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

背景放射治疗(RT)是治疗癌症最有效的手段之一，随着治疗方法和治疗计划技术的进步，临床放射治疗也在不断发展。现代放射治疗的一个关键组成部分是增强的图像引导，这是精确的肿瘤靶向、治疗监测和治疗评估所必需的。为了实现对接受放射治疗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来提高肿瘤对辐射的敏感性，以及RT与其他物理治疗之间的协同作用，例如高强度聚焦超声(HIFU)、热疗和超声(US)微泡对肿瘤血管的损害。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，然后最有希望的技术才能转化为临床研究。对于这项工作，最好的临床前治疗与最好的临床前成像的整合将发挥关键作用。要将复杂的临床放射治疗方法复制到临床前研究中，需要对小动物辐射研究平台(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。美国的成像方法，包括多光谱光声成像(MSOT)，相对于基于X射线、核医学(NM)和磁共振(MR)成像的现有方法，提供了改进和补充图像制导能力的潜力。研究我们的目标是(A)开发一个集成的SARRP-MSOT图像引导的临床前放射治疗设备，并(B)利用它来帮助开发和优化新的成像方法和探针，以及新的治疗协同效应，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将进行修改，以便与MSOT共同注册，并在图像指导下使用临床上使用的最先进方法进行临床前肿瘤治疗。我们将开发准确确定所用辐射剂量的方法，并集成一种用于定量计算机断层扫描的特殊X射线探测器，该探测器能够区分组织类型并检测剂量增强纳米颗粒。我们将研究通过将US疗法与SARRP相结合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，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，并开发用于综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预测靶向放射敏感性的增强、预后的指示和肿瘤反应的评估。性能将与NM探头和磁共振成像技术进行比较。通过开发US图像与预测辐射敏感性的NM、MR和MSOT图像的共同配准，开发和评估基于美国的运动补偿剂量传递和成像以识别在治疗过程中存活的肿瘤细胞的分布，以促进治疗适应以避免复发，将优化US指导先进RT治疗的方法。最后，通过向外部用户提供综合设施以及举办研讨会以共享技术和科学信息，以及规划、执行和报告联合研究，将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.