Ion flux, transmembrane potential, and osmotic stabilization: A new electrophysiological dynamic model for Eukaryotic cells

International audienceSurvival of mammalian cells is achieved by tight control of cell volume while transmembrane potential is known to control many cellular functions since the seminal work of Hodgkin and Huxley. Regulation of cell volume and transmembrane potential have a wide range of implications in physiology, from neurological and cardiac disorders to cancer and muscle fatigue. Therefore understanding the relationship between transmembrane potential, ion fluxes, and cell volume regulation has become of great interest. In this paper we derive a system of differential equations that links transmembrane potential, ionic concentrations, and cell volume. This model demonstrates that volume stabilization occurs within minutes of changes in extracellular osmotic pressure. We infer a straightforward relationship between transmembrane potential and cell volume. Our model is a generalization of previous models in which either cell volume was constant or osmotic regulation instantaneous. When the extracellular osmotic pressure is constant, the cell volume varies as a function of transmembrane potential and ions fluxes thus providing an implicit link between transmembrane potential and cell growth. Numerical simulations of the model provide results that are consistent with experimental data in terms of time-related changes in cell volume and dynamics of the phenomena

A model-strengthened imaging biomarker for survival prediction in EGFR-mutated non-small-cell lung carcinoma patients treated with tyrosine kinase inhibitors

International audienceNon-small-cell lung carcinoma is a frequent type of lung cancer with a bad prognosis. Depending on the stage, genomics, several therapeutical approaches are used. Tyrosine Kinase Inhibitors (TKI) may be successful for a time in the treatment of EGFR-mutated non-small cells lung carcinoma. Our objective is here to propose a survival assessment as their efficacy in the long run is challenging to evaluate. The study includes 17 patients diagnosed as of EGFR-mutated non-small cell lung cancer and exposed to an EGFR-targeting TKI with 3 computed tomography (CT) scans of the primitive tumor (one before the TKI introduction and two after). An imaging biomarker based on the texture heterogeneity evolution between the first and the third exams is derived and computed from a mathematical model and patient data. Defining the overall survival as the time between the introduction of the TKI treatment and the patient death, we obtain a statistically significant correlation between the overall survival and our imaging marker (p = 0:009). Using the ROC curve, the patients are separated into two populations and the comparison of the survival curves is statistically significant (p = 0:025). The baseline exam seems to have a significant role in the prediction of response to TKI treatment. More precisely, our imaging biomarker defined using only the CT scan before the TKI introduction allows to determine a first classification of the population which is improved over time using the imaging marker as soon as more CT scans are available. This exploratory study leads us to think that it is possible to obtain a survival assessment using only few CT scans of the primary tumor

Intensity Harmonization Techniques Influence Radiomics Features and Radiomics-based Predictions in Sarcoma Patients

International audienceIntensity harmonization techniques (IHT) are mandatory to homogenize multicentric MRIs before any quantitative analysis because signal intensities (SI) do not have standardized units. Radiomics combine quantification of tumors' radiological phenotype with machine-learning to improve predictive models, such as metastasticrelapse-free survival (MFS) for sarcoma patients. We post-processed the initial T2weighted-imaging of 70 sarcoma patients by using 5 IHTs and extracting 45 radiomics features (RFs), namely: classical standardization (IHTstd), standardization per adipose tissue SIs (IHTfat), histogram-matching with a patient histogra

MRI-Based Radiomics Input for Prediction of 2-Year Disease Recurrence in Anal Squamous Cell Carcinoma

