Browsing by Author "Hurtado, Daniel E."

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    A machine-learning regional clustering approach to understand ventilator-induced lung injury: a proof-of-concept experimental study
    (2024) Cruces, Pablo; Retamal, Jaime; Damián, Andrés; Lago, Graciela; Blasina, Fernanda; Oviedo, Vanessa; Medina, Tania; Pérez, Agustín; Vaamonde, Lucía; Dapueto, Rosina; González-Dambrauskas, Sebastian; Serra, Alberto; Monteverde-Fernandez, Nicolas; Namías, Mauro; Martínez, Javier; Hurtado, Daniel E.
    Background The spatiotemporal progression and patterns of tissue deformation in ventilator-induced lung injury (VILI) remain understudied. Our aim was to identify lung clusters based on their regional mechanical behavior over space and time in lungs subjected to VILI using machine-learning techniques. Results Ten anesthetized pigs (27±2 kg) were studied. Eight subjects were analyzed. End-inspiratory and endexpiratory lung computed tomography scans were performed at the beginning and after 12 h of one-hit VILI model. Regional image-based biomechanical analysis was used to determine end-expiratory aeration, tidal recruitment, and volumetric strain for both early and late stages. Clustering analysis was performed using principal component analysis and K-Means algorithms. We identifed three diferent clusters of lung tissue: Stable, Recruitable Unstable, and Non-Recruitable Unstable. End-expiratory aeration, tidal recruitment, and volumetric strain were signifcantly diferent between clusters at early stage. At late stage, we found a step loss of end-expiratory aeration among clusters, lowest in Stable, followed by Unstable Recruitable, and highest in the Unstable Non-Recruitable cluster. Volumetric strain remaining unchanged in the Stable cluster, with slight increases in the Recruitable cluster, and strong reduction in the Unstable Non-Recruitable cluster. Conclusions VILI is a regional and dynamic phenomenon. Using unbiased machine-learning techniques we can identify the coexistence of three functional lung tissue compartments with diferent spatiotemporal regional biomechanical behavior.
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    Accelerating cardiac and vessel mechanics simulations: An energy-transform variational formulation for soft-tissue hyperelasticity
    (2021) Hurtado, Daniel E.; Zavala, Patricio
    Computational modeling constitutes a powerful tool to understand the biomechanical function of the heart and the aorta. However, the high dimensionality and non-linear nature of current models can be challenging in terms of computational demands. In this work, we present a novel energy-transform variational formulation (ETVF) for accelerating the numerical simulation of hyperelastic biosolids. To this end, we propose a mixed variational framework, where we introduce auxiliary fields that render the strain energy density into a quadratic form, at the expense of adding unknown fields to the problem. We further reduce the non-linearity of the problem by transforming the constraints that arise due to auxiliary fields in a Lagrange multiplier formulation. The resulting continuous problem is solved by using multi-field non-linear finite-element schemes. We assess the numerical performance of the ETVF by solving two benchmark problems in cardiac and vessel mechanics and one anatomically-detailed model of a human heart under passive filling that assumes an orthotropic heterogeneous constitutive relation. Our results show that the ETVF can deliver speed-ups up to 2.28x in realistic cardiovascular simulations only by considering the proposed reformulation of the hyperelastic problem. Further, we show that the ETVF can decrease the wall-clock time of simulations solved in parallel architectures (8-cores) by 55%. We argue that the decrease in computational cost is explained by the ability of the ETVF to reduce the condition number of tangent operators. We believe that the ETVF offers an effective framework to accelerate the numerical solution of general hyperelastic problems, enabling the solution of large-scale problems in attractive computing times. Codes are available for download at https://github.com/dehurtado/ETVF. (C) 2021 Elsevier B.V. All rights reserved.
