Image-Guided Magnetic Nanoparticle Hyperthermia

Arepally, Nageshwar

Image-Guided Magnetic Nanoparticle Hyperthermia

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Author:: Arepally, Nageshwar
Graduate Program:: Mechanical Engineering
Degree:: Master of Science
Document Type:: Master Thesis
Date of Defense:: October 16, 2023
Committee Members:: Anilchandra Attaluri, Thesis Advisor/Co-Advisor
Ma'Moun Abdel Abu-Ayyad, Committee Member
Rick Ciocci, Professor in Charge/Director of Graduate Studies
Brian Allen Maicke, Committee Member
Hayden Carlton, Committee Member
Keywords:: MNPH
MPI
AMF
MION
FE-BHT
PID
resolution
Abstract:: Magnetic Nanoparticle Hyperthermia (MNPH) is a thermal therapy modality used to improve the effectiveness of chemotherapy and radiation therapy in the treatment of locally advanced solid tumors. MNPH involves the injection of magnetic iron nanoparticles (MIONs) into the tumor, followed by the application of an alternating magnetic field (AMF) to generate heat from MIONs. During MNPH, the tumor temperature should be maintained above 43 [°C] for 20-60 [min] while maintaining the surrounding healthy tissue below 39 [°C]. Information on the intratumor distribution of MION is critical for planning MNPH treatment. Magnetic Particle Imaging (MPI) can determine the intratumor distribution of MION with millimeter spatial resolution. This study explored the feasibility of MPI-informed prediction of MNPH temperature and compared it with the current practice of modeling the MION distribution as a concentrated heat source at the injection site. A simplified geometry of the subcutaneous mice tumor model was developed to perform finite element (FE) bio-heat transfer (BHT) analysis. FE-BHT model with MPI-informed total MION concentration and MION volume overestimated the average change in tumor temperature by 1 [°C] to 4 [°C] compared to experimentally measured tumor temperature data. The impact of MPI resolution on intratumor temperature predictions was explored using the FE-BHT model. A theoretical sensitivity analysis was conducted to identify the minimum MPI spatial resolution required for FE-BHT to predict temperatures within 1 °C of the highest possible MPI resolution of 0.15 [mm]. MPI spatial resolutions of 0.3 [mm] to 0.5 [mm], predicted temperatures within 1 [°C] of the highest possible MPI resolution. A feedback control system is crucial for delivering a precise thermal dose (TD) to the tumor while minimizing damage to adjacent healthy tissues. A proportional-integral-derivative (PID) controller was designed using the FE-BHT model. An additional constraint of a maximum allowable tumor temperature of 60 [°C] was imposed to avoid large thermal gradients. The simulated PID controller utilized feedback from deposited thermal dose and temperature at the tumor boundary. The target thermal dose (CEM43T10) was achieved within 11 min, while maintaining the tumor boundary (Tb) at 43 [°C]. This study demonstrated the feasibility of using an MPI-informed FE-BHT in a preclinical scenario; however, further verification and validation of the models are necessary. Lower MPI resolutions of 0.3 [mm] to 0.5 [mm] underestimate the predicted temperatures within 1 [°C]. However, this reduction in resolution can significantly reduce the imaging time and computational resources required for the FE-BHT model, thereby making real-time treatment planning more feasible in the future. Although the designed PID controller performed well in some scenarios, it was unstable in others. In future work, exploring the use of a model predictive controller (MPC) may be beneficial.

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