Realistic tool-tissue interaction models for surgical simulation and planning

Surgical simulators present a safe and potentially effective method for surgical training, and can also be used in pre- and intra-operative surgical planning. Realistic modeling of medical interventions involving tool-tissue interactions has been considered to be a key requirement in the development of high-fidelity simulators and planners. The soft-tissue constitutive laws, organ geometry and boundary conditions imposed by the connective tissues surrounding the organ, and the shape of the surgical tool interacting with the organ are some of the factors that govern the accuracy of medical intervention planning.\ud \ud This thesis is divided into three parts. First, we compare the accuracy of linear and nonlinear constitutive laws for tissue. An important consequence of nonlinear models is the Poynting effect, in which shearing of tissue results in normal force; this effect is not seen in a linear elastic model. The magnitude of the normal force for myocardial tissue is shown to be larger than the human contact force discrimination threshold. Further, in order to investigate and quantify the role of the Poynting effect on material discrimination, we perform a multidimensional scaling study. Second, we consider the effects of organ geometry and boundary constraints in needle path planning. Using medical images and tissue mechanical properties, we develop a model of the prostate and surrounding organs. We show that, for needle procedures such as biopsy or brachytherapy, organ geometry and boundary constraints have more impact on target motion than tissue material parameters. Finally, we investigate the effects surgical tool shape on the accuracy of medical intervention planning. We consider the specific case of robotic needle steering, in which asymmetry of a bevel-tip needle results in the needle naturally bending when it is inserted into soft tissue. We present an analytical and finite element (FE) model for the loads developed at the bevel tip during needle-tissue interaction. The analytical model explains trends observed in the experiments. We incorporated physical parameters (rupture toughness and nonlinear material elasticity) into the FE model that included both contact and cohesive zone models to simulate tissue cleavage. The model shows that the tip forces are sensitive to the rupture toughness. In order to model the mechanics of deflection of the needle, we use an energy-based formulation that incorporates tissue-specific parameters such as rupture toughness, nonlinear material elasticity, and interaction stiffness, and needle geometric and material properties. Simulation results follow similar trends (deflection and radius of curvature) to those observed in macroscopic experimental studies of a robot-driven needle interacting with gels

Computational model of the human urinary bladder

The proposal of an artificial bladder is still a challenge to overcome. Bladder cancer is among the most frequent cases of oncologic diseases in United States and Europe. It is considered a major medical problem once this disease has high rates of reoccurrence, often leading to the extirpation of this organ. The most refined solution to replace this organ is the ileal bladder, which consists of a neobladder made of the patient’s intestinal tissue. Unfortunately this solution presents not only functional mechanical problems, described on the literature as voiding and leaking problems, but also biological ones (i.e. bone loss, given the absorption by the intestine of substances that should be eliminated from the organism). Urged by the urological community of the Hospital Clinic de Barcelona and backgrounded by its experience in the numerical simulation of biomedical structures, the Center of Numerical Methods in Engineering (CIMNE) had the initiative to provide the research of the mechanics of the urinary bladder and the simulation of fluid structure interaction (FSI) to account for the filling and voiding of this organ with urine. The Finite Element Method (FEM) simulation of the real bladder and the comprehensive understanding of the mechanics of this organ and its interaction with urine will give the possibility to propose geometrical improvements and study suitable materials for an artificial solution to address the cases on which the bladder needs to be removed. To reach this goal, first we proceeded to the bibliographic review of mathematical models of the urinary apparatus and to a comprehensive study of the physiology and dynamics of the bladder. A review of the major urological structures, kidney, ureter and urethra, takes place. To consider boundary conditions other surrounding structures to the urinary system are also studied. In the second part of the thesis, we propose the numerical model to study the human urinary bladder. The behavior of the detrusor muscle during filling and voiding of the bladder with urine and its ability to promote the storage of urine under low pressure need to be accurately represented, requiring the implementation of a non-linear constitutive model. The mathematical model needs to be capable to simulate the mechanical variables that govern this organ and the properties of the urine. The nonlinear behavior of living tissues is implemented and validated with examples from the literature. The quasi-incompressibility property of urine and the navierstokes equations for the fluid are taken into account. The geometry of the bladder needs to be taken into account, and the implementation of a 3D computational model obtained from the computerized tomography of a cadaver male adult is considered. The data has been treated to consider boundary conditions. Two models have been conceived: one meshed with four nodes tetrahedral and another meshed with shell elements. FSI must work for the simulation of filling and voiding of the bladder. Due to the close densities of the materials the scheme used to solve fluid-structure needs to be carefully selected. The proposed numerical model and the filling and voiding analysis are finally validated with standardized urodynamic tests. The final part of the thesis, the simulation of a neobladder is presented, being the first step to simulate numerically artificial materials for bladder replacement

