Grupos Investigadores

Líneas de Investigación

  • Biofísica del Corazón
  • Fluidos
  • Modelos físicos y radiobiológicos para el cálculo de la dosis
  • Movimiento Externo del Paciente
  • Radioterapia Adaptativa y Guiada por Imagen
  • Radioterapia con Barrido Activo (Pencil Beam Scanning) en Protones

Palabras Clave

  • 4D
  • Barrido activo
  • Microdosimetría
  • Modelos Biológicos
  • Monte Carlo
  • Protonterapia
  • Radioterapia adaptativa
  • Registro deformable
  • Sincrotrón

Publicaciones Científicas desde 2018

  • Autores: Ibarz Barbera, M. (Autor de correspondencia); Hernández-Verdejo, J. L.; Bragard Monier, Jean; et al.
    Revista: PLOS ONE
    ISSN: 1932-6203 Vol.18 N° 6 2023 págs. e0286884
    PurposeTo investigate the possible risk factors for treatment failure in patients who had undergone Preserflo Microshunt (PMS) implantation, using anterior-segment optical coherence tomography (AS-OCT) to analyze the internal structures of the bleb. MethodsThe PMS blebs of 54 patients were evaluated with AS-OCT. A mathematical model was used to calculate the total filtering surface of the episcleral fluid cavity (EFC) and the hydraulic conductivity (HC) of the bleb wall. Complete and qualified success were defined as IOP between 6 and 17 mmHg with or without glaucoma medication. The relation between baseline characteristics and probability of bleb success was analyzed by bivariate and multivariate logistic regression. The main outcome measures were mean bleb wall thickness (BWT), reflectivity (BWR), HC, mean horizontal and vertical diameter and total filtering surface (TFS) of the EFC. ResultsBlebs from 74% patients were considered as complete success and 26% as failure. BWR and BWT increased linearly up to the first year in both groups. BWR was higher in the group failure (p = 0.02) and BWT in the group success (p<0.001). EFC was wider and shorter in the success group (p = 0.009, p = 0.03). Higher TFS showed a negative correlation with IOP (r = -0.4, p = 0.002). Higher baseline IOP was associated with success of PMS by multivariate analysis (p = 0.01). Mean HC, 0.034 +/- 0.008 (mu L/min)/mm(2)/mmHg, was negatively correlated with bleb surface (r = -0.5, p<0.0001) and wall ' s thickness (r = -0.3, p = 0.01). ConclusionsAS-OCT revealed that successful PMS blebs could show either thick hyporreflective walls or wide filtering surfaces with thin capsules. A higher baseline IOP increased the probability of surgical success.
  • Autores: Huesa Berral, Carlos; Juan-Cruz, C.; van Kranen, S.; et al.
    ISSN: 0031-9155 Vol.68 N° 1 2023 págs. 015005
    Objective. Periodic respiratory motion and inter-fraction variations are sources of geometric uncertainty in stereotactic body radiation therapy (SBRT) of pulmonary lesions. This study extensively evaluates and validates the separate and combined dosimetric effect of both factors using 4D-CT and daily 4D-cone beam CT (CBCT) dose accumulation scenarios. Approach. A first cohort of twenty early stage or metastatic disease lung cancer patients were retrospectively selected to evaluate each scenario. The planned-dose (3D(Ref)) was optimized on a 3D mid-position CT. To estimate the dosimetric impact of respiratory motion (4D(Ref)), inter-fractional variations (3D(Acc)) and the combined effect of both factors (4D(Acc)), three dose accumulation scenarios based on 4D-CT, daily mid-cone beam CT (CBCT) position and 4D-CBCT were implemented via CT-CT/CT-CBCT deformable image registration (DIR) techniques. Each scenario was compared to 3D(Ref.) A separate cohort of ten lung SBRT patients was selected to validate DIR techniques. The distance discordance metric (DDM) was implemented per voxel and per patient for tumor and organs at risk (OARs), and the dosimetric impact for CT-CBCT DIR geometric errors was calculated. Main results. Median and interquartile range (IQR) of the dose difference per voxel were 0.05/2.69 Gy and -0.12/2.68 Gy for 3DAcc-3DRef 4DAcc-3DRef. 4DRef-3DRef
  • Autores: Shettar, M. U.; Rudraiah, M.; Bragard Monier, Jean; et al.
    Revista: ENERGIES
    ISSN: 1996-1073 Vol.16 N° 5 2023 págs. 2365
    The present article investigates viscous fluid flow's heat and mass transfers over a stretching/shrinking sheet using the single and multi-wall carbon nanotube models. The analysis considers the effects of thermal radiation, induced slip, mass transpiration, and inclined magnetic force. The effect of the carbon nanotube model on fluid flow has not been considered in previous studies. By exploiting the similarity variable, the governing nonlinear partial differential equations are converted into nonlinear ordinary differential equation. The derived equations are solved analytically, and we obtained an exact solution for the velocity and energy conservation equation. The physical parameters of interest such as induced slip parameter, suction/injection, magnetic field, thermal radiation, and shear stress are analyzed and presented graphically. In particular, we show that the fluid flow in a single wall carbon nanotube transfers more energy than the multivalued nanotubes.
