Integrating Quantitative Imaging and Biophysical Models to Predict Tumor Growth

描述(由申请人提供)：该项目的愿景是通过整合肿瘤生长的定量成像数据和生物物理模型来预测单个肿瘤对治疗的反应，从而开发出肿瘤预测方法。目前的肿瘤生长数学模型在实际应用中受到限制，因为它们需要输入数据，而在一个完整的生物体中，以任何合理的空间分辨率在 甚至是一个时间点，更不用说在多个时间点了。因此，此类模型在临床数据中的应用非常少，几乎没有纳入临床试验。将成像数据集成到肿瘤生长的数学模型中的动机是成像可以非侵入性地、在3D和多个时间点提供定量信息。可以在诊断时和治疗早期进行测量(而不干扰系统)，然后可以对这些数据进行建模，以预测治疗结束时的反应。通过这种方式，成像允许使用患者特定数据来初始化模型。我们相信，我们现在可以申请支持，进行一套完整的前瞻性研究，适当地设计来测试和验证两个基于成像的肿瘤生长和治疗反应的数学模型。为了实现这一目标，我们确定了以下两个具体目标：1.确定在治疗过程早期分别获得的动态增强MRI和扩散加权MRI测量肿瘤血管和细胞特征的能力，以初始化肿瘤生长的Logistic模型，以便预测个体动物的最终治疗反应。2.确定在治疗过程早期获得的肿瘤细胞、血管、缺氧和糖酵解特征的MRI和PET测量的能力，以初始化血管生成和细胞生长的生物物理模型，以便预测个体动物的最终治疗反应。这一系列研究的成功将有助于准确预测治疗效果，因此 无效的治疗方法可以转换为潜在的更有效的方法，从而使癌症患者能够实现实用的、具有临床相关性的个性化药物。

DESCRIPTION (provided by applicant): The vision of this program is to develop tumor forecasting methods by integrating quantitative imaging data and biophysical models of tumor growth to predict the response of individual tumors to therapy. Current mathematical models of tumor growth are limited in their practical applicability as they require input data that are extraordinarily difficult to obtain in an intact organism with any reasonable spatial resolution at even a single time point, let alone at multiple time points. Consequently, there has been very little application of such models to clinical data and virtually no incorporation into clinical trils. The motivation for integrating imaging data into mathematical models of tumor growth is that imaging can provide quantitative information noninvasively, in 3D, and at multiple time points. Measurements can be made (without disturbing the system) at the time of diagnosis and early in the course of treatment, and then these data can be modeled to predict response at the end of therapy. In this way, imaging allows models to be initialized with patient specific data. We believe we are now in the position to apply for support to perform a complete set of prospective studies appropriately designed for testing and validating two imaging based mathematical models of tumor growth and treatment response. To achieve this goal, we have identified the following two specific aims: 1. Determine the ability of dynamic contrast enhanced MRI and diffusion weighted MRI measurements of tumor vascular and cellular characteristics, respectively, obtained early in the course of therapy, to initialize the logistic model of tumor growth in order to predict final treatment response in individual animals. 2. Determine the abilit of MRI and PET measurements of tumor cellular, vascular, hypoxic, and glycolytic characteristics, obtained early in the course of therapy, to initialize a biophysical model of angiogenesis and cell growth in order to predict final treatment response in individual animals. Success in this line of investigation would allow for accurate prediction of treatment efficacy, so that ineffective therapies can be switched to potentially more effective approaches thereby enabling a practical, clinically relevant realization of personalized medicine for cancer patients.