Computational model of the human urinary bladder

La propuesta de una vejiga artificial es un obstáculo a trasponer. El cáncer de vejiga está entre los casos más frecuentes de enfermedades oncológicas en Estados Unidos y Europa. Ese cáncer es considerado un problema médico importante una vez que esa enfermedad presenta altas tasas de re-ocurrencia, muchas veces llevando a la remoción del órgano. La solución más sofisticada para remplazar ese órgano es la vejiga ileal, que consiste en una neovejiga hecha de tejido intestinal del enfermo. Desafortunadamente, esa solución presenta no solo problemas mecánicos funcionales, descritos en la literatura como problemas de vaciado y fuga, peo también problemas de orden biológica (como ejemplo pérdida ósea, debido a la absorción por el intestino de substancias que necesitan ser eliminadas del organismo). A través de la solicitación de la comunidad urológica del Hospital Clínico de Barcelona y con su experiencia en modelos numéricos para estructuras biomédicas, el Centro de Métodos Numéricos en Ingeniería (CIMNE) ha tenido la iniciativa de proporcionar actividad investigadora de la mecánica de la vejiga urinaria y de la simulación de interacción fluidoestructura para reproducir el llenado y vaciado de ese órgano con la orina. La simulación de la vejiga humana por el Método de los Elementos Finitos (FEM) y un completo entendimiento de la mecánica de ese órgano y de su interacción con la orina dará la posibilidad de proponer mejora en la geometría y de analizar materiales para la solución artificial en caso de remplazamiento de la vejiga. Para lograr ese objetivo, primeramente procedemos a una revisión bibliográfica de los modelos matemáticos del aparato urinario y un estudio comprehensivo de la fisiología y dinámica de la vejiga. Presentamos una revisión de las principales estructuras urológicas, riñón, uréter y uretra. Las estructuras anexas también son consideradas para entender las condiciones de contorno del problema estudiado. Posteriormente, proponemos el modelo constitutivo para estudiar la vejiga urinaria humana. El comportamiento del musculo detrusor durante llenado y vaciado de la vejiga con orina, su habilidad de retención de orina a baja presión debe ser correctamente representada por medio de la implementación de un modelo constitutivo no-lineal. El modelo matemático necesita representar las variables mecánicas que gobiernan ese órgano, y también las propiedades de la orina. El comportamiento no-lineal de tejidos vivos es implementado y validado con ejemplos de la literatura. La propiedad quasi-incompressible de la orina y las ecuaciones Navier-Stokes son consideradas para análisis del fluido. Para representar la geometría de la vejiga, implementamos un modelo computacional 3D a partir de imágenes de tomografía computadorizada de un cadáver adulto. Los datos son tratados para considerar las condiciones de contorno. Hemos construido dos modelos de malla: un mallado con tetrahedos de cuatro nodos y otro mallado con elementos de membrana de tres nodos. El esquema utilizado para calcular la interacción fluido-estructura debe ser adecuado para materiales de densidad muy parecidas. El análisis numérico de llenado y vaciado de la vejiga humana es validada con tests urodinámicos estandarizados. La parte final de la tesis, presentamos una simulación de una neo-vejiga, siendo el primer paso para representar numéricamente materiales artificiales para remplazamiento de la vejiga.The proposal of an artificial bladder is still a challenge to overcome. Bladder cancer is among the most frequent cases of oncologic diseases in United States and Europe. It is considered a major medical problem once this disease has high rates of reoccurrence, often leading to the extirpation of this organ. The most refined solution to replace this organ is the ileal bladder, which consists of a neobladder made of the patient’s intestinal tissue. Unfortunately this solution presents not only functional mechanical problems, described on the literature as voiding and leaking problems, but also biological ones (i.e. bone loss, given the absorption by the intestine of substances that should be eliminated from the organism). Urged by the urological community of the Hospital Clinic de Barcelona and backgrounded by its experience in the numerical simulation of biomedical structures, the Center of Numerical Methods in Engineering (CIMNE) had the initiative to provide the research of the mechanics of the urinary bladder and the simulation of fluid structure interaction (FSI) to account for the filling and voiding of this organ with urine. The Finite Element Method (FEM) simulation of the real bladder and the comprehensive understanding of the mechanics of this organ and its interaction with urine will give the possibility to propose geometrical improvements and study suitable materials for an artificial solution to address the cases on which the bladder needs to be removed. To reach this goal, first we proceeded to the bibliographic review of mathematical models of the urinary apparatus and to a comprehensive study of the physiology and dynamics of the bladder. A review of the major urological structures, kidney, ureter and urethra, takes place. To consider boundary conditions other surrounding structures to the urinary system are also studied. In the second part of the thesis, we propose the numerical model to study the human urinary bladder. The behavior of the detrusor muscle during filling and voiding of the bladder with urine and its ability to promote the storage of urine under low pressure need to be accurately represented, requiring the implementation of a non-linear constitutive model. The mathematical model needs to be capable to simulate the mechanical variables that govern this organ and the properties of the urine. The nonlinear behavior of living tissues is implemented and validated with examples from the literature. The quasi-incompressibility property of urine and the navierstokes equations for the fluid are taken into account. The geometry of the bladder needs to be taken into account, and the implementation of a 3D computational model obtained from the computerized tomography of a cadaver male adult is considered. The data has been treated to consider boundary conditions. Two models have been conceived: one meshed with four nodes tetrahedral and another meshed with shell elements. FSI must work for the simulation of filling and voiding of the bladder. Due to the close densities of the materials the scheme used to solve fluid-structure needs to be carefully selected. The proposed numerical model and the filling and voiding analysis are finally validated with standardized urodynamic tests. The final part of the thesis, the simulation of a neobladder is presented, being the first step to simulate numerically artificial materials for bladder replacement

