Inverse-Consistent Determination of Young\u27s Modulus of Human Lung

Human lung undergoes respiration-induced deformation due to sequential inhalation and exhalation. Accurate determination of lung deformation is crucial for tumor localization and targeted radiotherapy in patients with lung cancer. Numerical modeling of human lung dynamics based on underlying physics and physiology enables simulation and virtual visualization of lung deformation. Dynamical modeling is numerically complicated by the lack of information on lung elastic behavior, structural heterogeneity as well as boundary constrains. This study integrates physics-based modeling and image-based data acquisition to develop the patient-specific biomechanical model and consequently establish the first consistent Young\u27s modulus (YM) of human lung. This dissertation has four major components: (i) develop biomechanical model for computation of the flow and deformation characteristics that can utilize subject-specific, spatially-dependent lung material property; (ii) develop a fusion algorithm to integrate deformation results from a deformable image registration (DIR) and physics-based modeling using the theory of Tikhonov regularization; (iii) utilize fusion algorithm to establish unique and consistent patient specific Young\u27s modulus and; (iv) validate biomechanical model utilizing established patient-specific elastic property with imaging data. The simulation is performed on three dimensional lung geometry reconstructed from four-dimensional computed tomography (4DCT) dataset of human subjects. The heterogeneous Young\u27s modulus is estimated from a linear elastic deformation model with the same lung geometry and 4D lung DIR. The biomechanical model adequately predicts the spatio-temporal lung deformation, consistent with data obtained from imaging. The accuracy of the numerical solution is enhanced through fusion with the imaging data beyond the classical comparison of the two sets of data. Finally, the fused displacement results are used to establish unique and consistent patient-specific elastic property of the lung

Numerical modelling of the growth and remodelling phenomena in biological tissues

Living biological tissues are complex structures that have the capacity of evolving in response to external loads and environmental stimuli. The adequate modelling of soft biological tissue behaviour is a key issue in successfully reproducing biomechanical problems through computational analysis. This study presents a general constitutive formulation capable of representing the behaviour of these tissues through finite element simulation. It is based on phenomenological models that, used in combination with the generalized mixing theory, can numerically reproduce a wide range of material behaviours. First, the passive behaviour of tissues is characterized by means of hyperelastic and finite-strain damage models. A new generalized damage model is proposed, providing a flexible and versatile formulation that can reproduce a wide range of tissue behaviour. It can be particularized to any hyperelastic model and requires identifying only two material parameters. Then, the use of these constitutive models with generalized mixing theory in a finite-strain framework is described and tools to account for the anisotropic behaviour of tissues are put forth. The active behaviour of tissues is characterized through constitutive models capable of reproducing the growth and remodelling phenomena. These are built on the hyperelastic and damage formulations described above and, thus, represent the active extension of the passive tissue behaviour. A growth model considering biological availability is used and extended to include directional growth. In addition, a novel constitutive model for homeostatic-driven turnover remodelling is presented and discussed. This model captures the stiffness recovery that occurs in healing tissues, understood as a recovery or reversal of damage in the tissue, which is driven by both mechanical and biochemical stimuli. Finally, the issue of correctly identifying the material parameters for computational modelling is addressed. An inverse method using optimization techniques is developed to facilitate the identification of these parameters.Els teixits biològics vius són estructures complexes que tenen la capacitat d'evolucionar en resposta a càrregues externes i estímuls ambientals. El modelat adequat del comportament del teixit biològic tou és un tema clau per poder reproduir amb èxit problemes biomecànics mitjançant anàlisi computacional. Aquest estudi presenta una formulació constitutiva general capaç de representar el comportament d'aquests teixits mitjançant la simulació amb elements finits. Es basa en models fenomenològics que, usats en combinació amb la teoria de mescles generalitzada, permeten reproduir numèricament un ampli ventall de comportaments materials. Primer, el comportament passiu dels teixits es caracteritza amb models hiperelàstics i de dany en grans deformacions. Es proposa un model generalitzat de dany que proporciona una formulació versàtil i flexible per poder reproduir una extensa gamma de conductes de teixits. Pot ser particularitzat amb qualsevol model hiperelàstic i requereix identificar tan sols dos paràmetres materials. Llavors, es descriu l'ús d'aquests models constitutius en conjunt amb la teoria generalitzada de mescles, desenvolupada en el marc de grans deformacions, i es presenten eines que permeten incorporar les propietats anisòtropes dels teixits. El comportament actiu dels teixits es caracteritza mitjançant models constitutius capaços de reproduir els fenòmens de creixement i remodelació. Aquests es construeixen sobre les formulacions d'hiperelasticitat i dany descrites anteriorment i, per tant, suposen l'extensió activa del comportament passiu del teixit. Es fa servir un model de creixement que té en compte la disponibilitat biològica de l'organisme, que després s'amplia per incloure dany direccional en el model. També es presenta i analitza un nou model constitutiu per al remodelat per renovació tendint a l’homeòstasi (homeostatic-driven turnover remodelling). Aquest model captura la recuperació de rigidesa que s'observa en teixits que es guareixen. Aquí, el remodelat s'entén com la recuperació o inversió del dany en el teixit i és motivat tant per estímuls mecànics com bioquímics. Finalment, s'aborda el tema de la identificació correcta dels paràmetres materials per al modelat computacional. Es desenvolupa un mètode invers que fa ús de tècniques d'optimització per facilitar la identificació d'aquests paràmetre

