Quantitative evaluation of effects of coupled temperature elevation, thermal damage, and enlarged porosity on nanoparticle migration in tumors during magnetic nanoparticle hyperthermia

2021 ◽  
Vol 126 ◽  
pp. 105393
Author(s):  
Manpreet Singh ◽  
Ronghui Ma ◽  
Liang Zhu
Keyword(s):  
Quantitative Evaluation ◽  
Magnetic Nanoparticle ◽  
Thermal Damage ◽  
Temperature Elevation ◽  
Magnetic Nanoparticle Hyperthermia

scholarly journals Heating Protocol Design Affected by Nanoparticle Redistribution and Thermal Damage Model in Magnetic Nanoparticle Hyperthermia for Cancer Treatment

2020 ◽  
Vol 142 (7) ◽  
Author(s):  
Manpreet Singh ◽  
Qimei Gu ◽  
Ronghui Ma ◽  
Liang Zhu
Keyword(s):  
Magnetic Nanoparticle ◽  
Thermal Damage ◽  
Damage Model ◽  
Heating Time ◽  
Control Group ◽  
Temperature Elevation ◽  
Theoretical Simulation ◽  
Nanoparticle Distribution ◽  
Magnetic Nanoparticle Hyperthermia ◽  
Experimental Group

Abstract Recent micro-CT scans have demonstrated a much larger magnetic nanoparticle distribution volume in tumors after localized heating than those without heating, suggesting possible heating-induced nanoparticle migration. In this study, a theoretical simulation was performed on tumors injected with magnetic nanoparticles to evaluate the extent to which the nanoparticle redistribution affects the temperature elevation and thermal dosage required to cause permanent thermal damage to PC3 tumors. 0.1 cc of a commercially available ferrofluid containing magnetic nanoparticles was injected directly to the center of PC3 tumors. The control group consisted of four PC3 tumors resected after the intratumoral injection, while the experimental group consisted of another four PC3 tumors injected with ferrofluid and resected after 25 min of local heating. The micro-CT scan generated tumor model was attached to a mouse body model. The blood perfusion rates in the mouse body and PC3 tumor were first extracted based on the experimental data of average mouse surface temperatures using an infrared camera. A previously determined relationship between nanoparticle concentration and nanoparticle-induced volumetric heat generation rate was implemented into the theoretical simulation. Simulation results showed that the average steady-state temperature elevation in the tumors of the control group is higher than that in the experimental group where the nanoparticles are more spreading from the tumor center to the tumor periphery (control group: 70.6±4.7 °C versus experimental group: 69.2±2.6 °C). Further, we assessed heating time needed to cause permanent thermal damage to the entire tumor, based on the nanoparticle distribution in each tumor. The more spreading of nanoparticles to tumor periphery in the experimental group resulted in a much longer heating time than that in the control group. The modified thermal damage model by Dr. John Pearce led to almost the same temperature elevation distribution; however, the required heating time was at least 24% shorter than that using the traditional Arrhenius integral, despite the initial time delay. The results from this study suggest that in future simulation, the heating time needed when considering dynamic nanoparticle migration during heating is probably between 19 and 29 min based on the Pearce model. In conclusion, the study demonstrates the importance of including dynamic nanoparticle spreading during heating and accurate thermal damage model into theoretical simulation of temperature elevations in tumors to determine thermal dosage needed in magnetic nanoparticle hyperthermia design.