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    Adaptive Mesh Refinement in Deformable Image Registration: A Posteriori Error Estimates for Primal and Mixed Formulations
    (2021) Barnafi, Nicolas; Gatica, Gabriel N.; Hurtado, Daniel E.; Miranda, Willian; Ruiz-Baier, Ricardo
    Deformable image registration (DIR) is a popular technique for the alignment of digital images, with highly relevant applications in medical image analysis. However, the numerical solution of DIR problems can be very challenging in computational terms, as the improvement of the DIR solution typically involves a uniform refinement of the underlying domain discretization that exponentially increases the number of degrees of freedom. In this work, we develop adaptive mesh refinement schemes particularly designed for the finite-element solution of DIR problems. We start by deriving residual-based a posteriori error estimators for the primal and mixed formulations of the DIR problem and show that they are reliable and efficient. Based on these error estimators, we implement adaptive mesh-refinement schemes into a finite-element code to register images. We assess the numerical performance of the proposed adaptive scheme on smooth synthetic images, where numerical convergence is verified. We further show that the adaptive mesh refinement scheme can deliver solutions to DIR problems with significant reductions in the number of degrees of freedom without compromising the accuracy of the solution. We also confirm that the adaptive scheme proposed for the mixed DIR formulation successfully handles volume-constrained registration problems, providing optimal convergence in analytic examples. To demonstrate the applicability of the method, we perform adaptive DIR on medical brain images and binary images and study how image noise affects the proposed refinement schemes.
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    Computational modeling of capillary perfusion and gas exchange in alveolar tissue
    (2022) Zurita, Pablo; Hurtado, Daniel E.
    Gas exchange is an essential function of the respiratory system that couples fundamentally with perfusion in respiratory alveoli. Current mathematical formulations and computational models of these two phenomena rely on one-dimensional approximations that neglect the intricate volumetric microstructure of alveolar structures. In this work, we introduce a coupled three-dimensional computational model of pulmonary capillary perfusion and gas exchange that conforms to alveolar morphology. To this end, we derive non-linear partial differential equations and boundary conditions from physical principles that govern the behavior of blood and gases in arbitrary alveolar domains. We numerically solve the resulting formulation by proposing and implementing a non-linear finite-element scheme. Further, we carry out several numerical experiments to validate our model against one-dimensional simulations and demonstrate its applicability to morphologically-inspired geometries. Numerical simulations show that our model predicts blood pressure drops and blood velocities expected in the pulmonary capillaries. Moreover, we replicate partial pressure dynamics of oxygen and carbon dioxide reported in previous studies. This overall behavior is also observed in three-dimensional alveolar geometries, providing more detail associated with the spatial distribution of fields of interest and the influence of the shape of the domain. We envision that this model opens the door for enhanced in silico studies of gas exchange and perfusion on realistic geometries, coupled models of respiratory mechanics and gas exchange, and multi-scale analysis of lung function; furthering our understanding of lung physiology and pathology. Codes are available at https://github.com/comp-medicine-uc/num-model-alv-perfusion-gas-exchange. (c) 2022 Elsevier B.V. All rights reserved.
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    Determination of the Respiratory Compensation Point by Detecting Changes in Intercostal Muscles Oxygenation by Using Near-Infrared Spectroscopy
    (MDPI, 2022) Contreras Briceño, Felipe; Espinosa Ramírez, Maximiliano; Keim Bagnara, Vicente; Carreño Roman, Matías Ignacio; Rodríguez Villagra, Rafael Alejandro; Villegas Belmar, Fernanda; Viscor, Gines; Gabrielli Nervi, Luigi Arnaldo; Andia, Marcelo E.; Araneda, Oscar F.; Hurtado, Daniel E.
    This study aimed to evaluate if the changes in oxygen saturation levels at intercostal muscles (SmO2 m.intercostales) assessed by near-infrared spectroscopy (NIRS) using a wearable device could determine the respiratory compensation point (RCP) during exercise. Fifteen healthy competitive triathletes (eight males; 29 +/- 6 years; height 167.6 +/- 25.6 cm; weight 69.2 +/- 9.4 kg; (V) over dotO(2)-max 58.4 +/- 8.1 mL.kg(-1).min(-1)) were evaluated in a cycle ergometer during the maximal oxygen-uptake test ((V) over dotO(2)-max), while lung ventilation ((V) over dotE), power output (watts, W) and SmO2 mantercostales were measured. RCP was determined by visual method (RCPvisual : changes at ventilatory equivalents ((V) over dotE.CO2-1, (V) over dotE.(V) over dotO(2)(-1)) and end-tidal respiratory pressure (PetO(2), PetCO(2)) and NIRS method (RCP NIRS : breakpoint of fall in SmO2 m.intercostales). During exercise, SmO2 m.intercostales decreased continuously showing a higher decrease when (V) over dotE increased abruptly. A good agreement between methods used to determine RCP was found (visual vs NIRS) at %(V) over dotO(2)-max, (V) over dotO(2), (V) over dotE, and W (Bland-Altman test). Correlations were found to each parameters analyzed (r = 0.854; r = 0.865; r = 0.981; and r = 0,968; respectively. p < 0.001 in all variables, Pearson test), with no differences (p < 0.001 in all variables, Student's t-test) between methods used (RCPvisual and RCPNIRS). We concluded that changes at SmO2 m.intercostales measured by NIRS could adequately determine RCP in triathletes.
