Determination of time of death in forensic science via a 3-D whole body heat transfer model.

This study is focused on developing a whole body heat transfer model to accurately simulate temperature decay in a body postmortem. The initial steady state temperature field is simulated first and the calculated weighted average body temperature is used to determine the overall heat transfer coefficient at the skin surface, based on thermal equilibrium before death. The transient temperature field postmortem is then simulated using the same boundary condition and the temperature decay curves at several body locations are generated for a time frame of 24h. For practical purposes, curve fitting techniques are used to replace the simulations with a proposed exponential formula with an initial time delay. It is shown that the obtained temperature field in the human body agrees very well with that in the literature. The proposed exponential formula provides an excellent fit with an R2 value larger than 0.998. For the brain and internal organ sites, the initial time delay varies from 1.6 to 2.9h, when the temperature at the measuring site does not change significantly from its original value. The curve-fitted time constant provides the measurement window after death to be between 8h and 31h if the brain site is used, while it increases 60-95% at the internal organ site. The time constant is larger when the body is exposed to colder air, since a person usually wears more clothing when it is cold outside to keep the body warm and comfortable. We conclude that a one-size-fits-all approach would lead to incorrect estimation of time of death and it is crucial to generate a database of cooling curves taking into consideration all the important factors such as body size and shape, environmental conditions, etc., therefore, leading to accurate determination of time of death.

MicroCT image based simulation to design heating protocols in magnetic nanoparticle hyperthermia for cancer treatment.

OBJECTIVES: The objective is to design heating protocols to completely damage PC3 tumors after a single magnetic nanoparticle hyperthermia session with minimal collateral thermal damage, based on microCT image generated tumor and mouse models. METHODS: Tumor geometries and volumetric heat generation rate distributions that are generated from microCT scans in our previous study are imported into COMSOL 4.3® multiphysics for heat transfer simulations and heating protocol design using the Arrhenius damage model. Then, parametric studies are performed to evaluate how significantly the infusion rate affects the protocol design and its resulted collateral thermal damage. RESULTS: The simulated temperature field in the generated tumor geometry and volumetric heat generation rate distribution are reasonable and correlates well with the amount of the total thermal energy deposited into the tumors. The time needed for complete thermal damage is determined to be approximately 12min or 25min if one uses the Arrhenius integral Ω equal to 1 or 4 as the damage threshold, when the infusion rate is 3µL/min. The heating time increases 26% or 91% in the higher infusion rate groups of 4 or 5µL/min, respectively. Collateral thermal damage to the surrounding tissue is also assessed. Although the two larger infusion rate groups can still cause thermal damage to the entire tumor, the collateral thermal damage would have exceeded the design criterion of 5%, while the assessment criterion is acceptable only in the infusion rate group of 3µL/min. Based on the results of this study, we identify an injection strategy and heating protocols to be implemented in future animal experiments to evaluate treatment efficacy for model validation.

Identification of infusion strategy for achieving repeatable nanoparticle distribution and quantification of thermal dosage using micro-CT Hounsfield unit in magnetic nanoparticle hyperthermia.

OBJECTIVES: The objective of this study was to identify an injection strategy leading to repeatable nanoparticle deposition patterns in tumours and to quantify volumetric heat generation rate distribution based on micro-CT Hounsfield unit (HU) in magnetic nanoparticle hyperthermia. METHODS: In vivo animal experiments were performed on graft prostatic cancer (PC3) tumours in immunodeficient mice to investigate whether lowering ferrofluid infusion rate improves control of the distribution of magnetic nanoparticles in tumour tissue. Nanoparticle distribution volume obtained from micro-CT scan was used to evaluate spreading of the nanoparticles from the injection site in tumours. Heating experiments were performed to quantify relationships among micro-CT HU values, local nanoparticle concentrations in the tumours, and the ferrofluid-induced volumetric heat generation rate (q(MNH)) when nanoparticles were subject to an alternating magnetic field. RESULTS: An infusion rate of 3 µL/min was identified to result in the most repeatable nanoparticle distribution in PC3 tumours. Linear relationships have been obtained to first convert micro-CT greyscale values to HU values, then to local nanoparticle concentrations, and finally to nanoparticle-induced q(MNH) values. The total energy deposition rate in tumours was calculated and the observed similarity in total energy deposition rates in all three infusion rate groups suggests improvement in minimising nanoparticle leakage from the tumours. The results of this study demonstrate that micro-CT generated q(MNH) distribution and tumour physical models improve predicting capability of heat transfer simulation for designing reliable treatment protocols using magnetic nanoparticle hyperthermia.