International audiencePurpose: Chemo-radiotherapy (CRT) is the standard treatment for non-metastatic anal squamous cell carcinomas (ASCC). Despite excellent results for T1-2 stages, relapses still occur in around 35% of locally advanced tumors. Recent strategies focus on treatment intensification, but could benefit from a better patient selection. Our goal was to assess the prognostic value of pre-therapeutic MRI radiomics on 2-year disease control (DC). Methods: We retrospectively selected patients with non-metastatic ASCC treated at the CHU Bordeaux and in the French FFCD0904 multicentric trial. Radiomic features were extracted from T2-weighted pre-therapeutic MRI delineated sequences. After random division between training and testing sets on a 2:1 ratio, univariate and multivariate analysis were performed on the training cohort to select optimal features. The correlation with 2-year DC was assessed using logistic regression models, with AUC and accuracy as performance gauges, and the prediction of disease-free survival using Cox regression and Kaplan-Meier analysis. Results: A total of 82 patients were randomized in the training (n = 54) and testing sets (n = 28). At 2 years, 24 patients (29%) presented relapse. In the training set, two clinical (tumor size and CRT length) and two radiomic features (FirstOrder_Entropy and GLCM_JointEnergy) were associated with disease control in univariate analysis and included in the model. The clinical model was outperformed by the mixed (clinical and radiomic) model in both the training (AUC 0.758 versus 0.825, accuracy of 75.9% versus 87%) and testing (AUC 0.714 versus 0.898, accuracy of 78.6% versus 85.7%) sets, which led to distinctive high and low risk of disease relapse groups (HR 8.60, p = 0.005). Conclusion: A mixed model with two clinical and two radiomic features was predictive of 2-year disease control after CRT and could contribute to identify high risk patients amenable to treatment intensification with view of personalized medicine

Propagation d'impulsion laser ultracourtes dans un cristal non linéaire

11 pagesIn this paper, we present a mathematical model for ultrashort pulses propagation in nonlinear optical crystals. For ultrashort pulses, classical models based on the slowly varying envelope approximation are no longer relevant. The microscopic model based on the Maxwell-Bloch model, that we present, can accurately describe the wave-propagation while accounting for dispersive nonlinearities. We will describe this model and its numerical discretization in two dimensions of space. Finally, we perform two numerical experiments

Computational modeling of ultrashort powerful laser pulses in a nonlinear crystal

International audienceThis article presents a scheme for a semi-classical model of electromagnetic wave propagation in a non-centro-symmetric crystal of KDP. The model was throughfully described in [A Maxwell–Bloch model with discrete symmetries for wave propagation in nonlinear crystals: an application to KDP (submitted)]. It uses Maxwell's equations to describe the wave field and Bloch's equations for the medium at the quantum-mechanical level. We extend the Yee [Computational Electrodynamics: The Finite-difference Time-domain Method, second ed., Artech House, Boston, MA, 2000; IEEE Trans. Antennas Propag. AP-14 (1966) 302] scheme, in the undimensional case, used for isotropic media to treat the case of a KDP crystal, while ensuring an accurate scheme. Finally, several numerical simulations are performed

Une méthode spectrale pour les équations de Maxwell–Bloch bidimensionnelles dans les cristaux non-linéaires

International audiencePour étudier la propagation d'impulsions ultra-courtes dans un cristal non-linéaire, il est nécessaire de développer de nouveaux modèles mathématiques. Les modèles de l'optique non-linéaire classique ne sont pas adaptés pour ces impulsions à spectre large. Nous avons développé un modèle adapté à l'interaction lumière-matière dans des cristaux non-linéaires [Besse et al., Math. Model. Numer. Anal. 38 (2) (2004) 321–344]. Une étude numérique bidimensionnelle basée sur un schéma de Yee [IEEE Trans. Antennas Propag. 14 (1966) 302–307] a été effectuée ailleurs. Pour diminuer le coût numérique et la complexité d'une telle étude, nous présentons ici une nouvelle discrétisation des équations de Maxwell–Bloch basé sur une méthode spectrale [Liu, Microwave Opt. Techn. Lett. 15 (1997) 158–165]

Bidimensional study of the Maxwell-Bloch model in a nonlinear crystal

This article presents a numerical scheme for a model ([5]) of electro- magnetic wave propagation in a nonlinear optical crystal in two dimensions in space. It uses Maxwell's equations to describe the wave field and Bloch's equations for the medium at the quantum-mechanical level. We have al- ready described the discretization of the model in the unidimensional case in [14]. In this paper, we discretize the model in the bidimensional case, while ensuring a scheme of order 2. Finally, several numerical simulations are performed. We insist on physical effects that could not be observed with an unidimensional model

Propagation d'impulsion laser ultracourtes dans un cristal non linéaire

In this paper, we present a mathematical model for ultrashort pulses propagation in nonlinear optical crystals. For ultrashort pulses, classical models based on the slowly varying envelope approximation are no longer relevant. The microscopic model based on the Maxwell-Bloch model, that we present, can accurately describe the wave-propagation while accounting for dispersive nonlinearities. We will describe this model and its numerical discretization in two dimensions of space. Finally, we perform two numerical experiments