3D Subject-Atlas Image Registration for Micro-Computed Tomography Based Characterization of Drug Delivery in the Murine Cochlea

A wide variety of hearing problems can potentially be treated with local drug delivery systems capable of delivering drugs directly to the cochlea over extended periods of time. Developing and testing such systems requires accurate quantification of drug concentration over time. A variety of techniques have been proposed for both direct and indirect measurement of drug pharmacokinetics; direct techniques are invasive, whereas many indirect techniques are imprecise because they rely on assumptions about the relationship between physiological response and drug concentrations. One indirect technique, however, is capable of quantifying drug pharmacokinetics very precisely: Micro-Computed tomography (micro-CT) can provide a non-invasive way to measure the concentration of a contrast agent in the cochlea over time. In this thesis, we propose a systematic approach for analyzing micro-CT images to measure concentrations of the contrast agent ioversol in mouse cochlea. This approach requires segmenting and classifying the intra-cochlea structures from micro-CT images, which is done via 3D atlas-subject registration to a published atlas of the mouse cochlea. Labels of each intra-cochlear structure in the atlas are propagated through the registration transformation to the corresponding structures in the micro-CT images. Pixel intensities are extracted from three key intra-cochlea structures: scala tympani (ST), scala vestibuli (SV), scala media (SM) in the micro-CT images, and these intensities are mapped into concentrations using a linear model between solution concentration and image intensity that is determined in a previous calibration step. To localize this analysis, the ST, SV, SM are divided into several discrete components, and the concentrations are estimated in each component using a weighted average with weights determined by solving a nonhomogeneous Poisson equation with Dirichlet boundary conditions on the component boundaries. We illustrate this entire system on a series of micro-CT images of an anesthetized mouse that include a baseline scan (with no contrast agent) and a series of scans after injection of ioversol into the cochlea

Automated analysis of human cochlea shape variability from segmented μCT images

International audienceThe aim of this study is to define an automated and reproducible framework for cochlear anatomical analysis from high-resolution segmented images and to provide a comprehensive and objective shape variability study suitable for cochlear implant design and surgery planning. For the scala tympani (ST), the scala vestibuli (SV) and the whole cochlea, the variability of the arc lengths and the radial and longitudinal components of the lateral, central and modiolar paths are studied. The robustness of the automated cochlear coordinate system estimation is validated with synthetic and real data. Cochlear cross-sections are statistically analyzed using area, height and width measurements. The cross-section tilt angle is objectively measured and this data documents a significant feature for occurrence of surgical trauma

Three-dimensional models of cochlear implants : a review of their development and how they could support management and maintenance of cochlear implant performance

Three-dimensional (3D) computational modelling of the auditory periphery forms an integral part of modern-day research in cochlear implants (CIs). These models consist of a volume conduction description of implanted stimulation electrodes and the current distribution around these, coupled to auditory nerve fibre models. Cochlear neural activation patterns can then be predicted for a given input stimulus. The objective of this article is to present the context of 3D modelling within the field of CIs, the different models and approaches to models that have been developed over the years, as well as the applications and potential applications of these models. The process of development of 3D models is discussed, and the article places specific emphasis on the complementary roles of generic models and user-specific models, as the latter is important for translation of these models into clinical application.http://tandfonline.com/toc/inet202017-05-31hb2016Electrical, Electronic and Computer Engineerin