  • Autores: Camacho-Gomez, D.; Sorzabal Bellido, Ioritz; Ortiz de Solórzano Aurusa, Carlos; et al.
    Revista: ISCIENCE
    ISSN: 2589-0042 Vol.26 N° 7 2023 págs. 107164
    How cells orchestrate their cellular functions remains a crucial question to unravel how they organize in different patterns. We present a framework based on artificial intelligence to advance the understanding of how cell functions are coordinated spatially and temporally in biological systems. It consists of a hybrid physics-based model that integrates both mechanical interactions and cell functions with a data-driven model that regulates the cellular decision-making process through a deep learning algorithm trained on image data metrics. To illustrate our approach, we used data from 3D cultures of murine pancreatic ductal adeno-carcinoma cells (PDAC) grown in Matrigel as tumor organoids. Our approach allowed us to find the underlying principles through which cells activate different cell processes to self-organize in different patterns according to the specific microenvironmental conditions. The framework proposed here expands the tools for simulating biological systems at the cellular level, providing a novel perspective to unravel morphogenetic patterns.
  • Autores: Jiménez Sánchez, Daniel; Ariz Galilea, Mikel; De Andrea, Carlos Eduardo; et al.
    ISSN: 0278-0062 Vol.42 N° 10 2023 págs. 3048 - 3058
    Multiplex immunofluorescence is a novel, high-content imaging technique that allows simultaneous in situ labeling of multiple tissue antigens. This technique is of growing relevance in the study of the tumor microenvironment, and the discovery of biomarkers of disease progression or response to immune-based therapies. Given the number of markers and the potential complexity of the spatial interactions involved, the analysis of these images requires the use of machine learning tools that rely for their training on the availability of large image datasets, extremely laborious to annotate. We present Synplex, a computer simulator of multiplexed immunofluorescence images from user-defined parameters: i. cell phenotypes, defined by the level of expression of markers and morphological parameters; ii. cellular neighborhoods based on the spatial association of cell phenotypes; and iii. interactions between cellular neighborhoods. We validate Synplex by generating synthetic tissues that accurately simulate real cancer cohorts with underlying differences in the composition of their tumor microenvironment and show proof-of-principle examples of how Synplex could be used for data augmentation when training machine learning models, and for the in silico selection of clinically relevant biomarkers. Synplex is publicly available at
  • Autores: Urbina Sulbaran, Ruddy Eglee (Autor de correspondencia); González Viñas, Wenceslao
    ISSN: 2470-0045 Vol.108 N° 6 2023 págs. 65107
    We report experimental results on breath figures (BFs) observed on substrates with quenched disorder. The evolution of BFs is found to be primarily influenced by global parameters associated with boundary conditions. We investigate classical statistical measures and explore topological properties using persistent homology techniques based on a modified Vietoris-Rips complex. Our findings reveal that the evolution of the number surface density of condensed droplets plays a crucial role in determining various condensation stages previously considered distinct. This evolution is significantly influenced by the distribution of nucleation sites and the individual growth law governing water droplets when coalescence does not occur. Ultimately, we demonstrate the capability to predict coalescence events based on the topological characteristics of BFs at a given point in time.
  • Autores: Arce, P. (Autor de correspondencia); Lagares, J. I.; Azcona Armendáriz, Juan Diego; et al.
    ISSN: 0969-806X Vol.208 2023 págs. 110891
    Background It is widely accepted that Monte Carlo dose calculations offers a higher precision that the commercially available dose calculation algorithms. This advantage may be especially relevant for lung Stereotactic Body Radiation Therapy (SBRT), as this is a precise technique applied to an area of big inhomogeneity. Purpose We conducted a comparative study to reveal the differences between the doses calculated using the Collapsed Cone Convolution algorithm and the GAMOS/Geant4 Monte Carlo calculation for lung cancer patients treated with Stereotactic Body Radiation Therapy on an Elekta Versa HD linac. Methods For this study a set of ten patient treatments carried out at the Clínica Universidad de Navarra was selected. Theanalysis is based on the comparison of several dosimetric quantities for the Gross Tumor Volume (GTV) and several OrgansAt Risk (OARs), and also a gamma index calculation with distance-to-agreement set to 2 mm and dose difference to 3%, as recommended by ICRU to assess clinical impact. In order to guarantee a small uncertainty in the Monte Carlo calculation of the dosimetric quantities, we studied in detail the validity of different methods that may be used to determine this uncertainty. To compensate for lung movements, a 4D-Cone-beam Computed Tomography (CBCT) was acquired before treatment, whichallowed us to identify eight respiratory phases using a temporal binning. Using commercial MIM software®, we performed a deformable image registration between the eight CT respiration phases to construct the 4D doses. The same procedure was applied for the Treatment Planning System (TPS) dose files and for the Monte Carlo dose files. Results The differences between the two algorithms reveal the known weaknesses of the Collapsed Cone Convolution (CCC) algorithm for the calculation of lateral doses and in regions of large density change. The comparison between the two algorithms for individual phase doses shows differences up to 5% of the GTV D95 or 3¿4 Gy in some OARs, which may have a clinical impact. Nevertheless these differences are reduced for the 4D dose in most quantities under study. Conclusions Comparing the dose calculated with a Collapsed Cone Convolution algorithm with GAMOS/Geant4 for ten patients and eight respiratory phases, we found some differences that could have a clinical impact. When combining the eight temporal phases into a 4D dose using the MIM Deformable Image Registration software, the differences diminished substantially. Our statistical analysis concludes that dose uncertainty in the voxels with a maximum dose below a given percentage guarantees uncertainty in the dosimetric quantities below that figure.
