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      Validation of a coupled electromagnetic and thermal model for estimating temperatures during magnetic nanoparticle hyperthermia

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          Abstract

          Purpose:

          Alternating magnetic field (AMF) tissue interaction models are generally not validated. Our aim was to develop and validate a coupled electromagnetic and thermal model for estimating temperatures in large organs during magnetic nanoparticle hyperthermia (MNH).

          Materials and methods:

          Coupled finite element electromagnetic and thermal model validation was performed by comparing the results to experimental data obtained from temperatures measured in homogeneous agar gel phantoms exposed to an AMF at fixed frequency (155 ± 10 kHz). The validated model was applied to a three-dimensional (3D) rabbit liver built from computed tomography (CT) images to investigate the contribution of nanoparticle heating and nonspecific eddy current heating as a function of AMF amplitude.

          Results:

          Computed temperatures from the model were in excellent agreement with temperatures calculated using the analytical method (error < 1%) and temperatures measured in phantoms (maximum absolute error <2% at each probe location). The 3D rabbit liver model for a fixed concentration of 5mg Fe/cm 3 of tumor revealed a maximum temperature ~44 °C in tumor and ~40 °C in liver at AMF amplitude of ~12 kA/m (peak).

          Conclusion:

          A validated coupled electromagnetic and thermal model was developed to estimate temperatures due to eddy current heating in homogeneous tissue phantoms. The validated model was successfully used to analyze temperature distribution in complex rabbit liver tumor geometry during MNH. In future, model validation should be extended to heterogeneous tissue phantoms, and include heat sink effects from major blood vessels.

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          Most cited references74

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          Analysis of tissue and arterial blood temperatures in the resting human forearm.

          H H PENNES (1948)
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            Exchange-coupled magnetic nanoparticles for efficient heat induction.

            The conversion of electromagnetic energy into heat by nanoparticles has the potential to be a powerful, non-invasive technique for biotechnology applications such as drug release, disease treatment and remote control of single cell functions, but poor conversion efficiencies have hindered practical applications so far. In this Letter, we demonstrate a significant increase in the efficiency of magnetic thermal induction by nanoparticles. We take advantage of the exchange coupling between a magnetically hard core and magnetically soft shell to tune the magnetic properties of the nanoparticle and maximize the specific loss power, which is a gauge of the conversion efficiency. The optimized core-shell magnetic nanoparticles have specific loss power values that are an order of magnitude larger than conventional iron-oxide nanoparticles. We also perform an antitumour study in mice, and find that the therapeutic efficacy of these nanoparticles is superior to that of a common anticancer drug.
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              Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme

              Therapy options at the time of recurrence of glioblastoma multiforme are often limited. We investigated whether treatment with a new intratumoral thermotherapy procedure using magnetic nanoparticles improves survival outcome. In a single-arm study in two centers, 66 patients (59 with recurrent glioblastoma) received neuronavigationally controlled intratumoral instillation of an aqueous dispersion of iron-oxide (magnetite) nanoparticles and subsequent heating of the particles in an alternating magnetic field. Treatment was combined with fractionated stereotactic radiotherapy. A median dose of 30 Gy using a fractionation of 5 × 2 Gy/week was applied. The primary study endpoint was overall survival following diagnosis of first tumor recurrence (OS-2), while the secondary endpoint was overall survival after primary tumor diagnosis (OS-1). Survival times were calculated using the Kaplan–Meier method. Analyses were by intention to treat. The median overall survival from diagnosis of the first tumor recurrence among the 59 patients with recurrent glioblastoma was 13.4 months (95% CI: 10.6–16.2 months). Median OS-1 was 23.2 months while the median time interval between primary diagnosis and first tumor recurrence was 8.0 months. Only tumor volume at study entry was significantly correlated with ensuing survival (P < 0.01). No other variables predicting longer survival could be determined. The side effects of the new therapeutic approach were moderate, and no serious complications were observed. Thermotherapy using magnetic nanoparticles in conjunction with a reduced radiation dose is safe and effective and leads to longer OS-2 compared to conventional therapies in the treatment of recurrent glioblastoma.
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                Author and article information

                Journal
                8508395
                4857
                Int J Hyperthermia
                Int J Hyperthermia
                International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group
                0265-6736
                1464-5157
                23 July 2021
                2021
                13 August 2021
                : 38
                : 1
                : 611-622
                Affiliations
                [a ]Department of Mechanical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA
                [b ]Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
                [c ]Department of Radiology and Radiological Sciences, Johns Hopkins Hospital, Baltimore, MD, USA
                [d ]Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA
                [e ]Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
                [f ]Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA
                [g ]Department of Mechanical Engineering, The Pennsylvania State University - Harrisburg, Middletown, PA, USA
                Author notes
                CONTACT Anilchandra Attaluri aua473@ 123456psu.edu Department of Mechanical Engineering, School of Science, Engineering, and Technology, The Pennsylvania State University – Harrisburg, Olmsted Building, Room W-231C, 777 W. Harrisburg Pike, Middletown 17057, PA, USA
                Article
                NIHMS1727278
                10.1080/02656736.2021.1913244
                8363028
                33853493
                5d32f687-4892-4329-8604-dbfebf10bcb9

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Categories
                Article

                Medicine
                hyperthermia,magnetic nanoparticles,eddy currents,electromagnetic modeling,bioheat transfer,gel phantom,verification and validation

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