MicroCT Imaging Based Theoretical Simulation and Protocol Design in Magnetic Nanoparticle Hyperthermia

CBET 1335958PI：朱清除原发部位的所有癌组织对于防止肿瘤复发或肿瘤转移至关重要。众所周知，一旦肿瘤转移到身体其他部位，治疗成本很高，治疗结果通常很差。在癌症治疗中，受到交变磁场影响的磁性纳米颗粒具有很高的细胞杀伤潜力，因为它可以将有限的热能传递给肿瘤，同时保护周围的健康组织。纳米粒子在肿瘤中的分布是决定肿瘤温度升高和治疗效果的主要因素。不幸的是，由于肿瘤的异质结构和复杂的过程，如颗粒沉积、聚集和摄取，颗粒扩散很难建模和控制。基于实际纳米颗粒沉积分布和肿瘤几何形状的肿瘤内温度场的理论模拟可以用于设计加热方案，真正实现个性化和最优的治疗计划。本研究项目的目标是利用MicroCT图像技术了解纳米颗粒在异质肿瘤中的传输，测试处理海量图像数据的计算能力，实施基于图像的设计方法来评估肿瘤的热损伤，并在现实的肿瘤模型中验证治疗方案。为了实现该项目的目标，将在理论和实验相结合的环境中开发创新任务，以测试基于microCT图像的计算方法是否成功地为移植到小鼠体内的前列腺癌设计最佳治疗方案。所设计的方案将通过加热过程中测量的肿瘤温度、肿瘤热损伤的组织学分析以及加热治疗后的肿瘤收缩监测来评估。该项目将为通过MicroCT成像了解肿瘤多孔结构和注射参数对纳米粒子在肿瘤中沉积的影响提供见解，并提高基于图像生成的肿瘤几何形状和粒子分布的理论模拟精度。人们认为，以前观察到的各种粒子沉积模式反映了不同的肿瘤孔道结构和注射参数对纳米粒子在注射过程中在肿瘤中扩散的影响。预计所获得的基础知识将导致肿瘤热损伤的最佳传递。可以预见，收集的纳米颗粒扩散模式的第一手定量成像也可以用于在未来的多尺度建模中检验假设和简化，提取传输特性，并最终提高对纳米颗粒在具有不同结构的肿瘤中的传输的理解。除了设计磁性纳米粒子热疗的治疗方案外，该项目的结果还可能扩展到其他应用，包括纳米毒理学和使用纳米载体的药物输送。

CBET 1335958PI: ZhuElimination all cancerous tissue at the original site is crucial to prevent recurring tumors or tumor metastasis. It is well known that cost of treatment is high and treatment outcomes are usually poor once tumor metastasizes to other parts of the body. Magnetic nanoparticles subject to an alternating magnetic field hold a high cell-killing potential in cancer treatment because it can deliver confined thermal energy to tumors, while preserving the surrounding healthy tissue. Nanoparticle distribution in tumors is a major factor in determining tumor temperature elevations and treatment efficacy. Unfortunately, particle spreading is difficult to model and control due to tumor heterogeneous structures and complex processes such as particle deposition, agglomeration, and intake. Theoretical simulation of temperature fields in tumors based on actual nanoparticle deposition distribution and tumor geometry can be used to design heating protocols to truly achieve individualized and optimal treatment planning. The objectives of this research project are to utilize microCT image technology to understand nanoparticle transport in heterogeneous tumors, to test computational capacity of handling vast data of images, to implement image-based design approaches in evaluating thermal damage in tumors, and to validate treatment protocols in realistic tumor models. To achieve the project's objectives, innovative tasks will be developed in a combined theoretical and experimental setting to test whether the microCT image-based computational approaches are successful in designing optimal treatment protocols for prostatic tumors implanted in mice. The designed protocols will be evaluated via measured tumor temperatures during heating, histological analyses of thermal damage in tumors, and tumor shrinkage monitoring after the heating treatment. This project will provide insights in understanding effects of tumor porous structures and injection parameters on nanoparticle deposition in tumors via microCT imaging, and to improve theoretical simulation accuracy based on image-generated tumor geometry and particle distribution. It is believed that the various particle deposition patterns observed previously reflect the effect of heterogeneous tumor porous structures and infusion parameters on nanoparticles spreading in tumors during injection. It is expected that the fundamental knowledge gained will result in optimal delivery of thermal damage in tumors. It is envisioned that the collected first-hand quantitative imaging of nanoparticle spreading patterns can also be used to test assumptions and simplifications in future multi-scale modeling, to extract transport properties, and to ultimately advance understanding of nanoparticle transport in tumors with heterogeneous structures. In addition to designing treatment protocols for magnetic nanoparticle hyperthermia, the results of the project may be extended to other applications including nanotoxicology and drug delivery using nano-carriers.