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    Distribution and Magnitude of Regional Volumetric Lung Strain and Its Modification by PEEP in Healthy Anesthetized and Mechanically Ventilated Dogs
    (2022) Araos, Joaquin; Cruces, Pablo; Martin-Flores, Manuel; Donati, Pablo; Gleed, Robin D.; Boullhesen-Williams, Tomas; Perez, Agustin; Staffieri, Francesco; Retamal, Jaime; Melo, Marcos Vidal F.; Hurtado, Daniel E.
    The present study describes the magnitude and spatial distribution of lung strain in healthy anesthetized, mechanically ventilated dogs with and without positive end-expiratory pressure (PEEP). Total lung strain (LSTOTAL) has a dynamic (LSDYNAMIC) and a static (LSSTATIC) component. Due to lung heterogeneity, global lung strain may not accurately represent regional total tissue lung strain (TSTOTAL), which may also be described by a regional dynamic (TSDYNAMIC) and static (TSSTATIC) component. Six healthy anesthetized beagles (12.4 +/- 1.4 kg body weight) were placed in dorsal recumbency and ventilated with a tidal volume of 15 ml/kg, respiratory rate of 15 bpm, and zero end-expiratory pressure (ZEEP). Respiratory system mechanics and full thoracic end-expiratory and end-inspiratory CT scan images were obtained at ZEEP. Thereafter, a PEEP of 5 cmH(2)O was set and respiratory system mechanics measurements and end-expiratory and end-inspiratory images were repeated. Computed lung volumes from CT scans were used to evaluate the global LSTOTAL, LSDYNAMIC, and LSSTATIC during PEEP. During ZEEP, LSSTATIC was assumed zero; therefore, LSTOTAL was the same as LSDYNAMIC. Image segmentation was applied to CT images to obtain maps of regional TSTOTAL, TSDYNAMIC, and TSSTATIC during PEEP, and TSDYNAMIC during ZEEP. Compliance increased (p = 0.013) and driving pressure decreased (p = 0.043) during PEEP. PEEP increased the end-expiratory lung volume (p < 0.001) and significantly reduced global LSDYNAMIC (33.4 +/- 6.4% during ZEEP, 24.0 +/- 4.6% during PEEP, p = 0.032). LSSTATIC by PEEP was larger than the reduction in LSDYNAMIC; therefore, LSTOTAL at PEEP was larger than LSDYNAMIC at ZEEP (p = 0.005). There was marked topographic heterogeneity of regional strains. PEEP induced a significant reduction in TSDYNAMIC in all lung regions (p < 0.05). Similar to global findings, PEEP-induced TSSTATIC was larger than the reduction in TSDYNAMIC; therefore, PEEP-induced TSTOTAL was larger than TSDYNAMIC at ZEEP. In conclusion, PEEP reduced both global and regional estimates of dynamic strain, but induced a large static strain. Given that lung injury has been mostly associated with tidal deformation, limiting dynamic strain may be an important clinical target in healthy and diseased lungs, but this requires further study.