Nanoparticle Redistribution During Magnetic Nanoparticle Hyperthermia: Multi-Physics Porous Medium Model Analyses

2012 ◽  
Author(s):  
Anilchandra Attaluri ◽  
Robert Ivkov ◽  
Ronghui Ma ◽  
Liang Zhu
Keyword(s):  
Heat Transfer ◽  
Porous Media ◽  
Magnetic Nanoparticle ◽  
Thermal Damage ◽  
Heat Transfer Model ◽  
Transfer Model ◽  
Model Based ◽  
Porous Media Model ◽  
Magnetic Nanoparticle Hyperthermia ◽  
And Diffusion

A coupled theoretical framework comprising a suspension of nanoparticles transport in porous media model and a heat transfer model is developed to address nanoparticle redistribution during heating. Nanoparticle redistribution in biological tissues during magnetic nanoparticle hyperthermia is described by a multi-physics model that consists of five major components: (a) a fully saturated porous media model for fluid flow through tissue; (b) nanoparticle convection and diffusion; (c) heat transfer model based on heat generation by local nanoparticle concentration; (d) a model to predict tissue thermal damage and corresponding change to the porous structure; and (e) a nanoparticle redistribution model based on the dynamic porosity and diffusion diffusivity. The integrated model has been used to predict the structural damage in porous tumors and its effect on nanoparticle-induced heating in tumors. Thermal damage in the vicinity of the tumor center that is predicted by the Arrhenius equation increases from 14% with 10 minutes of heating to almost 99% after 20 minutes. It then induces an increased tumor porosity that increases nanoparticle diffusivity by seven-fold. The model predicts thermal damage induced by nanoparticle redistribution increases by 20% in the radius of the spherical tissue region containing nanoparticles. The developed model has demonstrated the feasibility of enhancing nanoparticle dispersion from injection sites using targeted thermal damage.

Numerical Study of Nanofluid Transport in Tumors During Nanofluid Infusion for Magnetic Nanoparticle Hyperthermia Treatment

2012 ◽  
Author(s):  
Di Su ◽  
Ronghui Ma ◽  
Liang Zhu
Keyword(s):  
Magnetic Nanoparticle ◽  
Numerical Study ◽  
Critical Role ◽  
Oxide Nanoparticles ◽  
Temperature Elevation ◽  
Hyperthermia Treatment ◽  
Nanoparticle Distribution ◽  
Lack Of Control ◽  
Magnetic Nanoparticle Hyperthermia ◽  
Transport In Tumors

The application of nanostructures in hyperthermia treatment of cancer has attracted growing research interest due to the fact that magnetic nanoparticles are able to generate impressive levels of heat when excited by an external magnetic field [1–3]. Various types of nanoparticles such as magnetite and superparamagentic iron oxide nanoparticles have demonstrated great potentials in hyperthermia treatment; however many challenges need to be addressed for future applications of this method in clinical studies. One leading issue is the limited knowledge of nanoparticle distribution in tumors. Since the temperature elevation is induced as the result of the heat generation by the nanoparticles, the concentration distributions of the particles in a tumor play a critical role in determining the efficacy of the treatment. The lack of control of the nanoparticle distribution may lead to inadequacy in killing tumor cells and/or damage to the healthy tissue.

Tumor Geometry and SAR Distribution Generated From MicroCT Images for Tumor Temperature Elevation Simulation in Magnetic Nanoparticle Hyperthermia

2013 ◽  
Author(s):  
Alexander LeBrun ◽  
Navid Manuchehrabadi ◽  
Anilchandra Attaluri ◽  
Ronghui Ma ◽  
Liang Zhu
Keyword(s):  
Numerical Simulation ◽  
Magnetic Nanoparticles ◽  
Temperature Distribution ◽  
Magnetic Nanoparticle ◽  
Heat Transfer Process ◽  
Simulation Software ◽  
Temperature Elevation ◽  
Hyperthermia Treatment ◽  
Software Packages ◽  
Magnetic Nanoparticle Hyperthermia

