Small Animal Image-Guided Radiotherapy

描述(由申请人提供)：本提案的目标是实施和评估基于微型CT扫描仪的小动物图像引导放射治疗(IGRT)的全功能解决方案。目前，用于照射疾病动物模型的方法与临床上常规使用的方法几乎没有相似之处。通过开发接近临床程序能力的小动物放射治疗技术，我们将能够调查与临床医学和分子生物学相关的各种研究问题。我的实验室的初步研究证明了基于实验室的适形放射治疗的可行性，在该实验室中，在商业上可用的MicroCT系统中添加了可变孔径准直器，产生了一个能够向小动物对象提供具有任意大小的圆形轮廓的径向会聚X射线束的系统。在这个项目中，我们将应用这项新技术来创建、评估和初步应用一种综合的方法，用于对小动物进行成像、治疗计划和放射治疗。由于该系统将作为商业MicroCT扫描仪的硬件和软件扩展而开发，因此它具有以低成本在世界各地的多个中心应用于生物医学研究的潜力。在该系统生成后，我们将把它应用于原位癌症模型治疗中的放射治疗研究，允许在实验室环境中评估新出现的治疗范例。这些努力将建立一种在实验室探索放射治疗和放射生物学的新机制，并将为设计临床试验使用的新治疗方案的优点提供直接证据。在这项研究中，将开发一种用于治疗小动物的系统，该系统采用临床相似的图像引导适形放射治疗。该设备基于商业上可获得的MicroCT扫描仪，具有在科学界广泛传播和使用的潜力，并将使实验室能够研究与临床相关的新型放射疗法和放射生物学。这一研究主题将在本项目中通过应用该系统来研究低分割和超分割方案以及低氧图像引导放射治疗，为后续的临床翻译提供数据。

DESCRIPTION (provided by applicant): The goal of this proposal is to implement and evaluate a full-featured solution for image-guided radiotherapy (IGRT) of small animals based on a microCT scanner. At present, the methods used to irradiate animal models of disease bear little resemblance to those routinely applied in the clinic. Through the development of radiotherapy techniques for small animals that approach the capabilities of clinical procedures, we will enable investigation of a variety of research questions relevant to clinical medicine as well as molecular biology. The feasibility of laboratory-based conformal radiotherapy has been demonstrated by preliminary investigations in my laboratory in which a variable aperture collimator has been added to a commercially available microCT system, generating a system capable of delivering radially convergent X-ray beams with circular profiles of arbitrary sizes to small animal subjects. In this project we will apply this novel technology towards the creation, evaluation, and preliminary application of a comprehensive method for imaging, treatment planning, and radiation delivery to small animals. Because this system will be developed as a hardware and software expansion for a commercial microCT scanner, it has the potential to be applied in biomedical research at a number of centers throughout the world at low cost. After generation of the system we will apply it in the study of radiotherapy in the treatment of orthotopic models of cancer, allowing evaluation of emerging therapeutic paradigms in a laboratory environment. These efforts will establish a new mechanism for exploring radiotherapy and radiobiology in the laboratory and will provide direct evidence of the merit of novel treatment regimens for use in designing clinical trials. In this research a system for treating small animals with clinically-similar image-guided conformal radiotherapy will be developed. The device, based on a commercially available microCT scanner, has the potential for widespread distribution and use within the scientific community, and will enable research of novel clinically- relevant radiation therapies and radiobiology in a laboratory. This research theme will be explored in this project by applying the system towards studying hypo- and hyper-fractionation schemes as well as hypoxia image-guided radiotherapy, providing data for subsequent clinical translation.