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    Evaluation of Lung Aeration and Respiratory System Mechanics in Obese Dogs Ventilated With Tidal Volumes Based on Ideal vs. Current Body Weight
    (2021) Araos, Joaquin; Lacitignola, Luca; de Monte, Valentina; Stabile, Marzia; Porter, Ian; Hurtado, Daniel E.; Perez, Agustin; Crovace, Antonio; Grasso, Salvatore; Martin-Flores, Manuel; Staffieri, Francesco
    We describe the respiratory mechanics and lung aeration in anesthetized obese dogs ventilated with tidal volumes (VT) based on ideal (VTi) vs. current (VTc) body weight. Six dogs with body condition scores >= 8/9 were included. End-expiratory respiratory mechanics and end-expiratory CT-scan were obtained at baseline for each dog. Thereafter, dogs were ventilated with VT 15 ml kg(-1) based on VTi and VTc, applied randomly. Respiratory mechanics and CT-scan were repeated at end-inspiration during VTi and VTc. Data analyzed with linear mixed models and reported as mean +/- SD or median [range]. Statistical significance p < 0.05. The elastance of the lung, chest wall and respiratory system indexed by ideal body weight (IBW) were positively correlated with body fat percentage, whereas the functional residual capacity indexed by IBW was negatively correlated with body fat percentage. At end-expiration, aeration (%) was: hyperaeration 0.03 [0.00-3.35], normoaeration 69.7 [44.6-82.2], hypoaeration 29.3 [13.6-49.4] and nonaeration (1.06% [0.37-6.02]). Next to the diaphragm, normoaeration dropped to 12 +/- 11% and hypoaeration increased to 90 +/- 8%. No differences in aeration between groups were found at end-inspiration. Airway driving pressure (cm H2O) was higher (p = 0.002) during VTc (9.8 +/- 0.7) compared with VTi (7.6 +/- 0.4). Lung strain was higher (p = 0.014) during VTc (55 +/- 21%) than VTi (38 +/- 10%). The stress index was higher (p = 0.012) during VTc (SI = 1.07 [0.14]) compared with VTi (SI = 0.93 [0.18]). This study indicates that body fat percentage influences the magnitude of lung, chest wall, and total respiratory system elastance and resistance, as well as functional residual capacity. Further, these results indicate that obese dogs have extensive areas of hypoaerated lungs, especially in caudodorsal regions. Finally, lung strain and airway driving pressure, surrogates of lung deformation, are higher during VTc than during VTi, suggesting that in obese anesthetized dogs, ventilation protocols based on IBW may be advantageous.
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    Fluid flow migration, rock stress and deformation due to a crustal fault slip in a geothermal system: A poro-elasto-plastic perspective
    (2023) Saez-Leiva, Felipe; Hurtado, Daniel E.; Gerbault, Muriel; Ruz-Ginouves, Javiera; Iturrieta, Pablo; Cembrano, Jose
    Geothermal systems are commonly genetically and spatially associated with volcanic complexes, which in turn, are located nearby crustal fault systems. Faults can alter fluid flow in their surroundings, potentially acting as barriers or conduits for fluids, depending on their architecture and slip-rate. However, this fundamental control on fluid migration is still poorly constrained. Most previous modeling efforts on volcanic and hydrothermal processes consider either only fluid flow in their formulations, or only a mechanical approach, and seldom a full, monolithic coupling between both. In this work, we present a poro-elasto-plastic Finite Element Method (FEM) to address the first-order, time-dependent control that a strike-slip crustal fault exerts on a nearby geothermal reservoir. For the model setting, we selected the Planchon-Peteroa geothermal system in the Southern Andes Volcanic Zone (SAVZ), for which the geometry and kinematics of a potentially seismogenic fault and fluid reservoir is constrained from previous geological and geophysical studies. We assess the emergence and diffusion of fluid pressure domains due to fault slip, as well as the development of tensile/dilational and compressive/contractional domains in the fault' surroundings. Mean stress and volumetric strain magnitudes in these domains range between +/- 1 [MPa] and +/- 10-4 [-], respectively. Our results show the appearance of negative and positive fluid pressure domains in these dilational and contractional regions, respectively. We also investigate the spatial and temporal evolution of such domains resulting from changes in fault permeability and shear modulus, fluid viscosity, and rock rheology. These variations in fluid pressure alter the trajectory of the reservoir fluids, increasing migration to the eastern half of the fault, reaching a maximum fluid flux of 8 to 70 times the stationary flux. Pressure-driven fluid diffusion over time causes fluid flow to return to the stationary state between weeks to months after fault slip. These results suggest that the mechanism that exerts a first-order control is similar to a suction pump, whose duration heavily depends on fault permeability and fluid viscosity. We also show how a von Mises plasticity criterion locally enhances fluid flow. The transient process analyzed in this work highlights the importance of addressing the solid-fluid coupling in numerical models for volcano-tectonic studies.(c) 2023 Elsevier B.V. All rights reserved.
