PurposeRadioiodine therapy (RAI) has traditionally been used as treatment for metastatic thyroid cancer, based on its ability to concentrate iodine. Propositions to maximize tumor response with minimizing toxicity, must recognize the infinite possibilities of empirical tests. Therefore, an approach of this study was to build a mathematical model describing tumor growth with the kinetics of thyroglobulin (Tg) concentrations over time, following RAI for metastatic thyroid cancer.Experimental DesignData from 50 patients with metastatic papillary thyroid carcinoma treated within eight French institutions, followed over 3 years after initial RAI treatments, were included in the model. A semi-mechanistic mathematical model that describes the tumor growth under RAI treatment was designed.ResultsOur model was able to separate patients who responded to RAI from those who did not, concordant with the physicians' determination of therapeutic response. The estimated tumor doubling-time (Td was found to be the most informative parameter for the distinction between responders and non-responders. The model was also able to reclassify particular patients in early treatment stages.ConclusionsThe results of the model present classification criteria that could indicate whether patients will respond or not to RAI treatment, and provide the opportunity to perform personalized management plans.
through gap junctions has been shown to reduce such variability which may return as coupling is reduced. A phenomenological model capable of accurately capturing action potential morphology and variability observed in experimental data has been developed with tunable restitution properties. The phenomenological formulation also allows fast simulation compared with biophysically detailed models. This model is now used to investigate the effects of action potential variability over prolonged periods. A two dimensional tissue slab is simulated using a monodomain model and the simulation software Chaste. Simulations are performed with and without variability in the action potential model. Different coupling strengths are used with a physiological conductivity corresponding to a conduction velocity of 71cm/s. Simulations are performed at full conductivity, and with the conductivity scaled by factors of 0.5, 0.1 and 0.05. At a pacing cycle length of 1000ms with physiological coupling and differences in action potential duration with and without variability are negligible. Under reduced coupling, the difference increases to a maximum of 2ms. No correlation is observed between beats. At a cycle length of 230ms, temporal variability drives the cell model to alternans. This effect is reduced in tissue at all conductivities. Tissue was paced for 40 beats at a cycle length of 230ms before a cycle length reduction of 4ms. The process was repeated until propagation failed. At a cycle length of 222ms a spatially discordant alternans of magnitude 2ms was observed.In conclusion, stochastic effects are masked at physiological conductivity values and effects do not accumulate over time. At significantly reduced conductivity heterogeneities in repolarisation can be induced. We are exploring the viability of a novel approach to cardiocyte contractility assessment based on biomechanical properties of the cardiac cells, energy conservation principles, and information content measures. We define our measure of cell contraction as being the distance between the shapes of the contracting cell, assessed by the minimum total energy of the domain deformation (warping) of one cell shape into another. To guarantee a meaningful vis-à-vis correspondence between the two shapes, we employ both a data fidelity term and a regularization term. The data fidelity term is based on nonlinear features of the shapes while the regularization term enforces the compatibility between the shape deformations and that of a hyper-elastic material. We tested this approach by assessing the contractile responses in isolated adult rat cardiocytes and contrasted these measurements against two different methods for contractility assessment in the literature. Results show good qualitative and quantitative agreements with these methods as far as frequency, pacing, and overall behavior of the contractions are concerned. We hypothesize that the proposed methodology, once appropriately developed and customized, can provide a framework for computational cardiac cell biomechan...
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