  • Autores: Jiménez Sánchez, Daniel; Ariz Galilea, Mikel; Chang H.; et al.
    ISSN: 1361-8415 Vol.78 2022 págs. 102384
    Understanding the spatial interactions between the elements of the tumor microenvironment -i.e. tumor cells. fibroblasts, immune cells- and how these interactions relate to the diagnosis or prognosis of a tumor is one of the goals of computational pathology. We present NaroNet, a deep learning framework that models the multi-scale tumor microenvironment from multiplex-stained cancer tissue images and provides patient-level interpretable predictions using a seamless end-to-end learning pipeline. Trained only with multiplex-stained tissue images and their corresponding patient-level clinical labels, NaroNet unsupervisedly learns which cell phenotypes, cell neighborhoods, and neighborhood interactions have the highest influence to predict the correct label. To this end, NaroNet incorporates several novel and state-of-the-art deep learning techniques, such as patch-level contrastive learning, multi-level graph embeddings, a novel max-sum pooling operation, or a metric that quantifies the relevance that each microenvironment element has in the individual predictions. We validate NaroNet using synthetic data simulating multiplex-immunostained images where a patient label is artificially associated to the -adjustable- probabilistic incidence of different microenvironment elements. We then apply our model to two sets of images of human cancer tissues: 336 seven-color multiplex-immunostained images from 12 high-grade endometrial cancer patients; and 382 35-plex mass cytometry images from 215 breast cancer patients. In both synthetic and real datasets, NaroNet provides outstanding predictions of relevant clinical information while associating those predictions to the presence of specific microenvironment elements. Keywords: Cellular neighborhoods; Deep learning; Imaging mass cytometry; Interpretable machine learning; Multiplex imaging; Self supervised learning; Spatial biology; Tumor microenvironment; Weakly supervised learning.
  • Autores: Billimoria, K.; Díaz-Fernández, Y. A.; Andresen, E.; et al.
    Revista: METALLOMICS
    ISSN: 1756-5901 Vol.14 N° 12 2022 págs. mfac088
    This paper discusses the feasibility of a novel strategy based on the combination of bioprinting nano-doping technology and laser ablation-inductively coupled plasma time-of-flight mass spectrometry analysis for the preparation and characterization of gelatin-based multi-element calibration standards suitable for quantitative imaging. To achieve this, lanthanide up-conversion nanopArtículos were added to a gelatin matrix to produce the bioprinted calibration standards. The features of this bioprinting approach were compared with manual cryosectioning standard preparation, in terms of throughput, between batch repeatability and elemental signal homogeneity at 5 mu m spatial resolution. By using bioprinting, the between batch variability for three independent standards of the same concentration of Y-89 (range 0-600 mg/kg) was reduced to 5% compared to up to 27% for cryosectioning. On this basis, the relative standard deviation (RSD) obtained between three independent calibration slopes measured within 1 day also reduced from 16% (using cryosectioning) to 5% (using bioprinting), supporting the use of a single standard preparation replicate for each of the concentrations to achieve good calibration performance using bioprinting. This helped reduce the analysis time by approximately 3-fold. With cryosectioning each standard was prepared and sectioned individually, whereas using bio-printing it was possible to have up to six different standards printed simultaneously, reducing the preparation time from approximately 2 h to under 20 min (by approximately 6-fold). The bio-printed calibration standards were found stable for a period of 2 months when stored at ambient temperature and in the dark.
  • Autores: Moscoso-Barrera, W. D. (Autor de correspondencia); Urrestarazu Bolumburu, Elena; Alegre Esteban, Manuel; et al.
    ISSN: 1661-7827 Vol.19 N° 11 2022 págs. 6934
    Obstructive sleep apnea (OSA) is a common sleep disorder characterized by repetitive upper airway obstruction, intermittent hypoxemia, and recurrent awakenings during sleep. The most used treatment for this syndrome is a device that generates a positive airway pressure-Continuous Positive Airway Pressure (CPAP), but it works continuously, whether or not there is apnea. An alternative consists on systems that detect apnea episodes and produce a stimulus that eliminates them. Article focuses on the development of a simple and autonomous processing system for the detection of obstructive sleep apneas, using polysomnography (PSG) signals: electroencephalography (EEG), electromyography (EMG), respiratory effort (RE), respiratory flow (RF), and oxygen saturation (SO2). The system is evaluated using, as a gold standard, 20 PSG tests labeled by sleep experts and it performs two analyses. A first analysis detects awake/sleep stages and is based on the accumulated amplitude in a channel-dependent frequency range, according to the criteria of the American Academy of Sleep Medicine (AASM). The second analysis detects hypopneas and apneas, based on analysis of the breathing cycle and oxygen saturation. The results show a good estimation of sleep events, where for 75% of the cases of patients analyzed it is possible to determine the awake/asleep states with an effectiveness of &gt;92% and apneas and hypopneas with an effectiveness of &gt;55%, through a simple processing system that could be implemented in an electronic device to be used in possible OSA treatments.
