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，随着技术的进步和治疗计划的发展，临床放疗也在不断发展。现代放射治疗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。为了给接受放射治疗的癌症患者提供最好的护理，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）、热疗和超声（US）对肿瘤血管的微泡损伤）之间的协同作用。这些图像引导RT的新方法必须首先在临床前环境中进行研究，然后才能将最有希望的技术转化为临床研究。在这项工作中，将最佳临床前治疗与最佳临床前成像相结合将发挥至关重要的作用。为了在临床前研究中复制临床放射治疗方法的复杂性，需要对小动物辐射研究平台（SARRP）等系统进行重大的技术进步，包括整合可靠的图像引导方法。与基于x射线、核医学（NM）和磁共振（MR）成像的现有方法相比，包括多光谱光声断层扫描（MSOT）在内的美国成像方法，提供了改进和补充图像引导能力的潜力。我们的目标是(a)开发一个集成的SARRP-MSOT图像引导临床前RT设备，(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。SARRP将被修改为与MSOT共同注册，并在图像指导下使用临床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测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射线探测器，能够区分组织类型并检测剂量增强纳米颗粒。我们将研究通过整合美国治疗与SARRP来开发治疗协同效应的可能性。我们将改进用于US微泡成像的MSOT设备，利用MSOT血供和氧合成像优化RT和US治疗组合，研究US微泡增强RT的使用，并制定联合物理治疗的剂量参数。成像技术和探针化学将被开发和优化，用于MSOT预测靶向放射增敏的增强，预后指示和肿瘤反应的评估。性能将与纳米探针和磁共振成像技术进行比较。通过开发超声图像与NM、MR和MSOT图像的联合配准，预测放射敏感性，以及开发和评估基于运动补偿的剂量传递和成像，以确定治疗进展中活肿瘤细胞的分布，以促进治疗适应，避免复发，将优化超声指导高级放疗治疗的方法。最后，将通过向外部用户提供综合设施和举办讲习班分享技术和科学资料以及规划、执行和报告联合研究来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.