Book of Abstracts 15th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering and 3rd Conference on Imaging and Visualization

In this edition, the two events will run together as a single conference, highlighting the strong connection with the Taylor & Francis journals: Computer Methods in Biomechanics and Biomedical Engineering (John Middleton and Christopher Jacobs, Eds.) and Computer Methods in Biomechanics and Biomedical Engineering: Imaging and Visualization (JoãoManuel R.S. Tavares, Ed.). The conference has become a major international meeting on computational biomechanics, imaging andvisualization. In this edition, the main program includes 212 presentations. In addition, sixteen renowned researchers will give plenary keynotes, addressing current challenges in computational biomechanics and biomedical imaging. In Lisbon, for the first time, a session dedicated to award the winner of the Best Paper in CMBBE Journal will take place. We believe that CMBBE2018 will have a strong impact on the development of computational biomechanics and biomedical imaging and visualization, identifying emerging areas of research and promoting the collaboration and networking between participants. This impact is evidenced through the well-known research groups, commercial companies and scientific organizations, who continue to support and sponsor the CMBBE meeting series. In fact, the conference is enriched with five workshops on specific scientific topics and commercial software.info:eu-repo/semantics/draf

Biomechanical Modeling and Inverse Problem Based Elasticity Imaging for Prostate Cancer Diagnosis

Early detection of prostate cancer plays an important role in successful prostate cancer treatment. This requires screening the prostate periodically after the age of 50. If screening tests lead to prostate cancer suspicion, prostate needle biopsy is administered which is still considered as the clinical gold standard for prostate cancer diagnosis. Given that needle biopsy is invasive and is associated with issues including discomfort and infection, it is desirable to develop a prostate cancer diagnosis system that has high sensitivity and specificity for early detection with a potential to improve needle biopsy outcome. Given the complexity and variability of prostate cancer pathologies, many research groups have been pursuing multi-parametric imaging approach as no single modality imaging technique has proven to be adequate. While imaging additional tissue properties increases the chance of reliable prostate cancer detection and diagnosis, selecting an additional property needs to be done carefully by considering clinical acceptability and cost. Clinical acceptability entails ease with respect to both operating by the radiologist and patient comfort. In this work, effective tissue biomechanics based diagnostic techniques are proposed for prostate cancer assessment with the aim of early detection and minimizing the numbers of prostate biopsies. The techniques take advantage of the low cost, widely available and well established TRUS imaging method. The proposed techniques include novel elastography methods which were formulated based on an inverse finite element frame work. Conventional finite element analysis is known to have high computational complexity, hence computation time demanding. This renders the proposed elastography methods not suitable for real-time applications. To address this issue, an accelerated finite element method was proposed which proved to be suitable for prostate elasticity reconstruction. In this method, accurate finite element analysis of a large number of prostates undergoing TRUS probe loadings was performed. Geometry input and displacement and stress fields output obtained from the analysis were used to train a neural network mapping function to be used for elastopgraphy imaging of prostate cancer patients. The last part of the research presented in this thesis tackles an issue with the current 3D TRUS prostate needle biopsy. Current 3D TRUS prostate needle biopsy systems require registering preoperative 3D TRUS to intra-operative 2D TRUS images. Such image registration is time-consuming while its real-time implementation is yet to be developed. To bypass this registration step, concept of a robotic system was proposed which can reliably determine the preoperative TRUS probe position relative to the prostate to place at the same position relative to the prostate intra-operatively. For this purpose, a contact pressure feedback system is proposed to ensure similar prostate deformation during 3D and 2D image acquisition in order to bypass the registration step

Bridging spatiotemporal scales in biomechanical models for living tissues : from the contracting Esophagus to cardiac growth

