Biological heat and mass transport mechanisms behind nanoparticles migration revealed under microCT image guidance

Abstract

Background and objectivesBlood perfusion, infusion rate, distribution and heating induced redistribution of magnetic nanoparticles inside tumour interstitium governs the heating protocol designs. This study aims to answer three important questions: Why do magnetic nanoparticles redistributes? What causes their migration? Why it is important to be included in priori-treatment planning simulations? Our aim is to test how the regulation of magnetic nanoparticles affects the temperature distribution and how this temperature change modifies tumour microenvironment. We have tested our hypothesis for two cases: (1) when the nanoparticles are lying in close proximity to the flank position of tumour i.e. near the interface of tumour and healthy tissue and (2) when the nanoparticles are located near the skin surface of tumour. Materials and methodsSAS® and MATLAB programs are used to average micro-CT cross-sectional slices containing three-dimensional clusters of pixels corresponds to nanoparticles as a SAR file and Concentration distribution file import to the COMSOL-Multiphysics® 5.2 FEA software for evaluation of temperature distribution and its resulted collateral thermal damage. The volumetric heat generation rate (qMNH‴) is kept ∼ 0.37 W for infusion rate of 4 μL/min. Pennes bioheat equation is three-way coupled with traditional Arrhenius thermal damage model, modified concentration equation in which heat source term (SAR) varies in a directly proportional relationship with Concentration distribution. All variables i.e. Diffusion coefficient, porosity, blood perfusion, metabolic heat generation are varying as a function of thermal damage for a coupled biophysics problem. ResultsThermal signatures of cell-death were evaluated for two case scenarios. The initial distribution volume is 188.46 mm3. On compare and contrast, 6.24% larger thermal diffusion is seen at outer extremities case than at the interface. However, the treatment times are 12.90% (1.13 fold more) to achieve a Ω ≥ 4.6 with ΔT=10°C for latter case. On evaluation of “Source maps” (before heating) with “Destination maps” (after heating) suggests migration of nanoparticles from the regions of higher concentration to the regions of lower concentration due to cell-necrosis induced enhancement in tumour interstitial space. Thermal-diffusion of nanoparticles suggests an increase in redistribution volumes by 23.44% and 26.30% respectively during 99.6% transformation of cancerous cells. This study precisely elucidate qualitative and quantitative aspects of this issue. One of the possible reasons of nanoparticle migration is that the dead cells release intracellular solution after the rupturing of cell membrane. We speculate that five-fold increase in diffusion coefficient of nanoparticles might have played a significant role in particle migration. ConclusionsCNIDC (Cell necrosis induced diffusivity change) and CNIPE (Cell necrosis induced porosity enhancement) may be the two intricate mechanisms that promotes nanoparticles migration.