Previous investigations in magnetic nanoparticle hyperthermia for cancer treatments have demonstrated that particle size, particle coating, and magnetic field strength and frequency determine its heating generation capacity. However, once the nanoparticles are manufactured, the spatial distribution of the nanostructures dispersed in tissue dominates the spatial temperature elevation during heating. 1–3 Therefore, understanding the distribution of magnetic nanoparticles in tumors is critical to develop theoretical models to predict temperature distribution in tumors during hyperthermia treatment. An accurate description of the nanoparticle distribution and the tumor geometry will greatly enhance the simulation accuracy of the heat transfer process in tumors, which is crucial for generating an optimal temperature distribution that can prevent the occurrence of heating under-dosage in the tumor and overheating in the healthy tissue. Recently studies by our group have demonstrated that the nanoparticle concentration distribution in tumors can be visualized via microCT image due to the density elevation of the presence of magnetic nanoparticles. 4 The problem is the intensive memory requirements to directly import the microCT images to numerical simulation software packages such as COMSOL. Although commercial software packages exist to handle detailed entities inside tumors, they are very expensive to purchase. In addition, having very small entities at the micrometer level inside the tumor geometry may provide challenge to numerical simulation software to accept the generated geometry.

Treatment Efficacy for Validating MicroCT-Based Theoretical Simulation Approach in Magnetic Nanoparticle Hyperthermia for Cancer Treatment

2017 ◽  
Vol 139 (5) ◽  
Author(s):  
Alexander LeBrun ◽  
Tejashree Joglekar ◽  
Charles Bieberich ◽  
Ronghui Ma ◽  
Liang Zhu
Keyword(s):  
Treatment Efficacy ◽  
Magnetic Nanoparticle ◽  
Thermal Damage ◽  
Theoretical Models ◽  
Control Group ◽  
Tumor Shrinkage ◽  
Tumor Cell Death ◽  
Theoretical Simulation ◽  
Magnetic Nanoparticle Hyperthermia

The objective is to validate a designed heating protocol in a previous study based on treatment efficacy of magnetic nanoparticle hyperthermia in prostate tumors. In vivo experiments have been performed to induce temperature elevations in implanted PC3 tumors injected with magnetic nanoparticles, following the same heating protocol designed in our previous microCT-based theoretical simulation. A tumor shrinkage study and histological analyses of tumor cell death are conducted after the heating. Tumor shrinkage is observed over a long period of 8 weeks. Histological analyses of the tumors after heating are used to evaluate whether irreversible thermal damage occurs in the entire tumor region. It has been shown that the designed 25 min heating (Arrhenius integral Ω ≥ 4 in the entire tumor) on tumor tissue is effective to cause irreversible thermal damage to PC3 tumors, while reducing the heating time to 12 min (Ω ≥ 1 in the entire tumor) results in an initial shrinkage, however, later tumor recurrence. The treated tumors with 25 min of heating disappear after only a few days. On the other hand, the tumors in the control group without heating show approximately an increase of more than 700% in volume over the 8-week observation period. In the undertreated group with 12 min of heating, its growth rate is smaller than that in the control group. In addition, results of the histological analysis suggest vast regions of apoptotic and necrotic cells, consistent with the regions of significant temperature elevations. In conclusion, this study demonstrates the importance of imaging-based design for individualized treatment planning. The success of the designed heating protocol for completely damaging PC3 tumors validates the theoretical models used in planning heating treatment in magnetic nanoparticle hyperthermia.

Temperature Distribution and Thermal Dosage Affected by Nanoparticle Distribution in Tumours During Magnetic Nanoparticle Hyperthermia

2019 ◽  
Author(s):  
Manpreet Singh ◽  
Qimei Gu ◽  
Ronghui Ma ◽  
Liang Zhu
Keyword(s):  
Magnetic Nanoparticle ◽  
Thermal Damage ◽  
Local Heating ◽  
Heating Time ◽  
Control Group ◽  
Theoretical Simulation ◽  
Nanoparticle Distribution ◽  
Tumor Periphery ◽  
Magnetic Nanoparticle Hyperthermia ◽  
Experimental Group

