Patient-specific predictive modeling that integrates advanced cancer imaging

描述（由申请人提供）：我们正在将肿瘤增殖和侵袭的数学建模与先进的癌症成像方法相结合。我们正在将这种方法应用于胶质瘤，这是一种侵袭性和高度侵袭性的原发性脑肿瘤，预后不佳。由于神经胶质瘤的组织相对难以接近，临床管理强烈依赖于影像学，因此迫切需要将影像学变化与对癌症系统的动态理解相结合的工具。我们项目的目标是双重的：通过治疗胶质瘤来影响当前的临床挑战，并为开发针对这些具有挑战性的癌症的新疗法提供工具。我们的第一个目标是根据每个患者肿瘤的生长动力学，如解剖成像（MR）和功能成像（PET和晚期MR）所见，开发基于图像的反应指标。我们将使用数学建模来开发一个患者特异性的未经治疗的虚拟成像控制（UVIC），量化每个患者肿瘤系统的动态。然后，我们将针对20名胶质母细胞瘤患者在多个时间点（平均5个时间点）对一组新的配对PET和MR图像进行UVIC模型测试。配对图像将在整个治疗过程中获得，并与UVIC预测的缺氧（FMISO-PET）、坏死（T1-Gd MR）和细胞结构（DWI MR）图像进行比较。该项目的第二个总体目标是将UVIC模型扩展到临床试验中个体患者的早期反应评估。这将为开发对胶质瘤更有效的急需的治疗方法提供工具。该项目开发的方法可以通过改进生物模型加以扩展，也可以通过使用适当的生长动力学模型应用于其他癌症。

DESCRIPTION (provided by applicant): We are integrating the mathematical modeling of tumor proliferation and invasion with advanced cancer imaging methods. We are applying this approach to gliomas, which are aggressive and highly invasive primary brain tumors associated with dismal prognoses. Because of the relative inaccessibility of tissue, the clinical management of gliomas are strongly directed by imaging, thus tools integrating changes on imaging with a dynamic understanding of the cancer system are sorely needed. The goals of our project are twofold: To impact current clinical challenges with treatment of gliomas, and to provide tools for the development of new therapies for these challenging cancers. Our first goal is to develop image-based response metrics based on the growth kinetics of each patient's tumor, as seen on both anatomical imaging (MR) and functional imaging (PET and advanced MR). We will use mathematical modeling to develop a patient-specific Untreated Virtual Imaging Control (UVIC) that quantifies the dynamics of each patient's tumor system. We will then test the UVIC model against a novel set of paired PET and MR images at multiple time-points (five on average) for each of 20 glioblastoma patients. The paired images will be acquired throughout the course of therapy and compared with the UVIC predicted images of hypoxia (FMISO-PET), necrosis (T1-Gd MR) and cellularity (DWI MR). The second, and overall, goal of this project is to extend the UVIC model to the early response assessment of individual patients in clinical trials. This will provide a tool for the development of much-needed therapies that are more effective for gliomas. The methodologies developed in the project could be extended by refining the biological modeling, and could also be applied to other cancers by the use of appropriate growth kinetic models.