An Image Guided Small Animal Radiation Research Platform

描述（由申请人提供）：在过去的25年里，医学解剖成像取得了重大进展。最近，基于对体内和体外肿瘤细胞中各种分子和遗传信号的不断了解，人们对小动物生物成像研究的兴趣越来越大。具有讽刺意味的是，这些举措主要集中在药物和其他全身性药物的治疗研究上，而忽视了放射治疗。在放射治疗中加入生物成像信息将对治疗的管理和评估产生重大影响。不幸的是，尽管对生物成像研究感兴趣，动物辐射研究方法远远落后于临床实践。诸如适形调强放射治疗（IMRT）等先进技术正日益成为人类临床的常规疗法，并导致临床模式从均匀剂量递送向非均匀剂量递送的转变，特别是向关键器官。短期放射治疗的新图像引导方法的出现将导致剂量分布更大的不均匀性。遗憾的是，目前的实验室研究设备禁止在动物模型中测试这些范式。因此，先进的治疗技术在临床应用时，没有任何小动物辐射实验的指导，在临床前环境中评估疗效。在本申请中，我们申请资助一个图像引导小动物辐射研究平台（SARRP）的从头构建、测试和评估，该平台将准确地在小动物肿瘤模型系统、小鼠、大鼠和兔子中传递复杂的电离辐射剂量分布。具体而言，我们提出1)构建一个包含三个千伏辐射源的龙门系统，该系统的能量沉积分辨率约为1mm，机载锥束CT成像分辨率约为0.5 mm；2)发展剂量学和治疗计划方法，与人类治疗方法平行。最后(3)第三个具体目标是开发精确动物设置的方法，并验证该系统的成像和照射能力，以准确地在小动物中传递局部剂量分布。这项研究需要整合机械工程、x射线光学和辐射剂量学物理方面的专业知识。在生物工程研究伙伴关系（BRP）中，协作努力得到了最好的协调。成立了一个监督小组，以评估BRP的进展，并帮助确定未来研究的机会和假设。

DESCRIPTION (provided by applicant): Significant advances have been made in medical anatomical imaging over the past 25 years. More recently, there has been increased interest in small animal biological imaging research based on the increasing understanding of various molecular and genetic signals in tumor cells in vitro and in vivo. These initiatives have focused primarily on therapeutic research with drugs and other systemic agents, somewhat ironically, overlooking radiation therapy. The addition of biological imaging information to radiation therapy will have a major impact on the management and evaluation of treatment. Unfortunately, despite the interest in biological imaging research, animal radiation research methodology lags far behind clinical practices. Advanced techniques such as conformal, intensity modulated radiation therapy (IMRT) is increasingly becoming routine in human clinics, and has led to a shift in the clinical paradigm of the uniform dose delivery towards non-uniform dose delivery, particularly to the critical organs. The advent of new image guidance methods for short course radiation treatment will yet lead to the delivery of dose distributions of even greater nonuniformity. Regrettably, present laboratory research equipment prohibits testing of these paradigms in animal models. As a consequence, the advanced treatment technologies are applied clinically without any guidance from small animal radiation experimentation to evaluate efficacy in a preclinical setting. In this proposal we request funding for the de novo construction, testing and evaluation of an image guided small animal radiation research platform (SARRP) that will accurately deliver complex ionizing radiation dose distributions in small animal tumor model systems, mice, rats and rabbits. Specifically we propose 1) the construction of a gantry system containing three kilovoltage (kV) radiation sources that will have energy deposition resolution of about 1mm and on-board cone beam CT imaging resolution of about 0.5 mm; 2) the development of dosimetric and treatment planning methodologies that parallel that for human treatment. Finally (3) the third specific aim is to develop methods of precise animal setups and to validate the imaging and irradiation capabilities of the system for accurate delivery of localized dose distributions in small animals. The research requires integration of expertise in mechanical engineering, x-ray optics and radiation dosimetry physics. The collaborative efforts are best coordinated in a Bioengineering Research Partnership (BRP). An Oversight Group is formed to evaluate the progress of the BRP, and to help identify opportunities and hypotheses for future research.