Abstract Recent microCT imaging study has demonstrated that local heating caused a much larger nanoparticle distribution volume in tumors than that in tumors without localized heating, suggesting possible nanoparticle redistribution/migration during heating. In this study, a theoretical simulation is performed to evaluate to what extent the nanoparticle redistribution affects the temperature elevations and thermal dosage required to cause permanent thermal damage to PC3 tumors. Two tumor groups with similar sizes are selected. The control group consists of five PC3 tumors with nanoparticles distribution without heating, while the experimental group consists of another five resected PC3 tumors with nanoparticles distribution obtained after 25 minutes of local heating. Each generated tumor model is attached to a mouse body model by microCT scans. A previously determined relationship between the nanoparticle concentration distribution and the volumetric heat generation rate is implemented in the theoretical simulation of temperature elevations during magnetic nanoparticle hyperthermia. Our simulation results show that the average steady state temperature elevation in the tumors of the control group is higher than that in the experimental group when the nanoparticles are more spreading from the tumor center to tumor periphery (control group: 64.03±3.2°C vs. experimental group: 62.04±3.07°C). Further we assess the thermal dosage needed to cause 100% permanent thermal damage (Arrhenius integral Ω = 4) to the entire tumor, based on the assumption of unchanged nanoparticle distribution during heating. The average heating time based on the experimental setting from our previous studies demonstrates significantly different designs. Specifically, the average heating time for the control group is 24.3 minutes. However, the more spreading of nanoparticles to tumor periphery in the experimental group results in a much longer heating time of 38.1 minutes, 57° longer than that in the control group, to induce permanent thermal damage to the entire tumor. The results from this study suggest that the heating time needed when considering dynamic nanoparticle migration during heating is probably between 24 to 38 minutes. In conclusion, the study demonstrates the importance of including dynamic nanoparticle spreading during heating into theoretical simulation of temperature elevations in tumors to determine accurate thermal dosage needed in magnetic nanoparticle hyperthermia design.

MicroCT image-generated tumour geometry and SAR distribution for tumour temperature elevation simulations in magnetic nanoparticle hyperthermia

2013 ◽  
Vol 29 (8) ◽  
pp. 730-738 ◽  
Author(s):  
Alexander LeBrun ◽  
Navid Manuchehrabadi ◽  
Anilchandra Attaluri ◽  
Frank Wang ◽  
Ronghui Ma ◽  
...  
Keyword(s):  
Magnetic Nanoparticle ◽  
Temperature Elevation ◽  
Magnetic Nanoparticle Hyperthermia

Temperature Elevations in Implanted Prostatic Tumors in Mice During Magnetic Nanoparticle Hyperthermia: In Vivo Experimental Study

2011 ◽  
Author(s):  
Anilchandra Attaluri ◽  
Ronghui Ma ◽  
Liang Zhu
Keyword(s):  
Magnetic Field ◽  
Infusion Rate ◽  
Magnetic Nanoparticle ◽  
Animal Experiments ◽  
Intratumoral Injection ◽  
Temperature Elevation ◽  
Nanoparticle Distribution ◽  
Slow Infusion ◽  
Magnetic Nanoparticle Hyperthermia

In this study, we perform in vivo animal experiments on implanted prostatic tumors in mice to measure temperature elevation distribution in the tumor during magnetic nanoparticle hyperthermia. Temperature rises are induced by a commercially available ferrofluid injected to the center of the tumor, which is subject to an alternating magnetic field. Temperature mapping in the implanted prostatic tumors during the heating has illustrated the feasibility of elevating the tumor temperature higher than 50°C using only 0.1 cc ferrofluid injected in the tumor and under a relatively low magnetic field (3 kA/m). Ferrofluid infusion rates during intratumoral injection may affect nanoparticle spreading in tumors. Using a very slow infusion rate of 5 μ1/min results in an average temperature elevation in tumors 27°C above the baseline temperatures of 37°C. However, the temperature elevations are barely 14°C when the infusion rate is 20 μl/min. Our results suggest a more confined nanoparticle distribution to the injection site using smaller infusion rates.

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