Towards Individualized Transcranial Electric Stimulation Therapy through Computer Simulation

Transkranielle Elektrostimulation (tES) beschreibt eine Gruppe von Hirnstimulationstechniken, die einen schwachen elektrischen Strom über zwei nicht-invasiv am Kopf angebrachten Elektroden applizieren. Handelt es sich dabei um einen Gleichstrom, spricht man von transkranieller Gleichstromstimulation, auch tDCS abgekürzt. Die allgemeine Zielstellung aller Hirnstimulationstechniken ist Hirnfunktion durch ein Verstärken oder Dämpfen von Hirnaktivität zu beeinflussen. Unter den Stimulationstechniken wird die transkranielle Gleichstromstimulation als ein adjuvantes Werkzeug zur Unterstützung der mikroskopischen Reorganisation des Gehirnes in Folge von Lernprozessen und besonders der Rehabilitationstherapie nach einem Schlaganfall untersucht. Aktuelle Herausforderungen dieser Forschung sind eine hohe Variabilität im erreichten Stimulationseffekt zwischen den Probanden sowie ein unvollständiges Verständnis des Zusammenspiels der der Stimulation zugrundeliegenden Mechanismen. Als Schlüsselkomponente für das Verständnis der Stimulationsmechanismen wird das zwischen den Elektroden im Kopf des Probanden aufgebaute elektrische Feld erachtet. Einem grundlegenden Konzept folgend wird angenommen, dass Hirnareale, die einer größeren elektrischen Feldstärke ausgesetzt sind, ebenso einen höheren Stimulationseffekt erfahren. Damit kommt der Positionierung der Elektroden eine entscheidende Rolle für die Stimulation zu. Allerdings verteilt sich das elektrische Feld wegen des heterogenen elektrischen Leitfähigkeitsprofil des menschlichen Kopfes nicht uniform im Gehirn der Probanden. Außerdem ist das Verteilungsmuster auf Grund anatomischer Unterschiede zwischen den Probanden verschieden. Die triviale Abschätzung der Ausbreitung des elektrischen Feldes anhand der bloßen Position der Stimulationselektroden ist daher nicht ausreichend genau für eine zielgerichtete Stimulation. Computerbasierte, biophysikalische Simulationen der transkraniellen Elektrostimulation ermöglichen die individuelle Approximation des Verteilungsmusters des elektrischen Feldes in Probanden basierend auf deren medizinischen Bildgebungsdaten. Sie werden daher zunehmend verwendet, um tDCS-Anwendungen zu planen und verifizieren, und stellen ein wesentliches Hilfswerkzeug auf dem Weg zu individualisierter Schlaganfall-Rehabilitationstherapie dar. Softwaresysteme, die den dahinterstehenden individualisierten Verarbeitungsprozess erleichtern und für ein breites Feld an Forschern zugänglich machen, wurden in den vergangenen Jahren für den Anwendungsfall in gesunden Erwachsenen entwickelt. Jedoch bleibt die Simulation von Patienten mit krankhaftem Hirngewebe und strukturzerstörenden Läsionen eine nicht-triviale Aufgabe. Daher befasst sich das hier vorgestellte Projekt mit dem Aufbau und der praktischen Anwendung eines Arbeitsablaufes zur Simulation transkranieller Elektrostimulation. Dabei stand die Anforderung im Vordergrund medizinische Bildgebungsdaten insbesondere neurologischer Patienten mit krankhaft verändertem Hirngewebe verarbeiten zu können. Der grundlegende Arbeitsablauf zur Simulation wurde zunächst für gesunde Erwachsene entworfen und validiert. Dies umfasste die Zusammenstellung medizinischer Bildverarbeitungsalgorithmen zu einer umfangreichen Verarbeitungskette, um elektrisch relevante Strukturen in den Magnetresonanztomographiebildern des Kopfes und des Oberkörpers der Probanden zu identifizieren und zu extrahieren. Die identifizierten Strukturen mussten in Computermodelle überführt werden und das zugrundeliegende, physikalische Problem der elektrischen Volumenleitung in biologischen Geweben mit Hilfe numerischer Simulation gelöst werden. Im Verlauf des normalen Alterns ist das Gehirn strukturellen Veränderungen unterworfen, unter denen ein Verlust des Hirnvolumens sowie die Ausbildung mikroskopischer Veränderungen seiner Nervenfaserstruktur die Bedeutendsten sind. In einem zweiten Schritt wurde der Arbeitsablauf daher erweitert, um diese Phänomene des normalen Alterns zu berücksichtigen. Die vordergründige Herausforderung in diesem Teilprojekt war die biophysikalische Modellierung der veränderten Hirnmikrostruktur, da die resultierenden Veränderungen im Leitfähigkeitsprofil des Gehirns bisher noch nicht in der Literatur quantifiziert wurden. Die Erweiterung des Simulationsablauf zeichnete sich vorrangig dadurch aus, dass mit unsicheren elektrischen Leitfähigkeitswerten gearbeitet werden konnte. Damit war es möglich den Einfluss der ungenau bestimmbaren elektrischen Leitfähigkeit der verschiedenen biologischen Strukturen des menschlichen Kopfes auf das elektrische Feld zu ermitteln. In einer Simulationsstudie, in