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.

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.

Tumor Shrinkage Study in Magnetic Nanoparticle Hyperthermia Based on Designed Heating Protocols

2016 ◽  
Author(s):  
Alexander LeBrun ◽  
Ronghui Ma ◽  
Liang Zhu
Keyword(s):  
Magnetic Nanoparticle ◽  
Theoretical Models ◽  
Control Group ◽  
Nanoparticle Deposition ◽  
Injection Strategy ◽  
Heating Treatment ◽  
Arrhenius Integral ◽  
Tumor Region ◽  
Magnetic Nanoparticle Hyperthermia

Magnetic nanoparticle hyperthermia has attracted growing attentions recently due to its ability of confining nanoparticle-induced heating in targeted tumor region. Our recent studies have identified an injection strategy to achieve repeatable and controllable nanoparticle deposition patterns in PC3 tumors using microCT scans. Based on the injection strategy, simulation of temperature elevations in tumors is conducted to design heating protocols to induce irreversible thermal damage to the entire tumors. In this study, in vivo heating experiments are performed on PC3 tumors implanted on mice following the designed heating protocols. The tumors in the control group without heating triple their sizes over a period of eight weeks. The tumors in the heating groups are heated for either 25 minutes or 12 minutes, representing that the Arrhenius integral is equal to or larger than 4 or 1 in the entire tumors, respectively. The tumors in the heating group of 25 minutes disappear completely after the 3rd days, and the site maintains the disappearance for over eight weeks. The sizes of the tumors in the heating group of 12 minutes decrease in the first ten days, however, the tumors re-grow afterwards, and by the end of the 8th week, they are approximately 60% larger than their initial size. This study demonstrates the importance of imaging-based design for individualized treatment planning. The success of the designed heating protocol in complete damaging PC3 tumors validates the theoretical models used in planning the heating treatment in magnetic nanoparticle hyperthermia.

Nanoparticle Redistribution in PC3 Tumors Induced by Local Heating in Magnetic Nanoparticle Hyperthermia: In Vivo Experimental Study

2019 ◽  
Vol 141 (3) ◽  
Author(s):  
Qimei Gu ◽  
Tejashree Joglekar ◽  
Charles Bieberich ◽  
Ronghui Ma ◽  
Liang Zhu
Keyword(s):  
Heat Generation ◽  
Magnetic Nanoparticle ◽  
Local Heating ◽  
Generation Rate ◽  
Control Group ◽  
Heat Generation Rate ◽  
Nanoparticle Distribution ◽  
Tumor Periphery ◽  
Magnetic Nanoparticle Hyperthermia

In magnetic nanoparticle hyperthermia, a required thermal dosage for tumor destruction greatly depends on nanoparticle distribution in tumors. The objective of this study is to conduct in vivo experiments to evaluate whether local heating using magnetic nanoparticle hyperthermia changes nanoparticle concentration distribution in prostatic cancer (PC3) tumors. In vivo animal experiments were performed on grafted PC3 tumors implanted in mice to investigate whether local heating via exposing the tumor to an alternating magnetic field (5 kA/m and 192 kHz) for 25 min resulted in nanoparticle spreading from the intratumoral injection site to tumor periphery. Nanoparticle redistribution due to local heating is evaluated via comparing microCT images of resected tumors after heating to those in the control group without heating. A previously determined calibration relationship between microCT Hounsfield unit (HU) values and local nanoparticle concentrations in the tumors was used to determine the distribution of volumetric heat generation rate (q‴MNH) when the nanoparticles were subject to the alternating magnetic field. sas,matlab, and excel were used to process the scanned data to determine the total heat generation rate and the nanoparticle distribution volumes in individual HU ranges. Compared to the tumors in the control group, nanoparticles in the tumors in the heating group occupied not only the vicinity of the injection site, but also tumor periphery. The nanoparticle distribution volume in the high q‴MNH range (>1.8 × 106 W/m3) is 10% smaller in the heating group, while in the low q‴MNH range of 0.6–1.8 × 106 W/m3, it is 95% larger in the heating group. Based on the calculated heat generation rate in individual HU ranges, the percentage in the HU range larger than 2000 decreases significantly from 46% in the control group to 32% in the heating group, while the percentages in the HU ranges of 500–1000 and 1000–1500 in the heating group are much higher than that in the control group. Heating PC3 tumors for 25 min resulted in significant nanoparticle migration from high concentration regions to low concentration regions in the tumors. The volumetric heat generation rate distribution based on nanoparticle distribution before or after local heating can be used in the future to guide simulation of nanoparticle redistribution and its induced temperature rise in PC3 tumors during magnetic nanoparticle hyperthermia, therefore, accurately predicting required thermal dosage for safe and effective thermal therapy.

scholarly journals Numerical Investigation of Ferrofluid Preparation during In-Vitro Culture of Cancer Therapy for Magnetic Nanoparticle Hyperthermia

Sensors ◽  
2021 ◽  
Vol 21 (16) ◽  
pp. 5545 ◽  
Author(s):  
Izaz Raouf ◽  
Piotr Gas ◽  
Heung Soo Kim
Keyword(s):  
Numerical Model ◽  
Cancer Therapy ◽  
Magnetic Nanoparticle ◽  
Research Work ◽  
Thermal Response ◽  
Linear Response Theory ◽  
Novel Approach ◽  
Magnetic Nanoparticle Hyperthermia

Recently, in-vitro studies of magnetic nanoparticle (MNP) hyperthermia have attracted significant attention because of the severity of this cancer therapy for in-vivo culture. Accurate temperature evaluation is one of the key challenges of MNP hyperthermia. Hence, numerical studies play a crucial role in evaluating the thermal behavior of ferrofluids. As a result, the optimum therapeutic conditions can be achieved. The presented research work aims to develop a comprehensive numerical model that directly correlates the MNP hyperthermia parameters to the thermal response of the in-vitro model using optimization through linear response theory (LRT). For that purpose, the ferrofluid solution is evaluated based on various parameters, and the temperature distribution of the system is estimated in space and time. Consequently, the optimum conditions for the ferrofluid preparation are estimated based on experimental and mathematical findings. The reliability of the presented model is evaluated via the correlation analysis between magnetic and calorimetric methods for the specific loss power (SLP) and intrinsic loss power (ILP) calculations. Besides, the presented numerical model is verified with our experimental setup. In summary, the proposed model offers a novel approach to investigate the thermal diffusion of a non-adiabatic ferrofluid sample intended for MNP hyperthermia in cancer treatment.

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.

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