RESUMEN
Thermal ablation is a well-established successful treatment for cardiac arrhythmia, but it still presents limitations that require further studies and developments. In the rotor-driven functional re-entry arrhythmia, tissue heterogeneity results on the generation of spiral/scroll waves and wave break dynamics that may cause dangerous sustainable fibrillation. The selection of the target region to perform thermal ablation to mitigate this type of arrhythmia is challenging, since it considerably affects the local electrophysiology dynamics. This work deals with the numerical simulation of the thermal ablation of a cardiac muscle tissue and its effects on the dynamics of rotor-driven functional re-entry arrhythmia. A non-homogeneous two-dimensional rectangular region is used in the present numerical analysis, where radiofrequency ablation is performed. The electrophysiology problem for the propagation of the action potential in the cardiac tissue is simulated with the Fenton-Karma model. Thermal damage caused to the tissue by the radiofrequency heating is modeled by the Arrhenius equation. The effects of size and position of a heterogeneous region in the original muscle tissue were first analyzed, in order to verify the possible existence of the functional re-entry arrhythmia during the time period considered in the simulations. For each case that exhibited re-entry arrhythmia, six different ablation procedures were analyzed, depending on the position of the radiofrequency electrode and heating time. The obtained results revealed the effects of different model parameters on the existence and possible mitigation of the functional re-entry arrhythmia.
Asunto(s)
Ablación por Catéter , Modelos Cardiovasculares , Potenciales de Acción/fisiología , Arritmias Cardíacas/cirugía , Electrofisiología Cardíaca , Ablación por Catéter/métodos , HumanosRESUMEN
Drug delivery to tumors suffers from poor solubility, specificity, diffusion through the tumor micro-environment and nonoptimal interactions with components of the extracellular matrix and cell surface receptors. Nanoparticles and drug-polymer complexes address many of these problems. However, large size exasperates the problem of slow diffusion through the tumor. Three-dimensional tumor spheroids are good models to evaluate approaches to mitigate these difficulties and aid in design strategies to improve the delivery of drugs to treat cancer effectively. Diffusion of drug carriers is highly dependent on cell uptake rate parameters (association/dissociation) and temperature. Hyperthermia increases molecular transport and is known to act synergistically with chemotherapy to improve treatment. This study presents a new inverse estimation approach based on Bayesian probability for estimating nanoparticle cell uptake rates from experiments. The parameters were combined with a finite element computational model of nanoparticle transport under hyperthermia conditions to explore its effect on tumor porosity, diffusion and particle binding (association and dissociation) at cell surfaces. Carboxy-PEG-silane (cPEGSi) nanoparticles showed higher cell uptake compared to methoxy-PEG-silane (mPEGSi) nanoparticles. Simulations were consistent with experimental results from Skov-3 ovarian cancer spheroids. Amorphous silica (cPEGSi) nanoparticles (58 nm) concentrated at the periphery of the tumor spheroids at 37°C but mild hyperthermia (43°C) increased nanoparticle penetration. Thus, hyperthermia may enhance cancer treatment by improving blood delivery to tumors, enhancing extravasation and penetration into tumors, trigger release of drug from the carrier at the tumor site and possibly lead to synergistic anti-cancer activity with the drug.
Asunto(s)
Hipertermia Inducida , Nanopartículas , Neoplasias , Teorema de Bayes , Simulación por Computador , Humanos , Hipertermia , Neoplasias/tratamiento farmacológico , Dióxido de Silicio , Esferoides Celulares , Microambiente TumoralRESUMEN
Cancer is characterized by the uncontrolled growth of cells with the ability of invading local organs and/or tissues and of spreading to other sites. Several kinds of mathematical models have been proposed in the literature, involving different levels of refinement, for the evolution of tumors and their interactions with chemotherapy drugs. In this article, we present the solution of a state estimation problem for tumor size evolution. A system of nonlinear ordinary differential equations is used as the state evolution model, which involves as state variables the numbers of tumor, normal and angiogenic cells, as well as the masses of the chemotherapy and anti-angiogenic drugs in the body. Measurements of the numbers of tumor and normal cells are considered available for the inverse analysis. Parameters appearing in the formulation of the state evolution model are treated as Gaussian random variables and their uncertainties are taken into account in the estimation of the state variables, by using an algorithm based on the auxiliary sampling importance resampling particle filter. Test cases are examined in the article dealing with a chemotherapy protocol for pancreatic cancer.
Asunto(s)
Neoplasias/patología , Algoritmos , Antimetabolitos Antineoplásicos/farmacocinética , Simulación por Computador , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacocinética , Diagnóstico por Computador , Semivida , Humanos , Modelos Biológicos , Método de Montecarlo , Neoplasias/tratamiento farmacológico , Carga Tumoral , GemcitabinaRESUMEN
The main objective of this work was to demonstrate computationally that realistic human hearts can be cooled much faster by performing conjugate heat transfer consisting of pumping a cold liquid through the cardiac chambers and major veins while keeping the heart submerged in cold gelatin filling a cooling container. The human heart geometry used for simulations was obtained from three-dimensional, high resolution CT-angio scans. Two fluid flow domains for the right (pulmonic) and left (systemic) heart circulations, and two solid domains for the heart tissue and gelatin solution were defined for multi-domain numerical simulation. Detailed unsteady temperature fields within the heart tissue were calculated during the conjugate cooling process. A linear thermoelasticity analysis was performed to assess the stresses applied on the heart due to the coolant fluid shear and normal forces and to examine the thermal stress caused by temperature variation inside the heart. It was demonstrated that a conjugate cooling effort with coolant temperature at +4°C is capable of reducing the average heart temperature from +37°C to +8°C in 25 minutes for cases in which the coolant was steadily pumped only through major heart inlet veins and cavities.
Asunto(s)
Corazón/fisiología , Simulación por Computador , Gelatina/química , Humanos , Preservación de Órganos , Programas Informáticos , Estrés Fisiológico , Temperatura , Factores de TiempoRESUMEN
Rapid cooling of the brain in the first minutes following the onset of cerebral ischemia is a potentially attractive preservation method. This computer modeling study was undertaken to examine brain-cooling profiles in response to various external cooling methods and protocols, in order to guide the development of cooling devices suitable for deployment on emergency medical vehicles. The criterion of successful cooling is taken to be the attainment of a 33 degrees C average brain temperature within 30 min of treatment. The transient cooling of an anatomically correct realistic 3-D head and neck with realistically varying local tissue properties was numerically simulated using the finite-element method (FEM). The simulations performed in this study consider ice packs applied to head and neck as well as using a head-cooling helmet. However, it was found that neither of these cooling approaches satisfies the 33 degrees C temperature within 30 min. This central conclusion of insubstantial cooling is supported by the modest enhancements reported in experimental investigations of externally applied cooling. The key problem is overcoming the protective effect of warm blood perfusion, which reaches the brain via the uncooled carotid arterial supply and effectively blocks the external cooling wave from advancing to the core of the brain. The results show that substantial cooling could be achieved in conjunction with neck cooling if the blood speed in the carotid artery is reduced from normal by a factor of 10. The results suggest that additional cooling means should be explored, such as cooling of other pertinent parts of the human anatomy.