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

在原发部位清除所有癌变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，治疗费用高，治疗效果通常很差。受交变磁场影响的磁性纳米颗粒在癌症治疗中具有很高的细胞杀伤潜力，因为它可以向肿瘤提供有限的热能，同时保留周围的健康组织。纳米颗粒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，由于肿瘤的非均匀结构和复杂的过程，如颗粒沉积、团聚和摄入，颗粒的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对肿瘤内温度场进行理论模拟，设计加热方案，真正实现个体化和最优治疗方案。本研究项目的目标是利用微ct图像技术来了解纳米颗粒在异质肿瘤中的传输，测试处理大量图像数据的计算能力，实现基于图像的设计方法来评估肿瘤的热损伤，并在现实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，以测试基于微ct图像的计算方法是否成功地为植入小鼠的前列腺肿瘤设计最佳治疗方案。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和加热处理后的肿瘤收缩监测来评估。该项目将通过微ct成像了解肿瘤多孔结构和注射参数对肿瘤中纳米颗粒沉积的影响，并提高基于图像生成的肿瘤几何形状和颗粒分布的理论模拟精度。我们认为，之前观察到的各种颗粒沉积模式反映了注射过程中肿瘤异质性多孔结构和注射参数对纳米颗粒在肿瘤中扩散的影响。预计所获得的基本知识将导致肿瘤中热损伤的最佳递送。预计收集到的纳米颗粒扩散模式的第一手定量成像也可用于测试未来多尺度建模中的假设和简化，提取运输特性，并最终推进对具有异质结构的肿瘤中纳米颗粒运输的理解。除了设计磁性纳米粒子热疗的治疗方案外，该项目的结果可能会扩展到其他应用，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.