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Temperature-controlled power modulation compensates for heterogeneous nanoparticle distributions: a computational optimization analysis for magnetic hyperthermia
Authors:Sri Kamal Kandala  Eleni Liapi  Louis L Whitcomb  Anilchandra Attaluri
Institution:1. Department of Mechanical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA;2. Department of Radiation Oncology and Molecular Radiation Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA;3. Department of Radiology and Radiological Sciences, Johns Hopkins Hospital, Baltimore, MD, USA;4. Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA;5. Department of Oncology, School of Medicine, Johns Hopkins University Baltimore, MD, USA;6. Department of Mechanical Engineering, The Pennsylvania State University – Harrisburg, Middletown, PA, USA
Abstract:Purpose: To study, with computational models, the utility of power modulation to reduce tissue temperature heterogeneity for variable nanoparticle distributions in magnetic nanoparticle hyperthermia.

Methods: Tumour and surrounding tissue were modeled by elliptical two- and three-dimensional computational phantoms having six different nanoparticle distributions. Nanoparticles were modeled as point heat sources having amplitude-dependent loss power. The total number of nanoparticles was fixed, and their spatial distribution and heat output were varied. Heat transfer was computed by solving the Pennes’ bioheat equation using finite element methods (FEM) with temperature-dependent blood perfusion. Local temperature was regulated using a proportional-integral-derivative (PID) controller. Tissue temperature, thermal dose and tissue damage were calculated. The required minimum thermal dose delivered to the tumor was kept constant, and heating power was adjusted for comparison of both the heating methods.

Results: Modulated power heating produced lower and more homogeneous temperature distributions than did constant power heating for all studied nanoparticle distributions. For a concentrated nanoparticle distribution, located off-center within the tumor, the maximum temperatures inside the tumor were 16% lower for modulated power heating when compared to constant power heating. This resulted in less damage to surrounding normal tissue. Modulated power heating reached target thermal doses up to nine-fold more rapidly when compared to constant power heating.

Conclusions: Controlling the temperature at the tumor-healthy tissue boundary by modulating the heating power of magnetic nanoparticles demonstrably compensates for a variable nanoparticle distribution to deliver effective treatment.

Keywords:Hyperthermia  magnetic nanoparticles  thermal dose  Pennes bioheat equation  perfusion modeling  bioheat transfer
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