der Bilddaten von 88 Probanden einflossen, wurde die Auswirkung der veränderten Hirnfaserstruktur auf das elektrische Feld dann systematisch untersucht. Es wurde festgestellt, dass sich diese Gewebsveränderungen hochgradig lokal und im Allgemeinen gering auswirken. Schließlich wurden in einem dritten Schritt Simulationen für Schlaganfallpatienten durchgeführt. Ihre großen, strukturzerstörenden Läsionen wurden dabei mit einem höheren Detailgrad als in bisherigen Arbeiten modelliert und physikalisch abermals mit unsicheren Leitfähigkeiten gearbeitet, was zu unsicheren elektrischen Feldabschätzungen führte. Es wurden individuell berechnete elektrische Felddaten mit der Hirnaktivierung von 18 Patienten in Verbindung gesetzt, unter Berücksichtigung der inhärenten Unsicherheit in der Bestimmung der elektrischen Felder. Das Ziel war zu ergründen, ob die Hirnstimulation einen positiven Einfluss auf die Hirnaktivität der Patienten im Kontext von Rehabilitationstherapie ausüben und so die Neuorganisierung des Gehirns nach einem Schlaganfall unterstützen kann. Während ein schwacher Zusammenhang hergestellt werden konnte, sind weitere Untersuchungen nötig, um diese Frage abschließend zu klären.:Kurzfassung Abstract Contents 1 Overview 2 Anatomical structures in magnetic resonance images 2 Anatomical structures in magnetic resonance images 2.1 Neuroanatomy 2.2 Magnetic resonance imaging 2.3 Segmentation of MR images 2.4 Image morphology 2.5 Summary 3 Magnetic resonance image processing pipeline 3.1 Introduction to human body modeling 3.2 Description of the processing pipeline 3.3 Intermediate and final outcomes in two subjects 3.4 Discussion, limitations & future work 3.5 Conclusion 4 Numerical simulation of transcranial electric stimulation 4.1 Electrostatic foundations 4.2 Discretization of electrostatic quantities 4.3 The numeric solution process 4.4 Spatial discretization by volume meshing 4.5 Summary 5 Simulation workflow 5.1 Overview of tES simulation pipelines 5.2 My implementation of a tES simulation workflow 5.3 Verification & application examples 5.4 Discussion & Conclusion 6 Transcranial direct current stimulation in the aging brain 6.1 Handling age-related brain changes in tES simulations 6.2 Procedure of the simulation study 6.3 Results of the uncertainty analysis 6.4 Findings, limitations and discussion 7 Transcranial direct current stimulation in stroke patients 7.1 Bridging the gap between simulated electric fields and brain activation in stroke patients 7.2 Methodology for relating simulated electric fields to functional MRI data 7.3 Evaluation of the simulation study and correlation analysis 7.4 Discussion & Conclusion 8 Outlooks for simulations of transcranial electric stimulation List of Figures List of Tables Glossary of Neuroscience Terms Glossary of Technical Terms BibliographyTranscranial electric current stimulation (tES) denotes a group of brain stimulation techniques that apply a weak electric current over two or more non-invasively, head-mounted electrodes. When employing a direct-current, this method is denoted transcranial direct current stimulation (tDCS). The general aim of all tES techniques is the modulation of brain function by an up- or downregulation of brain activity. Among these, transcranial direct current stimulation is investigated as an adjuvant tool to promote processes of the microscopic reorganization of the brain as a consequence of learning and, more specifically, rehabilitation therapy after a stroke. Current challenges of this research are a high variability in the achieved stimulation effects across subjects and an incomplete understanding of the interplay between its underlying mechanisms. A key component to understanding the stimulation mechanism is considered the electric field, which is exerted by the electrodes and distributes in the subjects' heads. A principle concept assumes that brain areas exposed to a higher electric field strength likewise experience a higher stimulation. This attributes the positioning of the electrodes a decisive role for the stimulation. However, the electric field distributes non-uniformly across subjects' brains due to the heterogeneous electrical conductivity profile of the human head. Moreover, the distribution pattern is variable between subjects due to their individual anatomy. A trivial estimation of the distribution of the electric field solely based on the position of the stimulating electrodes is, therefore, not precise enough for a well-targeted stimulation. Computer-based biophysical simulations of transcranial electric stimulation enable the individual approximation of the distribution pattern of the electric field in subjects based on their medical imaging data. They