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

Author(s):  
Anilchandra Attaluri ◽  
Ronghui Ma ◽  
Liang Zhu

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.

Author(s):  
Maher Salloum ◽  
Ronghui Ma ◽  
Liang Zhu

Magnetic nanoparticle hyperthermia has potential to achieve optimal therapeutic results due to its ability to deliver adequate heating power to irregular and/or deep-seated tumor at low magnetic field frequency and amplitude [1]. The heat generated by the particles under the application of an external alternating magnetic field is mainly due to the Néel relaxation mechanism and/or Brownian motion of the particles [2]. In clinical applications, it is very important to ensure a maximum damage to the tumor while protecting the normal tissue. The resulted heating pattern by the nanoparticle distribution in tumor is closely related to the injection parameters [3, 4].


Author(s):  
Di Su ◽  
Ronghui Ma ◽  
Liang Zhu

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.


2020 ◽  
Vol 142 (7) ◽  
Author(s):  
Manpreet Singh ◽  
Qimei Gu ◽  
Ronghui Ma ◽  
Liang Zhu

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.


Author(s):  
Maher Salloum ◽  
Ronghui Ma ◽  
Liang Zhu

Magnetic nanoparticle hyperthermia has potential to achieve optimal therapeutic results due to its ability to deliver adequate heating power to irregular and/or deep-seated tumor at low magnetic field frequency and amplitude [1]. Iron oxides magnetite Fe3O4 and maghemite γ-Fe2O3 nanoparticles are the most studied to date [2] due to their biocompatibilty [3] for hyperthermia application. The heat generated by the particles when exposed to an external alternating magnetic field is mainly due to the Néel relaxation mechanism and/or Brownian motion of the particles [4]. The superparamagnetic particles (10–40 nm) are recommended in clinical application as they are able to generate substantial heat within a small magnetic field strength and frequency [5].


2019 ◽  
Vol 141 (3) ◽  
Author(s):  
Qimei Gu ◽  
Tejashree Joglekar ◽  
Charles Bieberich ◽  
Ronghui Ma ◽  
Liang Zhu

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.


Sensors ◽  
2021 ◽  
Vol 21 (16) ◽  
pp. 5545 ◽  
Author(s):  
Izaz Raouf ◽  
Piotr Gas ◽  
Heung Soo Kim

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.


1994 ◽  
Vol 17 (3) ◽  
pp. 155-162 ◽  
Author(s):  
G.J. Verkerke ◽  
H. Schraffordt Koops ◽  
R.P.H. Veth ◽  
H.J. Grootenboer ◽  
L.J. De Boer ◽  
...  

A malignant bone tumour may develop in the femur of a child. In the majority of cases it will be necessary to resect the bone involved, growth plate and adjacent tissues. A modular endoprosthetic system has been developed which can be extended non-invasively to bridge the defect resulting from such a resection. Elongation is achieved by using an external magnetic field. In vitro tests with a prototype showed that the lengthening element met all requirements. Six animal experiments showed that the lengthening element also functioned in vivo.


2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Asahi Tomitaka ◽  
Tsutomu Yamada ◽  
Yasushi Takemura

Magnetic nanoparticles are promising materials for hyperthermia treatment. The temperature rise under ac magnetic field, cytotoxicity, andin vitrohyperthermia effect of nanoparticles coated with Pluronic f-127 were evaluated in this paper. The Pluronic-coated nanoparticles exhibited no cytotoxic effect on HeLa cells. The optimal magnetic field of Pluronic-coated nanoparticles was 16 kA/m (200 Oe) at the field strength of 210 kHz. Appropriate temperature rise significantly reduced the viability of HeLa cells and induced apoptosis.


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