  • Autores: Huesa Berral, Carlos; Burguete Mas, Javier; Moreno Jiménez, Marta; et al.
    ISSN: 0031-9155 Vol.66 N° 3 2021 págs. 035025
    The purpose of this study was to devise and evaluate a method to quantify the dosimetric uncertainty produced by the interplay between the movement of multileaf collimator (MLC) and respiratory motion in lung stereotactic body radiation therapy (SBRT). The method calculates the dose distribution for all control points from a dynamic treatment in all respiratory phases. The methodology includes some characteristics of a patient's irregular breathing patterns. It selects, for each control point, the phases with maximum and minimum mean dose over the tumor and their corresponding adjacent phases, whenever necessary. According to this selection, the dose matrices from each control point are summed up to obtain two dose distributions in each phase, which are accumulated in the reference phase subsequently by Deformable Image Registration (DIR). D95 and Dmin,0.035cc were calculated over those accumulated dose distributions for Gross Tumor Volume (GTV), Planning Target Volume (PTV) - based on Internal Target Volume (ITV) approach - and Evaluation Target Volume (ETV), a novel concept that applies to 4D dose accumulation. With the ETV, DIR and interplay uncertainties are separated. The methodology also evaluated how variations in the breathing rate and field size affects the mean dose received by the GTV. The method was applied retrospectively in five patients treated with intensity modulated radiotherapy (IMRT) - minimum area defined by the leaves configuration at any control point was at least 4cm2-. Uncertainties in tumor coverage were small (in most patients, changes on D95 and Dmin,0.035cc were below 2% for GTV and ETV) but significant over- and under- dosages near ETV, which can be accentuated by highly irregular breathing. Uncertainties in mean dose for GTV tended to decrease exponentially with increasing field size and were reduced by an increase of breathing rate. The implementation of this method would be helpful to assess treatment quality in patients with irregular breathing. Furthermore, it could be used to study interplay uncertainties when small field sizes are used.
  • Autores: Bragard Monier, Jean; Camara, O.; Echebarria, B.; et al.
    ISSN: 0300-8932 Vol.74 N° 1 2021 págs. 65 - 71
    Cardiovascular diseases currently have a major social and economic impact, constituting one of the leading causes of mortality and morbidity. Personalized computational models of the heart are demonstrating their usefulness both to help understand the mechanisms underlying cardiac disease, and to optimize their treatment and predict the patient's response. Within this framework, the Spanish Research Network for Cardiac Computational Modelling (VHeart-SN) has been launched. The general objective of the VHeart-SN network is the development of an integrated, modular and multiscale multiphysical computational model of the heart. This general objective is addressed through the following specific objectives: a) to integrate the different numerical methods and models taking into account the specificity of patients; b) to assist in advancing knowledge of the mechanisms associated with cardiac and vascular diseases; and c) to support the application of different personalized therapies. This article presents the current state of cardiac computational modelling and different scientific works conducted by the members of the network to gain greater understanding of the characteristics and usefulness of these models. (C) 2020 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.
  • Autores: Diaz, P.; Pérez, L. M.; Reyes, L. I.; et al.
    ISSN: 0960-0779 Vol.153 N° P1 2021 págs. 111416
    This work presents a study of the Faraday instability in a parametrically forced Fermi-Fermi mixture. The condensate is confined in the transversal spatial dimension with a strong parametric confinement potential and in the longitudinal spatial dimension with a weaker potential. The theoretical description is done using the mean-field theory with two amplitude equations that represent each spin state. In order to stabilize the Faraday patterns, a phenomenological damping term is introduced. The influence of the Zeeman interaction is analyzed in detail. In particular, phase diagrams of the existence and stability of the Faraday waves are calculated as a function of the Zeeman interaction, the coupling parameter, and the forcing amplitude. The degree of segregation of the two fields and their synchronization level is also calculated as a function of the Zeeman parameter. In addition, we examine how the pattern wavelength varies as a function of the Zeeman parameter and the forcing frequency
  • Autores: Urbina Sulbaran, Ruddy Eglee; Lefavrais, S.; Royon, L.; et al.
    ISSN: 0022-1694 Vol.599 2021 págs. 126263
    Hydrogels are known to adsorb a large amount of vapor and liquid water, making them good candidates to enhance the amount of dew condensed from atmosphere. Although water vapor adsorption and liquid invasion in hydrogels have been the object of many studies, water condensation has been only little investigated. We address here the process of dew condensation on hydrogel grains widely used in agriculture (Aquasorb 3005 (TM)). We show that dew condensing on hydrogels is enhanced when compared to a regular bare substrate due to vapor adsorption, which adds to condensation. Hydrogels, which can both capture water by vapor adsorption and condense water vapor with high efficiency, are thus good candidates to harvest water vapor from atmosphere with higher yield than regular bare surfaces.
  • Autores: Bragard Monier, Jean; Vélez, J. A.; Riquelme, J. A.; et al.