are, thus, increasingly employed for the planning and verification of tDCS applications and constitute an essential tool on the way to individualized stroke rehabilitation therapy. Software pipelines facilitating the underlying individualized processing for a wide range of researchers have been developed for use in healthy adults over the past years, but, to date, the simulation of patients with abnormal brain tissue and structure disrupting lesions remains a non-trivial task. Therefore, the presented project was dedicated to establishing and practically applying a tES simulation workflow. The processing of medical imaging data of neurological patients with abnormal brain tissue was a central requirement in this process. The basic simulation workflow was first designed and validated for the simulation of healthy adults. This comprised compiling medical image processing algorithms into a comprehensive workflow to identify and extract electrically relevant physiological structures of the human head and upper torso from magnetic resonance images. The identified structures had to be converted to computational models. The underlying physical problem of electric volume conduction in biological tissue was solved by means of numeric simulation. Over the course of normal aging, the brain is subjected to structural alterations, among which a loss of brain volume and the development of microscopic alterations of its fiber structure are the most relevant. In a second step, the workflow was, thus, extended to incorporate these phenomena of normal aging. The main challenge in this subproject was the biophysical modeling of the altered brain microstructure as the resulting alterations to the conductivity profile of the brain were so far not quantified in the literature. Therefore, the augmentation of the workflow most notably included the modeling of uncertain electrical properties. With this, the influence of the uncertain electrical conductivity of the biological structures of the human head on the electric field could be assessed. In a simulation study, including imaging data of 88 subjects, the influence of the altered brain fiber structure on the electric field was then systematically investigated. These tissue alterations were found to exhibit a highly localized and generally low impact. Finally, in a third step, tDCS simulations of stroke patients were conducted. Their large, structure-disrupting lesions were modeled in a more detailed manner than in previous stroke simulation studies, and they were physically, again, modeled by uncertain electrical conductivity resulting in uncertain electric field estimates. Individually simulated electric fields were related to the brain activation of 18 patients, considering the inherently uncertain electric field estimations. The goal was to clarify whether the stimulation exerts a positive influence on brain function in the context of rehabilitation therapy supporting brain reorganization following a stroke. While a weak correlation could be established, further investigation will be necessary to answer that research question.:Kurzfassung Abstract Contents 1 Overview 2 Anatomical structures in magnetic resonance images 2 Anatomical structures in magnetic resonance images 2.1 Neuroanatomy 2.2 Magnetic resonance imaging 2.3 Segmentation of MR images 2.4 Image morphology 2.5 Summary 3 Magnetic resonance image processing pipeline 3.1 Introduction to human body modeling 3.2 Description of the processing pipeline 3.3 Intermediate and final outcomes in two subjects 3.4 Discussion, limitations & future work 3.5 Conclusion 4 Numerical simulation of transcranial electric stimulation 4.1 Electrostatic foundations 4.2 Discretization of electrostatic quantities 4.3 The numeric solution process 4.4 Spatial discretization by volume meshing 4.5 Summary 5 Simulation workflow 5.1 Overview of tES simulation pipelines 5.2 My implementation of a tES simulation workflow 5.3 Verification & application examples 5.4 Discussion & Conclusion 6 Transcranial direct current stimulation in the aging brain 6.1 Handling age-related brain changes in tES simulations 6.2 Procedure of the simulation study 6.3 Results of the uncertainty analysis 6.4 Findings, limitations and discussion 7 Transcranial direct current stimulation in stroke patients 7.1 Bridging the gap between simulated electric fields and brain activation in stroke patients 7.2 Methodology for relating simulated electric fields to functional MRI data 7.3 Evaluation of the simulation study and correlation analysis 7.4 Discussion & Conclusion 8 Outlooks for simulations of transcranial electric stimulation List of Figures List of Tables Glossary of Neuroscience Terms Glossary of Technical Terms Bibliograph