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    Fully Three-Dimensional Hemodynamic Characterization of Altered Blood Flow in Bicuspid Aortic Valve Patients With Respect to Aortic Dilatation: A Finite Element Approach
    (2022) Sotelo, Julio; Franco, Pamela; Guala, Andrea; Dux-Santoy, Lydia; Ruiz-Munoz, Aroa; Evangelista, Arturo; Mella, Hernan; Mura, Joaquin; Hurtado, Daniel E.; Rodriguez-Palomares, Jose F.; Uribe, Sergio
    Background and PurposePrognostic models based on cardiovascular hemodynamic parameters may bring new information for an early assessment of patients with bicuspid aortic valve (BAV), playing a key role in reducing the long-term risk of cardiovascular events. This work quantifies several three-dimensional hemodynamic parameters in different patients with BAV and ranks their relationships with aortic diameter. Materials and MethodsUsing 4D-flow CMR data of 74 patients with BAV (49 right-left and 25 right-non-coronary) and 48 healthy volunteers, aortic 3D maps of seventeen 17 different hemodynamic parameters were quantified along the thoracic aorta. Patients with BAV were divided into two morphotype categories, BAV-Non-AAoD (where we include 18 non-dilated patients and 7 root-dilated patients) and BAV-AAoD (where we include the 49 patients with dilatation of the ascending aorta). Differences between volunteers and patients were evaluated using MANOVA with Pillai's trace statistic, Mann-Whitney U test, ROC curves, and minimum redundancy maximum relevance algorithm. Spearman's correlation was used to correlate the dilation with each hemodynamic parameter. ResultsThe flow eccentricity, backward velocity, velocity angle, regurgitation fraction, circumferential wall shear stress, axial vorticity, and axial circulation allowed to discriminate between volunteers and patients with BAV, even in the absence of dilation. In patients with BAV, the diameter presented a strong correlation (> |+/-0.7|) with the forward velocity and velocity angle, and a good correlation (> |+/-0.5|) with regurgitation fraction, wall shear stress, wall shear stress axial, and vorticity, also for morphotypes and phenotypes, some of them are correlated with the diameter. The velocity angle proved to be an excellent biomarker in the differentiation between volunteers and patients with BAV, BAV morphotypes, and BAV phenotypes, with an area under the curve bigger than 0.90, and higher predictor important scores. ConclusionsThrough the application of a novel 3D quantification method, hemodynamic parameters related to flow direction, such as flow eccentricity, velocity angle, and regurgitation fraction, presented the best relationships with a local diameter and effectively differentiated patients with BAV from healthy volunteers.
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    In-silico study of the cardiac arrhythmogenic potential of biomaterial injection therapy
    (2020) Ramirez, William A.; Gizzi, Alessio; Sack, Kevin L.; Guccione, Julius M.; Hurtado, Daniel E.
    Biomaterial injection is a novel therapy to treat ischemic heart failure (HF) that has shown to reduce remodeling and restore cardiac function in recent preclinical studies. While the effect of biomaterial injection in reducing mechanical wall stress has been recently demonstrated, the influence of biomaterials on the electrical behavior of treated hearts has not been elucidated. In this work, we developed computational models of swine hearts to study the electrophysiological vulnerability associated with biomaterial injection therapy. The propagation of action potentials on realistic biventricular geometries was simulated by numerically solving the monodomain electrophysiology equations on anatomically-detailed models of normal, HF untreated, and HF treated hearts. Heart geometries were constructed from high-resolution magnetic resonance images (MRI) where the healthy, peri-infarcted, infarcted and gel regions were identified, and the orientation of cardiac fibers was informed from diffusion-tensor MRI. Regional restitution properties in each case were evaluated by constructing a probability density function of the action potential duration (APD) at different cycle lengths. A comparative analysis of the ventricular fibrillation (VF) dynamics for every heart was carried out by measuring the number of filaments formed after wave braking. Our results suggest that biomaterial injection therapy does not affect the regional dispersion of repolarization when comparing untreated and treated failing hearts. Further, we found that the treated failing heart is more prone to sustain VF than the normal heart, and is at least as susceptible to sustained VF as the untreated failing heart. Moreover, we show that the main features of VF dynamics in a treated failing heart are not affected by the level of electrical conductivity of the biogel injectates. This work represents a novel proof-of-concept study demonstrating the feasibility of computer simulations of the heart in understanding the arrhythmic behavior in novel therapies for HF.
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    Inelastic Deformable Image Registration (i-DIR): Capturing Sliding Motion through Automatic Detection of Discontinuities
    (2021) Andrade, Carlos I.; Hurtado, Daniel E.