    ISSN: 0031-8949 Vol.96 N° 12 2021 págs. 124045
    We have studied a route of chaos in the dissipative Landau-Lifshitz-Gilbert equation representing the magnetization dynamics of an anisotropic nanoparticle subjected to a time-variant magnetic field. This equation presents interesting chaotic dynamics. In the parameter space, for some forcing frequency and magnetic strength of the applied field, one observes a transition from a regular periodic behavior to chaotic dynamics. The chaotic dynamics, close to the bifurcation, are characterized by type-III intermittency. Long epochs of quasi-regular dynamics followed by turbulent bursts. The characterization of the intermittencies has been done through four different techniques. The first method is associated with the computation of the Lyapunov exponents that characterize the chaotic regime. The second and third methods are associated with the statistics of the duration of the laminar epochs prior to a turbulent burst. The fourth method is associated with the subharmonic instability present in those laminar epochs and quantified through a Poincare section method. At the end of the manuscript, we compare the result obtained by the different techniques and discuss the methods' limitations.
  • Autores: Barberá, M. I. (Autor de correspondencia); Hernández-Verdejo, J. L.; Bragard Monier, Jean; et al.
    ISSN: 2164-2591 Vol.10 N° 13 2021 págs. 26
    Purpose: To measure the in vitro flow properties of the PRESERFLO implant for comparison with the theoretical resistance to flow. Methods: The PRESERFLO was designed to control the flow of aqueous humor according to the Hagen-Poiseuille (HP) equation. Scanning electron microscopy (SEM) was performed to analyze the ultrastructure, and flow measurements were carried out using a gravity-flow setup. Results: SEM images of the PRESERFLO showed luminal diameters of 67.73 x 65.95 mu m and 63.66 x 70.54 mu m. The total diameter was 337.2 mu m, and the wall was 154 mu m wide. The theoretical calculation of the resistance to flow (R) for an aqueous humor (AH) viscosity of 0.7185 centipoises (cP) was 1.3 mm Hg/(mu L/min). Hence, assuming a constant AH flow of 2 mu L/min, the pressure differential across the device (AP) was estimated to be 2.6 mm Hg. The gravity-flow experiment allowed us to measure the experimental resistance to flow, which was R-E = 1.301 mm Hg/(mu L/min), in agreement with the theoretical resistance to flow R given by the HP equation. Conclusions: The experimental and theoretical flow testing showed that the pressure drop across this device would not be large enough to avoid hypotony unless the resistance to outflow of the sub-Tenon space was sufficient to control the intraocular pressure in the early postoperative period. Translational Relevance: The fluid properties of glaucoma subconjunctival drainage devices determine their specific bleb-forming capacity and ability to avoid hypotony and therefore their safety and efficacy profile. Translational Relevance: The fluid properties of glaucoma subconjunctival drainage devices determine their specific bleb-forming capacity and ability to avoid hypotony and therefore their safety and efficacy profile.
  • Autores: Azcona Armendáriz, Juan Diego; Aguilar Redondo, Pedro Borja; Irazola Rosales, Leticia; et al.
    ISSN: 0167-8140 Vol.161 N° Supl. 1 2021 págs. S1422 - S1423
  • Autores: Azcona Armendáriz, Juan Diego; Aguilar Redondo, Pedro Borja; Viñals Muñoz, Alberto; et al.
    ISSN: 0167-8140 Vol.161 N° Supl. 1 2021 págs. S1350 - S1351
  • Autores: Huesa Berral, Carlos; Juan-Cruz, C.; Van Kranen, S.; et al.
    ISSN: 0167-8140 Vol.161 N° S1 2021 págs. S1258 - S1259
    Respiratory motion and interfractional anatomical variations are sources of geometric uncertainty in lung stereotactic body radiation therapy (SBRT). The purpose of this study was to evaluate the separate and combined effects of respiratory motion and interfractional anatomical variations during the course of SBRT treatment.
  • Autores: Azcona Armendáriz, Juan Diego; Aguilar Redondo, Pedro Borja; Viñals Muñoz, Alberto; et al.
    ISSN: 0167-8140 Vol.161 N° Supl. 1 2021 págs. S1451 - S1452
  • Autores: Rato Mendes, P.; Arce, P.; Lagares, J. I.; et al.
    ISSN: 0167-8140 Vol.161 N° Supl. 1 2021 págs. S1286
  • Autores: Arce, P. (Autor de correspondencia); Lagares, J. I.; Azcona Armendáriz, Juan Diego; et al.
    ISSN: 0168-9002 Vol.964 2020 págs. 163755
    We have studied each of the physics options that Geant4 offers to simulate an X-ray radiotherapy treatment with the aim of obtaining those that provide the best possible match to the experimental data of dose profiles and at the same time reduce the CPU time. The procedure has been repeated for two linac setups: an ELEKTA Versa HD with an Agility Multileaf Collimator using two nominal energies, 6 MV and 10 MV, both without flattening filter. After combining the results with those of a previous similar study of a 6 MV VARIAN Clinac 2100 C/D linac with flattening filter, we can propose a set of optimized Geant4 physics options of general use for radiotherapy simulation. Together with this, we have optimized the CPU time using several of the optimization techniques that GAMOS offers, reaching a reduction of several hundred times for each setup.