Integration of biomechanical models into image registration in the presence of large deformations

Prone-to-supine breast image registration has potential application in the fields of surgical and radiotherapy planning, and image guided interventions. However, breast image registration of three-dimensional images acquired in different patient positions is a challenging problem, due to large deformations induced to the soft breast tissue caused by the change in gravity loading. Biomechanical modelling is a promising tool to predict gravity induced deformations, however such simulations alone are unlikely to produce good alignment due to inter-patient variability and image acquisition related influences on the breast shape. This thesis presents a symmetric, biomechanical simulation based registration framework which aligns images in a central, stress-free configuration. Soft tissue is modelled as a neo-Hookean material and external forces are considered as the main source of deformation in the original images. The framework successively applies image derived forces directly into the unloading simulation in place of a subsequent image registration step. This results in a biomechanically constrained deformation. Using a finite difference scheme enables simulations to be performed directly in the image space. Motion constrained boundary conditions have been incorporated which can capture tangential motion of membranes and fasciae. The accuracy of the approach is assessed by measuring the target registration error (TRE) using nine prone MRI and supine CT image pairs, one prone-supine CT image pair, and four prone-supine MRI image pairs. The registration reduced the combined mean TRE for all clinical data sets from initially 69.7mm to 5.6mm. Prone-supine image pairs might not always be available in the clinical breast cancer workflow, especially prior to surgery. Hence an alternative surface driven registration methodology was also developed that incorporates biomechanical simulations, material parameter optimisation, and constrained surface matching. For three prone MR images and corresponding supine CT-derived surfaces a final mean TRE of 10.0mm was measured

Shape analysis of the human brain.

Autism is a complex developmental disability that has dramatically increased in prevalence, having a decisive impact on the health and behavior of children. Methods used to detect and recommend therapies have been much debated in the medical community because of the subjective nature of diagnosing autism. In order to provide an alternative method for understanding autism, the current work has developed a 3-dimensional state-of-the-art shape based analysis of the human brain to aid in creating more accurate diagnostic assessments and guided risk analyses for individuals with neurological conditions, such as autism. Methods: The aim of this work was to assess whether the shape of the human brain can be used as a reliable source of information for determining whether an individual will be diagnosed with autism. The study was conducted using multi-center databases of magnetic resonance images of the human brain. The subjects in the databases were analyzed using a series of algorithms consisting of bias correction, skull stripping, multi-label brain segmentation, 3-dimensional mesh construction, spherical harmonic decomposition, registration, and classification. The software algorithms were developed as an original contribution of this dissertation in collaboration with the BioImaging Laboratory at the University of Louisville Speed School of Engineering. The classification of each subject was used to construct diagnoses and therapeutic risk assessments for each patient. Results: A reliable metric for making neurological diagnoses and constructing therapeutic risk assessment for individuals has been identified. The metric was explored in populations of individuals having autism spectrum disorders, dyslexia, Alzheimers disease, and lung cancer. Conclusion: Currently, the clinical applicability and benefits of the proposed software approach are being discussed by the broader community of doctors, therapists, and parents for use in improving current methods by which autism spectrum disorders are diagnosed and understood

A COMPUTATIONAL APPROACH TO FRETTING WEAR PREDICTION IN TOTAL HIP REPLACEMENTS

A challenge in engineering coupling design is the understanding of performance of contact geometry for a given application. “Wear” is one of a number of mechanical failures that can occur in mechanical coupling design. “Fretting wear” occurs where surfaces in contact are subjected to oscillating load and very small relative motion over a period of time. Fretting has been observed in many mechanical interactions and is known to be a reason for failure in many designs.Recent evidence suggests that fretting wear occurs at the taper junction of modular total hip replacements and leads to failure of the implants. Experimental testing to determine the wear behaviour that occurs in mechanical devices is time consuming, expensive and complicated. Computational wear modelling is an alternative method which is faster and cheaper than real testing and can be used in addition to testing to help improve component design and enhance wear characteristics. Developing an algorithm that can accurately predict fretting wear considering linear wear, volumetric wear and surface wear damage is the main focus of this thesis.The thesis proposes a new computational methodology incorporating published wear laws into commercial finite element code to predict fretting wear which could occur at the taper junction of total hip replacements. The assessment of wear in this study is solely based on mechanical wear (fretting) as being the primary mechanism causing surface damage. The method is novel in that it simulates the weakening of the initial taper ‘fixation’ (created at impaction of the head onto the stem in surgery) due to the wearing process. The taper fixation is modelled using a contact analysis with overlapped meshes at the taper junction. The reduction in fixation is modelled by progressive removal of the overlap between components based on calculated wear depth and material loss.The method has been used for three different studies to determine surface wear damage, linear and volumetric wear rates that could occur at taper junction of total hip replacements over time. The results obtained are consistent with those found from observation and measurement of retrieved prostheses. The fretting wear analysis approach has been shown to model the evolution of wear effectively; however, it has been shown that accurate, quantitative values for wear are critically dependant on mesh refinement, wear fraction and scaling factor, wear coefficient used and knowledge of the device loading history. The numerical method presented could be used to consider the effect of design changes and clinical technique on subsequent fretting wear in modular prosthetic devices or other mechanically coupled designs

