Ronghui Ma

Controlling nanoparticle delivery in magnetic nanoparticle hyperthermia for cancer treatment: Experimental study in agarose gel

In magnetic nanoparticle hyperthermia for cancer treatment, controlling the heat distribution and temperature elevations is an immense challenge in clinical applications. In this study we evaluate magnetic nanofluid transport and heat distribution induced by commercially available magnetic nanoparticles injected into the extracellular space of biological tissue using agarose gel with porous structures similar to human tissue. The nanofluid distribution in the gel is examined via digital images of the nanofluid spreading in the gel. A radio-frequency electromagnetic field is applied to the gel following the nanofluid injection and the initial rates of temperature rise at various locations are measured to obtain the specific absorption rate (SAR) distribution. By adjusting the gel concentration and injection flow rate, the results have demonstrated that a relatively low injection rate leads to a spherically shaped nanofluid distribution in the gels which is desirable for controlling temperature elevations. The SAR distribution shows that the nanoparticle distribution in the gel is not uniform with a high concentration of the nanoparticles close to the injection site. We believe that the experimental study is the first step towards providing guidance for designing better treatment protocol for future clinical applications.

Enhancement in treatment planning for magnetic nanoparticle hyperthermia: Optimization of the heat absorption pattern

In clinical applications of magnetic nanoparticle hyperthermia for cancer treatment it is very important to ensure a maximum damage to the tumor while protecting the normal tissue. The resultant heating pattern by the nanoparticle distribution in tumor is closely related to the injection parameters. In this study we develop an optimization algorithm to inversely determine the optimum heating patterns induced by multiple nanoparticle injections in tumor models with irregular geometries. The injection site locations, thermal properties of tumor and tissue, and local blood perfusion rates are used as inputs to the algorithm to determine the optimum parameters of the heat sources for all nanoparticle injection sites. The design objective is to elevate the temperature of at least 90% of the tumor above 43°C, and to ensure only less than 10% of the normal tissue is heated to temperatures of 43°C or higher. The efficiency, flexibility and capability of this approach have been demonstrated in a case study of two tumors with simple or complicated geometry. An extensive experimental database should be developed in the future to relate the optimized heating pattern parameters found in this study to their appropriate nanoparticle concentration, injection amount, and injection rate. We believe that the optimization algorithm developed in this study can be used as a guideline for physicians to design an optimal treatment plan in magnetic nanoparticle hyperthermia.

An in-vivo experimental study of temperature elevations in animal tissue during magnetic nanoparticle hyperthermia

In magnetic nanoparticle hyperthermia in cancer treatment, the local blood perfusion rate and the amount of nanofluid delivered to the target region are important factors determining the temperature distribution in tissue. In this study, we evaluate the effects of these factors on the heating pattern and temperature elevations in the muscle tissue of rat hind limbs induced by intramuscular injections of magnetic nanoparticles during in vivo experiments. Temperature distribution in the vicinity of the injection site is measured inside the rat limb after the nanoparticle hyperthermia. The measured temperature elevations at the injection site are 3.5° ± 1.8°C and 6.02° ± 0.8°C above the measured body temperature, when the injection amount is 0.1 cc and 0.2 cc, respectively. The full width of half maximum (FWHM) of the temperature elevation, an index of heat transfer in the radial direction from the injection site is found to be approximately 31 mm for both injection amounts. The temperature measurements, together with the measured blood perfusion rate, ambient air temperature, and limb geometry, are used as inputs into an inverse heat transfer analysis for evaluation of the specific absorption rate (SAR) by the nanoparticles. It has been shown that the nanoparticles are more concentrated in the vicinity of the injection site when the injection amount is bigger. The current in vivo experimental studies have demonstrated the feasibility of elevating the tissue temperature above 43°C under the experimental protocol and equipment used in this study.

Nanoparticle distribution and temperature elevations in prostatic tumours in mice during magnetic nanoparticle hyperthermia

Among a variety of hyperthermia methods, magnetic nanoparticle hyperthermia is a highly promising approach for its confined heating within the tumour. In this study we perform in vivo animal experiments on implanted prostatic tumours in mice to measure temperature distribution in the tumour during magnetic nanoparticle hyperthermia. Temperature elevations are induced by a commercially available ferrofluid injected via a single injection to the centre of the tumour, when the tumour is subject to an alternating magnetic field. Temperature mapping in the tumours during magnetic nanoparticle hyperthermia has demonstrated the feasibility of elevating tumour temperatures higher than 50°C using only 0.1 cm3 ferrofluid injected in the tumour under a relatively low magnetic field (3 kA/m). Detailed 3-D nanoparticle concentration distribution is quantified using a high-resolution microCT imaging system. The calculated nanoparticle distribution volume based on the microCT scans is useful to analyse nanoparticle deposition in the tumours. Slower ferrofluid infusion rates result in smaller nanoparticle distribution volumes in the tumours. Nanoparticles are more confined in the vicinity of the injection site with slower infusion rates, causing higher temperature elevations in the tumours. The increase in the nanoparticle distribution volume in the tumour group after the heating from that in the tumour group without heating suggests possible nanoparticle re-distribution in the tumours during the heating.