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

OBJECTIVES: The objective of this study was to develop and test computer algorithms to export micro computed tomography (microCT) images and to generate tumour geometry and specific absorption rate (SAR) distribution for heat transfer simulation in magnetic nanoparticle hyperthermia. METHODS: Computer algorithms were written to analyse and export microCT images of 3D tumours containing magnetic nanoparticles. MATLAB(®) and ProE(®) programs were used to generate a prototype of the tumour geometry. The enhancements in the microCT pixel index number due to presence of nanoparticles in the tumours were first converted into corresponding SAR values. The SAR data were then averaged over three-dimensional clusters of pixels using the SAS(®) program. This greatly decreased the size of the SAR file, while in the meantime it ensured that the amount of total energy deposited in the tumour was conserved. Both the tumour geometry and the SAR file were then imported into the COMSOL(®) software package to simulate temperature elevations in the tumour and their surrounding tissue region during magnetic nanoparticle hyperthermia. RESULTS: A linear relationship was obtained to relate individual pixel index numbers in the microCT images to the SAR values under a specific magnetic field. The generated prototype of the tumour geometry based on only 30 slices of microCT images resembled the original tumour shape and size. The tumour geometry and the simplified SAR data set were successfully accepted by the COMSOL software for heat transfer simulation. Up to 20 °C temperature elevations from its baseline temperature were found inside the tumours, implying possible thermal damage to the tumour during magnetic nanoparticle hyperthermia.

Computational simulation of temperature elevations in tumors using Monte Carlo method and comparison to experimental measurements in laser photothermal therapy.

Accurate simulation of temperature distribution in tumors induced by gold nanorods during laser photothermal therapy relies on precise measurements of thermal, optical, and physiological properties of the tumor with or without nanorods present. In this study, a computational Monte Carlo simulation algorithm is developed to simulate photon propagation in a spherical tumor to calculate laser energy absorption in the tumor and examine the effects of the absorption (µ(a)) and scattering (µ(s)) coefficients of tumors on the generated heating pattern in the tumor. The laser-generated energy deposition distribution is then incorporated into a 3D finite-element model of prostatic tumors embedded in a mouse body to simulate temperature elevations during laser photothermal therapy using gold nanorods. The simulated temperature elevations are compared with measured temperatures in PC3 prostatic tumors in our previous in vivo experimental studies to extract the optical properties of PC3 tumors containing different concentrations of gold nanorods. It has been shown that the total laser energy deposited in the tumor is dominated by µ(a), while both µ(a) and µ(s) shift the distribution of the energy deposition in the tumor. Three sets of µ(a) and µ(s) are extracted, representing the corresponding optical properties of PC3 tumors containing different concentrations of nanorods to laser irradiance at 808 nm wavelength. With the injection of 0.1 cc of a 250 optical density (OD) nanorod solution, the total laser energy absorption rate is increased by 30% from the case of injecting 0.1 cc of a 50 OD nanorod solution, and by 125% from the control case without nanorod injection. Based on the simulated temperature elevations in the tumor, it is likely that after heating for 15 min, permanent thermal damage occurs in the tumor injected with the 250 OD nanorod solution, while thermal damage to the control tumor and the one injected with the 50 OD nanorod solution may be incomplete.