Experimental characterisation of breast tissues and its application to a numerical model of a healthy breast

In this work, a great contribution to the knowledge of the biomechanics of the breast has been done. None of the previous works were valid to simulate the real movement of the breast and a little knowledge existed about many factors which play an important role in the behaviour of the breast. We have gone in depth in this field and provided the path that must be followed in the future computational and experimental studies about the breast. Many possibilities have been discarded shedding light on the way the development of the finite element model of the breast should be carried out. Moreover, the difficult interaction between the adipose tissue and the pectoral muscle has been pointed out as key in the process. Concerning the experimental work, a lot of relaxation test have been done in human adipose tissue, in the abdomen and in the breast. Different patients and areas have been tested. Two different viscoelastic models (with several hyperelastic strain energy functions) were adjusted to the experimental tests, providing very good results. For both of them, the independency of their constants with respect to the strain rate was proved, although the independency with respect to the strain level was not accomplished. That means that it is not possible to define a unique set of constants for the adipose tissue with these two models. Probably the tissue is suffering some damage at the different strain levels, making the constants dependent on it. This damage should be studied more carefully and a damage model should be used in case the degradation was confirmed. In spite of this fact, for a certain strain level, both models are valid, being the internal variables viscoelastic model, with an Ogden strain energy function, the formulation that adjusted the experimental results more accurately. Several comparisons have been made to analyse the differences between the mechanical behaviour of the adipose tissue of different areas and individuals. The mechanical behaviour of different individuals' abdominal fat was compared. Inter-individual differences were found in both, the elastic and the viscous constants, confirming that it was a correct decision to extract the specimens from the same individual in the subsequent statistical analyses, for example, to check the validity of the QLV and IVV models or to compare the adipose tissue from different anatomical regions. It is therefore advisable to extract the specimens from the same patient if avoiding the inter-individual effects is desired. In the comparison of the mechanical properties of the adipose tissue of several regions of the abdomen and the breast, differences were found between the superficial breast and three groups of the abdomen: superficial-medial, deep-medial and deep-lateral. However, there are no differences with the superficial-lateral group. No differences were detected between the deep breast and the rest of the groups either. These conclusions have a high relevance for the breast reconstruction surgery with autologous abdominal tissue. The breast adipose tissue can be considered as a unique tissue from the mechanical point of view. Moreover, in the breast reconstruction surgery, the deep breast fat can be replaced by any part of the abdomen, since no significant differences exist in the mechanical properties. However, the superficial breast fat should be replaced, if possible, by the superficial lateral region of the abdomen. Also important although with less clinical relevance are the differences found between regions of the abdominal adipose tissue. It seems that no differences exist in the mechanical properties between both regions of the superficial layer, between both parts of the deep layer and between both parts of the medial regions. However, differences between the deep and superficial layers were found, that is to say, the mechanical properties of the abdominal adipose tissue seem to change with the depth. Comparing the elastic part of the final model presented here for the breast adipose tissue with the Samani's constants (which are the only ones found in the literature for the breast fat), it can be seen that the behaviour modelled with the Samani's constants is much stiffer than that measured experimentally in this thesis. Also supported by the results obtained in the FE models, it seems that the constants provided by Samani do not correspond to the real behaviour of the breast adipose tissue. Regarding the computational work, several models, boundary conditions and strain energy functions for different materials have been tried. The deformed shape of the deformed breast model from supine to prone position has been improved much from the initial models, although some issues need to be solved yet to improve the models and finally obtain a deformation which can be considered valid. It has been found that none of the material models and boundary conditions proposed in the literature produce reasonable results. In particular, they yield an excessively stiff behaviour. The interaction between the muscle and the breast tissue has been detected to play a key role in the deformation of the breast. The properties of the muscle are not determinant, as the muscle is not activated during the change of position modelled here and, moreover, it is stiffer than the rest of the involved tissues. Of course, if an activity in which the dynamics matter, like running, is under study, the role of the muscle can change. The skin properties can be important in the global behaviour because it is the tissue which surrounds the organ. In general, a deeper knowledge about the mechanical properties of the materials is needed. Normally, these properties have been determined in the literature with one “simple" experimental test, whereas the deformation in the breast is not simple whatsoever and quite different from the experimental test which was carried out. This can lead to wrong results when using these mechanical properties in a computational model. In addition, more studies are needed about the internal structure of the tissues and their connections

