Medical Imaging Assisted Computational Bio-heat transfer Analysis of Magnetic Nanoparticles Induced Hyperthermia for Breast Cancer

Abstract

Due to the increased concerns and burden of cancer on the world, the computational related studies plays a very pivotal role. To assist the ongoing treatment modalities, it becomes an important part of interdisciplinary research to assist nanomedicine and theranostics(therapeuticdiagnostic). Patient-specific modeling is the major area which provides the desired outcomes before implementing the treatment modalities. For this various design engineers, researchers are putting their effortsto develop and compute such algorithms. In relation to this, number of computational softwares are available that provides the reliable results extracted from MRI/CT scan images of patients anatomy. In the present work, the anatomical model of human(female) breast tissue is processed from large sets of Dicom-format(medical) images via Materialise Mimics-17.0 and 3-Matic. Three dimensional model is generated in Mimics and in 3-Matic tool desired surface layers are provided on the geometry to successfully employ boundary conditions. There is availability of sharing interface(import/export option) that save the model as mesh file(.mphtxt). For thermal analysis, this mesh file is imported into COMSOL-MULTIPHYSICS. Three dimensional model is generated from mesh file to define material(physiological) properties, initial and boundary conditions, mesh variations(grid independency test) to perform the thermal simulations. The concept of averaging of properties is used while defining material properties to nanoparticles loaded tumor to channelize the simulations and to approach towards correct results.Computational model is made by COMSOL-MULTIPHYSICS software to understand the physics behind microparticles/nanoparticles.In Comsol, two kinds of studies are performed by considering the problem study as Uncoupled analysis and One-way coupled analysis. Uncoupled analysis includes only Heat transfer module(Bio-heat transfer module) to compute temperature field distributions. While One-way coupled analysis includes the electromagnetic heating induced in particles via AC-DC module(magnetic fields with current) and Heat transfer module(Bio-heat transfer module). MATLAB is used to account for calculations of Specific absorption Rate (S.A.R)/Specific Loss Power (S.L.P) via self-written algorithms/codes. It accounts for the effect of nanoparticles and magnetic heating principles to save the results which is an important heat input to Comsol-Multiphysics simulations. Two type of variations i.e. diameter of nanoparticles v and magnetic field tunable parameter frequency are performed to calculate S.A.R.The calculated value validate the results of Chin & Tse et al. under given conditions.Values comes out to be 2 x 105W/m³ which matched with the value of 1.95 x 105W/m³ for 19nm magnetite particle. The iron-oxide particles(Magnetite) are essentially assumed to be spherical in shape and the aforementioned variables help to account for selection of effective size nanoparticles and particular frequency range at which the results will be optimum in relation to hyperthermia studies.The particles are uniformly distributed,monodispersed over the whole domain.Safe and tolerable conditions as reported by Atkinson, Brezovich, Hergt and confirmed by Pankhurst of human exposure to magnetic field through clinical trials are also put into consideration to verify computational simulation parameters. For Cancerous tissue the objective function is to maximize the temperature between 41.5°C to 46.5°C in tumor region to maintain hyperthermia for effective necrosis to be used in conjunction with chemotherapy or radiotherapy. For hyperthermia to be used as monotherapy thermal ablation of tumors in temperature range of 50°C-70°C is also been studied. For all the simulations transient analysis is used to achieve the effective results. In the present work, the first level of simulations are performed by defining computational geometry(regular geometry) which consist of two domains i.e cylindrical healthy tissue and ellipsoid cancerous tissue loaded with particles. The spatial-temporal distribution curves are generated in tissue along the horizontal and vertical axis passing through center of tumor. Multiple site intratumoral injections(homogeneous distribution and monodispersion of particles) are considered which is itself been the first effort to consider individually the temperature achieved in all injection sites. Temperature at center of tumor is also studied. Muscle tissue is considered in this analysis. In realistic case, the geometrical domains are irregular in shape. To consider this aspect, the current model is extended towards realistic tumor model of irregular shape and similar analysis is performed to analyse the temperature distributions for breast tissue. For the current study bio-heat transfer module is used and different S.A.R values(heat quantization tunable parameter) are given as an input to study temperature distributions and effective necrosis plots. The next level of study includes analytical calculations performed for tissues put under the magnetic field. It involves calculations for number of turns for coil under considerations of current and magnetic field strength. These analytical results computed for the geometry are vi verified with computational results plotted for same set of inputs and conditions. This magnetic field computed from coil is sufficient to produce heating effects via relaxation phenomenon(Néel relaxation and Brownian motion) if magnetite particles or domain containing particles is concerned. Now, the heat parameter(S.A.R) is defined asan input to bioheat transfer module by magnetic fields with current module. The temperature and magnetic field distributions curves are plotted against vertical and horizontal axis passing through the center of tumor. In this work, an extensive literature review is performed on magnetic nanoparticles(Magnetite,Maghemite,Iron-Platinum,Iron-Cobalt,Barium Ferrite, and Cobalt Ferrite) been studied till date to present all the key magnetic field parameters in single sheet and to quantify all for desired computational inputs. Microscale/nanoscale heat transfer principles to malignant tumorsis done efficiently by simultaneously trying to achieve the temperature range of 41.5°C to 46.5°C to do apoptosis. The choice of effective bio-compatible super-paramagnetic nanoparticle is proved to be an effective tool aided with other current means of Chemotherapy and radiotherapy. We propose magnetite material, an extensively studied particle for our simulations to study hyperthermia as monotherapy.For the present simulations the temperature achieved is 71°C which matched with the literature results of Hilger et al.,2001[28]. The heat quantization parameter needs to be tuned in order to select proper heat input value.Coupling between bioheat transfer module and magnetic field with current (frequency variations) are performed on muscle tissue for proper choice of magnetic nanoparticle diameter, SAR value is calculated via self written MATLAB codes and analytical calculation results are verified with literature.