    Deformable image registration (DIR) is an image-analysis method with a broad range of applications in biomedical sciences. Current applications of DIR on computed-tomography (CT) images of the lung and other organs under deformation suffer from large errors and artifacts due to the inability of standard DIR methods to capture sliding between interfaces, as standard transformation models cannot adequately handle discontinuities. In this work, we aim at creating a novel inelastic deformable image registration (i-DIR) method that automatically detects sliding surfaces and that is capable of handling sliding discontinuous motion. Our method relies on the introduction of an inelastic regularization term in the DIR formulation, where sliding is characterized as an inelastic shear strain. We validate the i-DIR by studying synthetic image datasets with strong sliding motion, and compare its results against two other elastic DIR formulations using landmark analysis. Further, we demonstrate the applicability of the i-DIR method to medical CT images by registering lung CT images. Our results show that the i-DIR method delivers accurate estimates of a local lung strain that are similar to fields reported in the literature, and that do not exhibit spurious oscillatory patterns typically observed in elastic DIR methods. We conclude that the i-DIR method automatically locates regions of sliding that arise in the dorsal pleural cavity, delivering significantly smaller errors than traditional elastic DIR methods.
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    Mechanical and morphological characterization of the emphysematous lung tissue
    (2024) Villa, Benjamin; Erranz, Benjamin; Cruces, Pablo; Retamal, Jaime; Hurtado, Daniel E.
    Irreversible alveolar airspace enlargement is the main characteristic of pulmonary emphysema, which has been extensively studied using animal models. While the alterations in lung mechanics associated with these morphological changes have been documented in the literature, the study of the mechanical behavior of parenchymal tissue from emphysematous lungs has been poorly investigated. In this work, we characterize the mechanical and morphological properties of lung tissue in elastase-induced emphysema rat models under varying severity conditions. We analyze the non-linear tissue behavior using suitable hyperelastic constitutive models that enable to compare different non-linear responses in terms of hyperelastic material parameters. We further analyze the effect of the elastase dose on alveolar morphology and tissue material parameters and study their connection with respiratory -system mechanical parameters. Our results show that while the lung mechanical function is not significantly influenced by the elastase treatment, the tissue mechanical behavior and alveolar morphology are markedly affected by it. We further show a strong association between alveolar enlargement and tissue softening, not evidenced by respiratory -system compliance. Our findings highlight the importance of understanding tissue mechanics in emphysematous lungs, as changes in tissue properties could detect the early stages of emphysema remodeling. Statement of significance Gas exchange is vital for life and strongly relies on the mechanical function of the lungs. Pulmonary emphysema is a prevalent respiratory disease where alveolar walls are damaged, causing alveolar enlargement that induces harmful changes in the mechanical response of the lungs. In this work, we study how the mechanical properties of lung tissue change during emphysema. Our results from animal models show that tissue properties are more sensitive to alveolar enlargement due to emphysema than other mechanical properties that describe the function of the whole respiratory system. (c) 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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    Mechanics-informed snakes isogeometric analysis (MISIGA): an image-based method for the estimation of local deformation and strain in blood vessels
    (2022) Cox, Agustin; Ortiz-Puerta, David; Sotelo, Julio; Uribe, Sergio; Hurtado, Daniel E.
    Abnormal deformation of blood vessels has been related to the onset and progression of prevalent cardiovascular diseases. This mechanical connection has motivated the development of computational techniques to assess strain fields in the wall of the aorta from medical images. In this work, we present the mechanics-informed snakes isogeometric analysis (MISIGA) method, which provides seamless 3D estimations of strain fields in the full aorta from magnetic resonance images. Our approach leverages image segmentation formulations with advanced curvilinear representations of irregular vessels to capture the deformation mapping between two configurations captured by image datasets. We further inform this model by describing the motion of the aortic wall based on a Kirchhoff-Love shell approach, which allows us to construct continuous circumferential and longitudinal strain fields in the full aorta. We validate the MISIGA method using synthetically generated images from aortic mechanical simulations, obtaining errors in the strain estimation of 13.2 and 9.8 for the circumferential and longitudinal components. This performance compares favorably with other approaches that are not informed by mechanical considerations. Further, we apply the MISIGA method in the strain assessment of the aorta of a normal subject, which results in longitudinal and circumferential strain values that are in the range of those found in previous studies. We envision that the MISIGA method can open the way to seamless 3D high-fidelity analysis of local strain from medical images of the aorta and other vessels.
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    Modeling pulmonary perfusion and gas exchange in alveolar microstructures
    (2025) Herrera, Bastian; Hurtado, Daniel E.