Integrated process modeling and experimental validation of silicon carbide sublimation growth

A model that integrates heat and mass transfer, growth kinetics, anisotropic thermal stresses is developed to predict the global temperature distribution, growth rate and dislocation distribution. The simulated temperature and growth rate are compared with the experimental measurements. The time-depending growth process, e.g., the variations of the growth rate, the growth interface shape, and the thermal stresses with time in the growing crystal are studied using the integrated model. The resolved shear stress and the von Mises stress are used to predict the dislocation density. The effects of geometric configuration and design parameters on the growth of crystal are also discussed.

Multi-scale study of nanoparticle transport and deposition in tissues during an injection process

In magnetic nanoparticle hyperthermia for cancer treatment, controlling the nanoparticle distribution delivered in tumors is vital for achieving an optimum distribution of temperature elevations that enables a maximum damage of the tumorous cells while minimizing the heating in the surrounding healthy tissues. A multi-scale model is developed in this study to investigate the spatial distribution of nanoparticles in tissues after nanofluid injection into the extracellular space of tissues. The theoretical study consists of a particle trajectory tracking model that considers particle–surface interactions and a macroscale model for the transport of nanoparticles in the carrier solution in a porous structure. Simulations are performed to examine the effects of a variety of injection parameters and particle properties on the particle distribution in tissues. The results show that particle deposition on the cellular structure is the dominant mechanism that leads to a non-uniform particle distribution. The particle penetration depth is sensitive to the injection rate and surface properties of the particles, but relatively insensitive to the injected volume and concentration of the nanofluid.

Modeling of silicon carbide crystal growth by physical vapor transport method

A numerical model has been developed to study heat transfer in a silicon carbide crystal growth system. Both the electromagnetic field and temperature distribution are calculated and the effects of as-grown crystal length and coil current on temperature field are investigated. An order-of-magnitude analysis and one-dimensional network model are also employed to investigate the transport phenomena in the growth system. The results obtained from the network analysis compare well with the two-dimensional simulations. The interface temperature is found to increase with the ingot length, and a nonlinear relationship exists between the maximum temperature in the furnace and electric current.

Growth kinetics and thermal stress in AlN bulk crystal growth

Group III nitrides, such as GaN, AlN and InGaN, have attracted great attention due to their applications in blue-green and ultraviolet light emitting diodes and lasers. In this paper, an integrated model has been developed based on the conservation of momentum, mass, chemical species and energy together with boundary conditions that account for heterogeneous chemical reactions both at the source and seed surfaces. The predicted temperature profiles have been compared with measurements for different power levels and flow rates in a reactor for AlN crystal growth at the North Carolina State University. We have found that the heat power level affects the entire temperature distribution greatly while the flow rate has insignificant effect on the temperature distribution; the overall thermal stress level is higher than the critical resolved shear stress, indicating that thermal elastic stress can be a major source to induce high dislocation density in the as-grown crystal. The stress level is strongly dependent on the temperature gradient in the as-grown crystal. Results are correlated well with defects showing in an X-ray topograph for the AlN plate crystal.

Numerical study of nanofluid infusion in deformable tissues for hyperthermia cancer treatments

Direct infusion by means of needles is one of the widely used methods for the delivery of nanoparticles in tumors for hyperthermia cancer treatments. During an infusion process, infusion-induced deformation can substantially affect the dispersion of the nanoparticles injected in a biological tissue. In this study, a poroelastic model is developed to investigate fluid transport and flow-induced tissue deformation in a tumor during an infusion process. A surface tracking technique is employed to predict the shape of nanofluid spreading after injection. The model is then used to simulate the formation of backflow and the change of tissue porosity due to the deformation. Specifically, we quantify the influence of the backflow on the spreading shape of the nanofluid and its dependence on injection parameters such as infusion rates, needle diameters, and tumor elastic properties. It is found that backflow is an important factor causing an irregular distribution of the nanofluid injected in a tumor. A higher infusion rate, larger needle diameter, and lower elastic modulus yield a longer backflow length and cause a more irregular spreading shape of the nanofluid. The infusion-induced tissue deformation also leads to a pore swelling and an increase of the porosity in the vicinity of the needle tip and the needle outer surface. It is anticipated that the increased pore size may facilitate the particle penetration in a tumor. To achieve a controlled heat generation, the injection parameters should be selected judiciously with the consideration of tumor sizes, tumor properties, and thresholds at which tumors break under the infusion pressure.

THERMAL SYSTEM DESIGN AND DISLOCATION REDUCTION FOR GROWTH OF WIDE BAND-GAP CRYSTALS: APPLICATION TO SIC GROWTH

In SiC vapor growth, micropipes and dislocations that originate at the seed/boule interface can continuously propagate into the newly grown crystal and adversely affect the quality of the crystals. The defect density can be reduced by the method of growing a large diameter crystal from a small seed through lateral growth under controlled thermal environment. In this paper, SiC growth processes with varying thermal conditions have been simulated; the shapes of the as-grown crystals are predicted and the thermo-elastic stress fields in the crystals are calculated to describe the dislocation density distributions. The simulation results show that if thermal conditions are properly controlled, it is possible to reduce the micropipe density through lateral growth without increasing basal plane dislocation density. The effects of operational parameters such as the axial and radial temperature gradients and seed mounting technique on the size and quality of the crystals are also investigated. The ceramic polycrystalline material that grows on the crystal periphery is illustrated to jeopardize the quality of the crystals. In addition, the influences of some geometrical parameters on thermal environments in the growth chamber are also analyzed. The current finding can also help in the design of AlN/GaN growth system.