  • Autores: Velez, J. A.; Bragard Monier, Jean; Perez, L. M. (Autor de correspondencia); et al.
    Revista: CHAOS (EEUU)
    ISSN: 1054-1500 Vol.30 N° 9 2020 págs. 093112
    In this work, we study numerically the periodicity of regular regions embedded in chaotic states for the case of an anisotropic magnetic particle. The particle is in the monodomain regime and subject to an applied magnetic field that depends on time. The dissipative Landau-Lifshitz-Gilbert equation models the particle. To perform the characterization, we compute several two-dimensional phase diagrams in the parameter space for the Lyapunov exponents and the isospikes. We observe multiple transitions among periodic states, revealing complex topological structures in the parameter space typical of dynamic systems. To show the finer details of the regular structures, iterative zooms are performed. In particular, we find islands of synchronization for the magnetization and the driven field and several shrimp structures with different periods.
  • Autores: Jiménez Sánchez, Daniel; Ariz Galilea, Mikel; Morgado, J. M. ; et al.
    ISSN: 1367-4803 Vol.36 N° 5 2020 págs. 1590 - 1598
    Motivation: Recent advances in multiplex immunostaining and multispectral cytometry have opened the door to simultaneously visualizing an unprecedented number of biomarkers both in liquid and solid samples. Properly unmixing fluorescent emissions is a challenging task, which normally requires the characterization of the individual fluorochromes from control samples. As the number of fluorochromes increases, the cost in time and use of reagents becomes prohibitively high. Here, we present a fully unsupervised blind spectral unmixing method for the separation of fluorescent emissions in highly mixed spectral data, without the need for control samples. To this end, we extend an existing method based on non-negative Matrix Factorization, and introduce several critical improvements: initialization based on the theoretical spectra, automated selection of 'sparse' data and use of a re-initialized multilayer optimizer. Results: Our algorithm is exhaustively tested using synthetic data to study its robustness against different levels of colocalization, signal to noise ratio, spectral resolution and the effect of errors in the initialization of the algorithm. Then, we compare the performance of our method to that of traditional spectral unmixing algorithms using novel multispectral flow and image cytometry systems. In all cases, we show that our blind unmixing algorithm performs robust unmixing of highly spatially and spectrally mixed data with an unprecedently low computational cost. In summary, we present the first use of a blind unmixing method in multispectral flow and image cytometry, opening the door to the widespread use of our method to efficiently pre-process multiplex immunostaining samples without the need of experimental controls.
  • Autores: Hawks Gutiérrez, Claudia Elizabeth; Elorza Barbajero, Jorge; Wittt, A.; et al.
    ISSN: 0218-1274 Vol.29 N° 8 2019 págs. 1930021
    Connexins are specialized ionic channels that control the action potential propagation between cardiac myocytes. In this paper, we study the connexin dynamics in a one-dimensional model of cardiac tissue. We show that the connexin dynamics may lead to a spatial organization of the gap junction conductance. In the numerical simulations presented in this paper we have found two different regimes for the spatial organization of the conductances: (a) a spatially uniform conductance; (b) a spatially complex pattern of local values of high and low conductances. in addition, we have observed that, locally, the two final states are limit cycles with a period equal to the period associated with the external excitation of the tissue strand. The conductance dispersion usually takes place on a very large time scale, i.e. thousands of heart beats, and on a very short spatial scale. Due to its simplicity, the one-dimensional setting allows a detailed study of the emerging structure and in particular very long simulations. We have studied the transition between the two aforementioned states as a function of the gap junction conductance characteristics. Furthermore, we have studied the effect of initially added noises on the outcome of the system. Finally, using spatial autocorrelation functions we have characterized the spatial dispersion in conductance values.
  • Autores: Martin-Martin, G. (Autor de correspondencia); Aguilar Redondo, Pedro Borja; Barbes Fernandez, Benigno; et al.
    ISSN: 1724-191X Vol.67 2019 págs. 176 - 184
    Purpose: To investigate ion recombination correction and polarity effects in four ion chamber models in flattening-filter-free (FFF) beams to (1) evaluate their suitability for reference dosimetry; (2) assess the accuracy of the two-voltage technique (TVA) against the Bruggmoser formalism; and (3) examine the influence of the accelerator type on the recombination correction. Methods: Jaffe plots were created for a variety of microchambers, small-volume and Farmer-type chambers to obtain k(s), the recombination correction factor, using two different types of accelerators. These values were plotted against dose-per-pulse and Jaffe plots for opposite polarities were created to determine which chambers meet the AAPM TG-51 addendum recombination and polarity specifications. Results: Nearly all small-volume chambers exhibited reference-class behavior with respect to ion recombination and polarity effects. The microchambers exhibited anomalous recombination and polarity effects, precluding their use for reference dosimetry in FFF beams. For the reference-class chambers, agreement between TVA-determined k(s) values and Jaffe and Bruggmoser formalisms-determined k(s) values was within 0.1%. No significant differences were found between the k(s) values obtained with the two different accelerators used in this work. Conclusions: This study stresses the need to characterize ion recombination correction and polarity effects for small-volume chambers and microchambers on an individual..
