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

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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.