A 3D Reconstruction Method of Bone Shape from Un-calibrated Radiographs

학위논문 (박사)-- 서울대학교 대학원 : 공과대학 컴퓨터공학부, 2019. 2. 이제희.전산화 단층촬영(CT)은 골형상을 3차원으로 시각화하여 직관적으로 병증을 진단할 수 있다는 장점이 있다. 하지만 과도한 방사선 노출로 인해 암과 같은 부작용의 우려가 있기 때문에 EOS®와 같이 저선량으로 3차원 재건을 할 수 있는 양판 촬영 시스템이 대안으로 제시되었다. 그러나 이 시스템은 도입 비용이 높기 때문에 일부 병원이나 국가에서는 사용이 어렵다. 본 논문에서는 어느 환경의 병원에서든지 3차원 진단을 할 수 있도록 단순 방사선 영상만으로 3차원 재건을 하는 방법을 제안한다. 이 방법은 별도의 금속 보정물체 없이 단순 영상을 자가 보정하는 것에 참신성이 있다. 기술적으로는 통계형상의 모델과 영상내의 윤곽선이 일치하도록 보정과 형상재건을 번갈아 반복하는 방법을 사용한다. 또한, 위의 기술을 의료환경에 적용하기 위해 제안한 재건 방법을 포함하는 모바일 어플리케이션을 제시한다. 사용자는 모니터 화면이나 필름을 모바일 기기의 카메라로 촬영하여 입력할 수 있으며, 그래프 컷 방법을 통해 윤곽선을 자동으로 추출하고 터치 입력으로 손쉽게 윤곽선을 수정할 수 있다. 우리는 우선적으로 대퇴골 재건 모바일 어플리케이션을 개발하였고, 대퇴골 염전각 진단에 있어서 훌륭한 신뢰도와 CT와 높은 동시 타당도를 갖는 것으로 측정되었다.Computed tomography (CT) provides benefits in accurate diagnosis of bone deformity. However, the potential adverse effects of radiation exposure in CT has become a concern. To reduce radiation dose while maintaining the accuracy of diagnosis, the EOS® system has been proposed to reconstruct 3D bony shapes from calibrated bi-planar(stereo) X-ray images. However, this system requires another apparatus in addition to the conventional radiographic system, and the cost for the device installation is high and the space occupied is substantial. Purchasing an EOS® system only for 3D reconstruction may hence not be appropriate in some hospitals or countries. In this thesis, we propose a new method to reconstruct 3D bone shape only from conventional radiograph so that hospitals in any environment can perform 3D diagnosis. It has novelty in self-calibrating conventional radiograph without metal calibration object. Technically, the calibration and reconstruction were optimized by minimizing the difference between the projected contour of the bone shape and the contour of the radiographic image. To apply the above technology to a medical situation, we present a mobile application including the reconstruction method. The user can easily input a printed film or a digital image displayed on a monitor screen by taking a photograph using an embedded camera. The application provides automatic contouring with a graph-cut algorithm, but also an intuitive touch interface for modifying the contour of a radiograph. We first developed a femur reconstruction, and the measurement of femoral anteversion with the mobile application showed excellent concurrent validity and reliability.제 1장 서론 1 제 2장 배경지식 5 2.1 전산화단층 촬영 3차원 재건 기법 5 2.2 임상에서 3차원 형상의 용도 8 2.3 양판(bi-planar) 3차원 재건 시스템 11 2.4 단순 방사선 촬영 15 제 3장 통계형상모델(statistical shape model) 17 3.1 연관 논문 18 3.2 형상의 표현방법 19 3.3 두 3차원 표면의 대응점 찾기 22 3.3.1 미분 기하 25 3.3.2 열 확산 방정식과 형상의 특징 35 3.4 주성분 분석 기법(PCA) 38 3.5 뼈의 통계형상 모델 생성 방법 40 3.5.1 매끄러운 표면의 특징을 찾는 방법 41 3.5.2 대퇴골의 점 분포 모델에 외적대응 방식의 적용 42 3.5.3 거골과 대퇴골의 점 분포 모델에 내적 대응 방식의 적용 43 제4장 방사선 영상에서 골 윤곽선의 추출 48 4.1 연관 논문 49 4.2 그래프 절단을 이용한 영상 분할 49 4.2.1 사용자 입력과 최소 절단을 사용하는 방법 50 4.2.2 정규화 절단(Normalized cut) 51 4.3 골 경계선 추출 방법 53 4.3.1 그래프 최소절단 방식 영상 분할 54 4.3.2 지정한 점을 지나는 최소 가중치 경로 방식 54 4.3.3 방향성 그래프의 경로찾기 방식 58 제5장 단순 방사선 영상의 자가보정 65 5.1 Perspective N Points(PNP)문제의 반복적 해 65 5.2 통계형상모델을 보정물체로 사용하는 자가보정 방법 68 제6장 단순 방사선 3차원 재건 시스템 71 6.1 통계형상의 변형 72 6.2 볼륨 렌더링을 이용한 가상 엑스레이 생성 73 6.3 대퇴골 재건 시스템 75 6.3.1 자가보정 정확도 실험 76 6.3.2 재건 형상의 거리 오차 78 6.4 대퇴골 재건 모바일 앱 79 6.5 경비로 재건 모바일 앱 83 제7장 결론 86 Abstract 96Docto