  • Autores: Rodríguez García, Jesus Oscar; Burguete Mas, Javier
    ISSN: 2470-0045 Vol.99 N° 2 2019 págs. 023111
    The cylindrical wall boundary layer of a closed cylinder split in two halves at the equator is studied experimentally. When these two parts rotate in exact corotation the internal flow is essentially in solid-body rotation at the angular velocity of both halves. When a slight difference between the rotation frequencies is established a secondary flow is created due to the differential rotation between both sides and restricted to the boundary layer. This behavior of the boundary layer is compared with theoretical and numerical results finding the ¿sandwich¿ structure of a Stewartson boundary layer. Time-dependent waves are observed near the cylindrical wall. Their behavior for different values of the control parameters are presented. Finally, a global recirculation mode is also found due to a symmetry-breaking induced between sides that appears because of a slight misalignment of the experimental setup, whose characteristics are compatible with the behavior of a precessing cylinder.
  • Autores: Muhammad Aslam, Raheema; González Viñas, Wenceslao (Autor de correspondencia)
    ISSN: 0022-3727 Vol.52 N° 34 2019 págs. 344001
    We report experimental results on the patterns that are formed during spin-coating of magnetic colloids at moderate concentrations and compare them with results obtained in diluted colloids. We show that, for moderate concentrations, the magnetic interaction between the (ferro)magnetic particles and with the external field is strong enough to overcome the centrifugal force. We study two different configurations for the magnetic field. The first one consists on an axial uniform field, where we obtain spikes perpendicular to the substrate with a well defined order which decreases as rotation rate increases. The second one consists on a radial non-uniform field, where we obtain elongated deposits radially disposed on the substrate. The effect of magnetic fields at moderate concentrations on the effective viscosity is confirmed to be much more important in the case of a uniform magnetic field, by increasing the hydrodynamic time-scale which gives the ferromagnetic particles enough time to strongly interact to form the spikes.
  • Autores: Azcona Armendáriz, Juan Diego (Autor de correspondencia); Huesa Berral, Carlos; Moreno Jiménez, Marta; et al.
    ISSN: 0094-2405 Vol.46 N° 10 2019 págs. 4346 - 4355
    Purpose To use four-dimensional (4D) dose accumulation based on deformable image registration (DIR) to assess dosimetric uncertainty in lung stereotactic body radiation therapy (SBRT) treatment planning. A novel concept, the Evaluation Target Volume (ETV), was introduced to achieve this goal. Methods The internal target volume (ITV) approach was used for treatment planning for 11 patients receiving lung SBRT. Retrospectively, 4D dose calculation was done in Pinnacle v9.10. Total dose was accumulated in the reference phase using DIR with MIM. DIR was validated using landmarks introduced by an expert radiation oncologist. The 4D and three-dimensional (3D) dose distributions were compared within the gross tumor volume (GTV) and the planning target volume (PTV) using the D-95 and D-min (calculated as D-min,D-0.035cc) metrics. For lung involvement, the mean dose and V-20, V-10, and V-5 were used in the 3D to 4D dose comparison, and D-max (D-0.1cc) was used for all other organs at risk (OAR). The new evaluation target volume (ETV) was calculated by expanding the GTV in the reference phase in order to include geometrical uncertainties of the DIR, interobserver variability in the definition of the tumor, and uncertainties of imaging and delivery systems. D-95 and D-min,D-0.035cc metrics were then calculated on the basis of the ETV for 4D accumulated dose distributions, and these metrics were compared with those calculated from the PTV for 3D planned dose distributions.
  • Autores: Cortes Domínguez, Iván; Fernández Seara, María Asunción; Pérez Fernández, Nicolás; et al.
    ISSN: 2076-3417 Vol.9 N° 22 2019 págs. 4904
    We present a novel method to characterize the morphology of semicircular canals of the inner ear. Previous experimental works have a common nexus, the human-operator subjectivity. Although these methods are mostly automatic, they rely on a human decision to determine some particular anatomical positions. We implement a systematic analysis where there is no human subjectivity. Our approach is based on a specific magnetic resonance study done in a group of 20 volunteers. From the raw data, the proposed method defines the centerline of all three semicircular canals through a skeletonization process and computes the angle of the functional pair and other geometrical parameters. This approach allows us to assess the inter-operator effect on other methods. From our results, we conclude that, although an average geometry can be defined, the inner ear anatomy cannot be reduced to a single geometry as seen in previous experimental works. We observed a relevant variability of the geometrical parameters in our cohort of volunteers that hinders this usual simplification.
  • Autores: Cortes Domínguez, Iván (Autor de correspondencia); Burguete Mas, Javier
    Revista: CHAOS (EEUU)
    ISSN: 1054-1500 Vol.28 N° 7 2018 págs. 075514
    The main objective of this work is the study and analysis of non-linearities forced through oscillating magnetic fields in a conducting fluid where the instabilities are triggered due to magnetohydrodynamic forces. Different geometries have been studied and different surface patterns that break the symmetries have been observed. First, an InGaSn drop of fluid where the system breaks the azimuthal and radial symmetries depending on the volume is observed. Second, we extend the study to an InGaSn annular configuration where the presence of patterns opens the door to discuss the possibility to extend these results to other configurations as biological systems, where the conducting fluid is an electrolyte. This configuration has an added interest, as it has been proposed that the vertigoes triggered on patients in an MRI test could be generated by the interaction of the magnetic field with the electrolyte present in the inner ear.
