided RT must first be investigated in a preclinical setting before the most promising techniques can be translated to clinical studies. For this work, the integration of the best preclinical therapy with the best preclinical imaging will play a crucial role. To replicate the sophistication of clinical radiation treatment methods for preclinical research requires significant technological advances to systems such as the small animal radiation research platform (SARRP), including the integration of reliable methods for image guidance. US imaging methods, including multispectral optoacoustic tomography (MSOT), offer the potential for improved and complementary image guidance capability relative to existing methods based on x-ray, nuclear medicine (NM) and magnetic resonance (MR) imaging. RESEARCHWe aim to (a) develop an integrated SARRP-MSOT image guided preclinical RT facility and (b) use it to aid the development and optimisation of novel imaging methods and probes, and new therapeutic synergisms, to either evaluate or enhance effects of radiation on cancer cells. Over a five year period, 7 physics teams will conduct research in the following areas. The SARRP will be modified for co-registration with MSOT and for preclinical tumour treatment using the most advanced methods employed clinically, under image guidance. We will develop methods for accurate determination of applied radiation dose and integrate a special x-ray detector for quantitative computed tomography able to distinguish tissue types and detect dose-enhancing nanoparticles. We will investigate possibilities to exploit therapeutic synergisms by integrating US therapy with the SARRP. We will modify the MSOT device for US microbubble imaging, using MSOT imaging of blood supply and oxygenation to optimise RT and US treatment combinations, investigating the use of US microbubbles to enhance RT, and developing dose parameters for combined physical therapies.Imaging techniques and probe chemistry will be developed and optimised for MSOT prediction of enhancement of targeted radiosensitisation, indication of prognosis and assessment of tumour response. Performance will be compared with NM probes and MR imaging techniques. Methods for US guidance of advanced RT treatments will be optimised by developing co-registration of US images with NM, MR and MSOT images that predict radiosensitivity, and developing and evaluating US-based motion compensated dose delivery and imaging to identify the distribution of viable tumour cells as treatment progresses to facilitate treatment adaptation to avoid relapse.Finally, cross-institutional collaborative research in the above and other areas will be fostered by making the integrated facility available to external users and by running workshops for sharing technical and scientific information, and planning, executing and reporting on joint studies.