    Pulmonary capillary perfusion and gas exchange are physiological processes that take place at the alveolar level and that are fundamental to sustaining life. Present-day computational simulations of these phenomena are based on low-dimensional mathematical models solved in idealized alveolar geometries, where the chemical reactions between O-2-CO2 and hemoglobin are simplified. While providing general insights, current modeling efforts fail to capture the complex chemical reactions that take place in pulmonary capillary blood flow on arbitrary geometries and ignore the crucial impact of microstructural morphology on pulmonary function. Here, we propose a coupled continuum perfusion and gas exchange model that captures complex gas and hemoglobin dynamics in realistic geometries of alveolar tissue. To this end, we derive appropriate governing equations incorporating a two-way Hill-like relationship between gas partial pressures and hemoglobin saturations. We numerically solve the resulting boundary-value problem using a non-linear finite-element approach to simulate and validate velocity, partial pressure, and hemoglobin saturation fields in simple geometries. We further perform sensitivity studies to understand the impact of blood speed and acidity variability on key physiological fields. Notably, we simulate perfusion and gas exchange on anatomical alveolar domains constructed from 3D mu-computed-tomography images of murine lungs. Based on these models, we show that morphological variations decrease O-2 and CO2 diffusing capacity, predicting trends and values that are consistent with current medical knowledge. We envision that our model will provide an effective in silico framework to study how exercise and pathological conditions affect perfusion dynamics and the overall gas exchange function of the respiratory system.
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    Morphometric analysis of airways in pre-COPD and mild COPD lungs using continuous surface representations of the bronchial lumen
    (2023) Ortiz-Puerta, David; Diaz, Orlando; Retamal, Jaime; Hurtado, Daniel E.
    Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a prevalent respiratory disease that presents a high rate of underdiagnosis during onset and early stages. Studies have shown that in mild COPD patients, remodeling of the small airways occurs concurrently with morphological changes in the proximal airways. Despite this evidence, the geometrical study of the airway tree from computed tomography (CT) lung images remains underexplored due to poor representations and limited tools to characterize the airway structure.Methods: We perform a comprehensive morphometric study of the proximal airways based on geometrical measures associated with the different airway generations. To this end, we leverage the geometric flexibility of the Snakes IsoGeometric Analysis method to accurately represent and characterize the airway luminal surface and volume informed by CT images of the respiratory tree. Based on this framework, we study the airway geometry of smoking pre-COPD and mild COPD individuals.Results: Our results show a significant difference between groups in airway volume, length, luminal eccentricity, minimum radius, and surface-area-to-volume ratio in the most distal airways.Discussion: Our findings suggest a higher degree of airway narrowing and collapse in COPD patients when compared to pre-COPD patients. We envision that our work has the potential to deliver a comprehensive tool for assessing morphological changes in airway geometry that take place in the early stages of COPD.
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    Multiscale modeling of lung mechanics: From alveolar microstructure to pulmonary function
    (2023) Hurtado, Daniel E.; Aviles-Rojas, Nibaldo; Concha, Felipe
    The mechanical behavior of the lungs has long been associated with the structural properties of alveoli in pulmonary medicine. However, this structure-function relationship has mostly been qualitative, as experimentation in real lungs is costly and limited by ethical standards. Here we present a poromechanical multiscale model that connects key alveolar features with organ-level function. To this end, we first revisit an asymptotic homogenization framework for finite-deformation poromechanics and formulate fine-scale and coarse-scale problems that govern lung mechanics. We further inform the coarse-scale problem using a tetrakaidecahedron micromechanical model for the alveolar response at the fine scale that strongly depends on the alveolar-wall elastic modulus and the initial alveolar porosity. Based on this formulation, we construct a non-linear finite element model from anatomical geometries to simulate the response of human lungs connected to a mechanical ventilator under pressure-controlled and volume-controlled protocols. We show that the predicted signals for airway pressure, airway flow, and lung volume capture the dynamic waveform characteristics observed in human lungs. Further, we demonstrate that lung behavior, measured in terms of respiratory-system compliance, strongly depends on the alveolar-wall elasticity and alveolar porosity. In particular, we show that variations in these microstructural parameters result in marked changes in compliance that follow the structure-function relations observed in lungs with pulmonary fibrosis and emphysema, two prevalent chronic respiratory diseases. We envision that our multiscale lung model can enhance current in silico efforts to experimentation in respiratory research and provide a computational framework for clinically-relevant simulations. Codes are available for download at https://github.com/comp-medicine-uc/multiscale-lung-mechanics.