  • Autores: Baghramyan, H. M. (Autor de correspondencia); Barseghyan, M. G.; Kirakosyan, A. A.; et al.
    ISSN: 2045-2322 Vol.8 N° 6145 2018
    The rendering of different shapes of just a single sample of a concentric double quantum ring is demonstrated realizable with a terahertz laser field, that in turn, allows the manipulation of electronic and optical properties of a sample. It is shown that by changing the intensity or frequency of laser field, one can come to a new set of degenerated levels in double quantum rings and switch the charge distribution between the rings. In addition, depending on the direction of an additional static electric field, the linear and quadratic quantum confined Stark effects are observed. The absorption spectrum shifts and the additive absorption coefficient variations affected by laser and electric fields are discussed. Finally, anisotropic electronic and optical properties of isotropic concentric double quantum rings are modeled with the help of terahertz laser field.
  • Autores: Giraldo-Cadavid, L. F.; Burguete Mas, Javier; Rueda, F.; et al.
    Revista: DYSPHAGIA
    ISSN: 0179-051X Vol.33 N° 1 2018 págs. 15 - 25
    Recent studies have shown an association between alterations in laryngopharyngeal mechanosensitivity (LPMS) and dysphagia, obstructive sleep apnea, and chronic cough hypersensitivity syndrome. A previous reliability study of a new laryngopharyngeal endoscopic esthesiometer and rangefinder (LPEER) showed high intra- and inter-rater reliability; however, its accuracy has not been tested. We performed an accuracy study of the LPEER in a prospectively and consecutively recruited cohort of 118 patients at two tertiary care university hospitals. Most of the patients were suffering from dysphagia, and all of them underwent a standard clinical evaluation and fiberoptic endoscopic evaluation of swallowing with sensory testing (FEESST) using a new sensory testing protocol. The sensory test included determinations of the laryngeal adductor reflex threshold (LART), the cough reflex threshold (CRT) and the gag reflex threshold (GRT). Abnormalities on these reflex thresholds were evaluated for associations with major alterations in swallowing safety (pharyngeal residues, penetration, and aspiration). We evaluated the discriminative capacity of the LPMS test using ROC curves and the area under the curve (AUC-ROC) and its relationship with the eight-point penetration-aspiration scale (PAS) using the Spearman's ¿ correlation coefficient (SCC). We found a positive correlation between the PAS and LART (SCC 0.47; P < 0.001), CRT (SCC 0.46; P < 0.001) and GRT (SCC 0.34; P = 0.002). The AUC-ROC values for detecting a PAS ¿7 were as follows: LART, 0.83 (P < 0.0001); CRT, 0.79 (P < 0.0001); GRT, 0.72 (P < 0.0001). In this study, the LPEER showed good accuracy for evaluating LPMS. These results justify further validation studies in independent populations.
  • Autores: Jablonska, Paola Anna; Gimeno Morales, Marta; Arbea Moreno, Leire; et al.
    ISSN: 1522-8517 Vol.20 N° Supl. 3 2018 págs. 251 - 252
  • Autores: Cambeiro Vázquez, Felix Mauricio; Díez-Caballero Alonso, Fernando José; Gimeno Morales, Marta; et al.
    ISSN: 0167-8140 Vol.127 N° Supl. 1 2018 págs. S129 - S129
  • Autores: Jablonska, Paola Anna; Gimeno Morales, Marta; García-Consuegra López-Picazo, Alejandro; et al.
    ISSN: 1522-8517 Vol.20 2018 págs. 253 - 253
  • Autores: Azcona Armendáriz, Juan Diego; Moreno Jiménez, Marta; Huesa Berral, Carlos; et al.
    ISSN: 0094-2405 Vol.45 N° 6 2018 págs. E523 - E524
  • Autores: Giraldo-Cadavid, L. F. ; Fernández González, Secundino; Burguete Mas, Javier; et al.
    ISSN: 0903-1936 Vol.52 N° Supl. 62 2018
  • Autores: Martin-Martin, G.; Aguilar Redondo, Pedro Borja; Barbes Fernandez, Benigno; et al.
    ISSN: 0167-8140 Vol.127 N° Supl.1 2018 págs. S461 - S462

Proyectos desde 2018

  • Título: Criticalidad pasiva mediada por materia activa y viva
    Código de expediente: PID2021-129066NA-I00
    Investigador principal: REINALDO GARCIA GARCIA.
    Convocatoria: 2021 AEI Proyectos de Generación del Conocimiento
    Fecha de inicio: 01-09-2022
    Fecha fin: 31-08-2025
    Importe concedido: 78.650,00€
    Otros fondos: Fondos FEDER
  • Título: Inestabilidades en fluidos fuera del equilibro
    Código de expediente: FIS2017-83401-P
    Convocatoria: 2017 MINECO EXCELENCIA
    Fecha de inicio: 01-01-2018
    Fecha fin: 30-09-2021
    Importe concedido: 54.450,00€
    Otros fondos: Fondos FEDER