Appropriate functioning of our body is determined by the mechanical behavior of our organs. An improved understanding of the biomechanical functioning of the soft tissues making up these organs is therefore crucial for the choice for, and development of, efficient clinical treatment strategies focused on patient-specific pathophysiology. This doctoral dissertation describes the passive and active biomechanical behavior of gastrointestinal and cardiovascular tissue, both in the short and long term, through computer models that bridge the cell, tissue and organ scale. Using histological characterization, mechanical testing and medical imaging techniques, virtual esophagus and heart models are developed that simulate the patient-specific biomechanical organ behavior as accurately as possible. In addition to the diagnostic value of these models, the developed modeling technology also allows us to predict the acute and chronic effect of various treatment techniques, through e.g. drugs, surgery and/or medical equipment. Consequently, this dissertation offers insights that will have an unmistakable impact on the personalized medicine of the future.Het correct functioneren van ons lichaam wordt bepaald door het mechanisch gedrag van onze organen. Een verbeterd inzicht in het biomechanisch functioneren van deze zachte weefsels is daarom van cruciale waarde voor de keuze voor, en ontwikkeling van, efficiënte klinische behandelingsstrategieën gefocust op de patiënt-specifieke pathofysiologie. Deze doctoraatsthesis brengt het passieve en actieve biomechanisch gedrag van gastro-intestinaal en cardiovasculair weefsel, zowel op korte als lange termijn, in kaart via computermodellen die een brug vormen tussen cel-, weefsel- en orgaanniveau. Aan de hand van histologische karakterisering, mechanische testen en medische beeldvormingstechnieken worden virtuele slokdarm- en hartmodellen ontwikkeld die het patiënt-specifieke orgaangedrag zo accuraat mogelijk simuleren. Naast de diagnostische waarde van deze modellen, laat de ontwikkelde modelleringstechnologie ook toe om het effect van verschillende behandelingstechnieken, via medicatie, chirurgie en/of medische apparatuur bijvoorbeeld, acuut en chronisch te voorspellen. Bijgevolg biedt deze doctoraatsthesis inzichten die een onmiskenbare impact zullen hebben op de gepersonaliseerde geneeskunde van de toekomst

Insights into infusion-based targeted drug delivery in brain: perspectives, challenges and opportunities

Targeted drug delivery in the brain is instrumental in the treatment of lethal brain diseases, such as glioblastoma multiforme, the most aggressive primary central nervous system tumour in adults. Infusion-based drug delivery techniques, which directly administer to the tissue for local treatment, as in convection-enhanced delivery (CED), provide an important opportunity; however, poor understanding of the pressure-driven drug transport mechanisms in the brain has hindered its ultimate success in clinical applications. In this review, we focus on the biomechanical and biochemical aspects of infusion-based targeted drug delivery in the brain and look into the underlying molecular level mechanisms. We discuss recent advances and challenges in the complementary field of medical robotics and its use in targeted drug delivery in the brain. A critical overview of current research in these areas and their clinical implications is provided. This review delivers new ideas and perspectives for further studies of targeted drug delivery in the brain

Study on the biomechanical properties of 3D printed blended esophageal stents with different structural parameters based on patient CT

Introduction: Esophageal stenting is a widely used treatment for esophageal diseases, which can also be used for adjuvant therapy and feeding after chemotherapy for esophageal cancer. The structural parameters of the stent have a significant impact on its mechanical properties and patient comfort.Methods: In the present work, we reconstructed the esophagus model based on the patient’s computed tomography (CT) data, and designed stents with different structural parameters. We used 3D printing technology to achieve rapid production of the designed stents by using Thermoplastic polyurethane (TPU)/Poly-ε-caprolactone (PCL) blends as the materials. The mechanical properties and effects on the esophagus of polymer stents with four different structural parameters of diameter, wall thickness, length and flaring were investigated by in vitro tests of radial compression and migration of the stents, as well as by finite element simulations of the stent implantation process in the esophagus and of the stent migration process. An artificial neural network model was established to predict the radial force of the stent and the maximum equivalent stress of the esophagus during implantation based on these four structural parameters.Results: The results show that wall thickness was the structural parameter that had the greatest impact on the radial force of the stent (statistically significant, p < 0.01), and flaring was the structural parameter that had the greatest impact on the maximum equivalent stress of the esophageal wall after stent implantation (statistically significant, p < 0.01). No. 6 stent had a maximum radial force of 18.07 N, which exceeded that of commercial esophageal stents and had good mechanical properties. And the maximum equivalent force on the esophagus caused by its implantation was only 30.39 kPa, which can improve patient comfort. The predicted values of the constructed back propagation (BP) neural network model had an error of less than 10% from the true values, and the overall prediction accuracies were both above 97%, which can provide guidance for optimizing the design of the stent and for clinical research.Discussion: 3D printing technology presents a wide range of applications for the rapid fabrication of personalized TPU/PCL blend stents that are more suitable for individual patients