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    New primal and dual-mixed finite element methods for stable image registration with singular regularization
    (2021) Barnafi, Nicolas; Gatica, Gabriel N.; Hurtado, Daniel E.; Miranda, Willian; Ruiz-Baier, Ricardo
    This work introduces and analyzes new primal and dual-mixed finite element methods for deformable image registration, in which the regularizer has a nontrivial kernel, and constructed under minimal assumptions of the registration model: Lipschitz continuity of the similarity measure and ellipticity of the regularizer on the orthogonal complement of its kernel. The aforementioned singularity of the regularizer suggests to modify the original model by incorporating the additional degrees of freedom arising from its kernel, thus granting ellipticity of the former on the whole solution space. In this way, we are able to prove well-posedness of the resulting extended primal and dual-mixed continuous formulations, as well as of the associated Galerkin schemes. A priori error estimates and corresponding rates of convergence are also established for both discrete methods. Finally, we provide numerical examples confronting our formulations with the standard ones, which prove our finite element methods to be particularly more efficient on the registration of translations and rotations, in addition for the dual-mixed approach to be much more suitable for the quasi-incompressible case, and all the above without losing the flexibility to solve problems arising from more realistic scenarios such as the image registration of the human brain.
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    Noninvasive Continuous Positive Airway Pressure Is a Lung- and Diaphragm-protective Approach in Self-inflicted Lung Injury
    (2024) Cruces, Pablo; Erranz, Benjamín; Pérez, Agustín; Reveco, Sonia; González, Carlos; Retamal, Jaime; Poblete Navarro, Daniela Andrea; Hurtado, Daniel E.; Diaz, Franco
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    Pressure-driven micro-poro-mechanics: A variational framework for modeling the response of porous materials
    (2021) Alvarez-Barrientos, Felipe; Hurtado, Daniel E.; Genet, Martin
    Porous materials are highly relevant in engineering and medical applications due to their enhanced properties and lightweight nature. Current micromechanical models of porous materials can accurately predict the response under the assumptions of small deformations and drained conditions, typically driven by imposed deformations. However, the theoretical framework for the micromechanical modeling of porous material driven by pore pressure in the large deformation range has been understudied. In this work, we develop a finite-deformation variational framework for pressure-driven foams, i.e., materials where the pore pressure in the cavities produces the deformation. We further consider different kinematical constraints in the formulation of boundary conditions: kinematic uniform displacements, periodic displacements and uniform traction. We apply the proposed model in the numerical simulation of lung porous tissue using a spherical alveolar geometry and an image-based geometry obtained from micro computed-tomography images of rat lung. Our results show that the stress distributions in the spherical alveolar model are highly dependent on the kinematical constraints. In contrast, the stress distribution in the image-based alveolar model is not affected by the choice of boundary conditions. Further, when comparing the response of pressure-driven versus deformation-driven models, we conclude that hydrostatic stresses experience a marked shift in their distribution, whereas the deviatoric stresses remain unaffected. Our findings of how stresses are affected by the choice of boundary conditions and geometry take particular relevance in the simulation of the lungs, where the pressure-driven and deformation-driven cases are related to mechanical ventilation and spontaneous breathing.
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    Snakes Isogeometric Analysis (SIGA): Towards accurate and flexible geometrical models of the respiratory airways
    (2022) Ortiz-Puerta, David; Cox, Agustin; Hurtado, Daniel E.
    The construction of accurate patient-specific geometries from medical images is critical to achieving predictive numerical simulations of the respiratory system. However, the generation of surface representations of the airway tree is very challenging due to their complex morphology. In this work, we present a novel framework for creating Non-Uniform Rational B-Splines surface models of the respiratory airways. Our method relies on solving the variational formulation of the Snakes segmentation problem using Isogeometric Analysis (SIGA). We validate the SIGA method by comparing the resulting surface mesh against those delivered by two benchmark surface-fitting methods based on control-point projection. Our results confirm that SIGA outperforms the benchmark methods in creating surface models from computed-tomography images of a normal and a diseased lung. Further, we show that SIGA meshes adapt well to pathological airways with non-convex cross-sections where traditional surface-fitting methods fail. We envision that the geometrical flexibility and accuracy of SIGA will enhance the creation of computational models of the respiratory system under healthy and diseased conditions. (C) 2022 Elsevier B.V. All rights reserved.