Modelado 3D & Análisis Numérico del Oído Interno mediante Elementos Finitos

Para validar los resultados se han comparado con los datos de publicaciones existentes. Como conclusión principal de esta tesis se tiene que se ha conseguido crear satisfactoriamente un Modelo de Elementos Finitos del Oído Interno mediante un algoritmo semiautomático lo más realista posible. Otra conclusión obtenida, es que el análisis de la Impedancia no depende en gran medida de la geometría del oído interno, obteniéndose valores semejantes en los resultados a modelos más simples de la literatura, no obstante, respecto a la Energía Absorbida, los resultados obtenidos muestran algunas diferencias. Fecha de lectura de Tesis Doctoral: 21 noviembre 2019La presente tesis constituye una nueva aportación al estudio del oído interno del Sistema Auditivo Humano. El objetivo primordial es realizar un modelo del oído interno, en elementos finitos, lo más representativo posible de la realidad. Para ello se ha realizado un algoritmo semiautomático que utiliza la información geométrica obtenida de 19 tomografías sacadas del modelo EPL-3D, a través de procesamiento de imágenes, para crear el modelo geométrico que consta de una cóclea en espiral, compuesta por escala vestibular, escala timpánica, membrana basilar, membrana de Reissner y ventana redonda; acoplada a la cadena osicular con su modelo numérico asociado utilizando el MEF. Para la construcción del modelo de elementos finitos ha sido necesario construir un total de 20 secciones transversales de la cóclea para, después, poder transportarlos a ANSYS y realizar el modelo de EF. Dicho algoritmo se define semiautomático debido a que es necesaria la intervención humana para determinar el marco de interés, así como qué tomografías se van a utilizar para cada una de las secciones transversales, mientras el resto de los procesos los realiza de forma automática, tanto en MATLAB como en ANSYS. El desarrollo de este algoritmo ha sido una de las aportaciones originales de esta tesis, pues hasta la fecha no se ha desarrollado ningún modelo que permita el modelado automático de la geometría del oído interno. Por último, se ha realizado un análisis de la Energía Interna Absorbida por el oído interno para determinar la influencia de los diferentes elementos del SAH en la transferencia del sonido. Para ello se han estudiado tres modelos: uno compuesto por el canal auditivo externo (CAE) y la membrana timpánica (MT); un segundo, compuesto por el CAE, MT, cadena osicular (CO) y cóclea simplificada; y el tercero, compuesto por CAE, MT, CO y cóclea completa, obtenida por nuestro algoritmo. La obtención de la curva de Energía Absorbida ha conllevado el procesado de 3.285.080 datos

Understanding cognitive differences in processing competing visualizations of complex systems

Node-link diagrams are used represent systems having different elements and relationships among the elements. Representing the systems using visualizations like node-link diagrams provides cognitive aid to individuals in understanding the system and effectively managing these systems. Using appropriate visual tools aids in task completion by reducing the cognitive load of individuals in understanding the problems and solving them. However, the visualizations that are currently developed lack any cognitive processing based evaluation. Most of the evaluations (if any) are based on the result of tasks performed using these visualizations. Therefore, the evaluations do not provide any perspective from the point of the cognitive processing required in working with the visualization. This research focuses on understanding the effect of different visualization types and complexities on problem understanding and performance using a visual problem solving task. Two informationally equivalent but visually different visualizations - geon diagrams based on structural object perception theory and UML diagrams based on object modeling - are investigated to understand the cognitive processes that underlie reasoning with different types of visualizations. Specifically, the two visualizations are used to represent interdependent critical infrastructures. Participants are asked to solve a problem using the different visualizations. The effectiveness of the task completion is measured in terms of the time taken to complete the task and the accuracy of the result of the task. The differences in the cognitive processing while using the different visualizations are measured in terms of the search path and the search-steps of the individual. The results from this research underscore the difference in the effectiveness of the different diagrams in solving the same problem. The time taken to complete the task is significantly lower in geon diagrams. The error rate is also significantly lower when using geon diagrams. The search path for UML diagrams is more node-dominant but for geon diagrams is a distribution of nodes, links and components (combinations of nodes and links). Evaluation dominates the search-steps in geon diagrams whereas locating steps dominate UML diagrams. The results also show that the differences in search path and search steps for different visualizations increase when the complexity of the diagrams increase. This study helps to establish the importance of cognitive level understanding of the use of diagrammatic representation of information for visual problem solving. The results also highlight that measures of effectiveness of any visualization should include measuring the cognitive process of individuals while they are doing the visual task apart from the measures of time and accuracy of the result of a visual task

Un flujo de trabajo para la creación de modelos anatómicos del oído y los tejidos cerebrales en pacientes con implante coclear

El desarrollo de intervenciones de cirugía de oído presenta un desafío importante debido a la complejidad anatómica de las pequeñas estructuras internas y la variabilidad anatómica existente entre pacientes. El objetivo de este estudio es presentar un nuevo flujo de trabajo o pipeline para la creación de modelos anatómicos del oído y la cabeza del paciente para la simulación virtual de cirugías y la obtención sistemática de datos anatómicos y quirúrgicos de interés clínico. El flujo de trabajo propuesto, denominado OTOVIRT, comienza con el registro multimodal de imágenes de resonancia magnética (RM) y tomografía computarizada (TC) de los pacientes. Estas imágenes se alinean y se realizan segmentaciones de estructuras clave como el hueso temporal y la cóclea, para crear modelos tridimensionales de la anatomía de cada paciente. Para ello se han armonizado herramientas basadas en software de código abierto, simplificando y optimizando el soporte para el entrenamiento del personal médico. El flujo de OTOVIRT ha sido implementado y validado en un entorno clínico utilizando imágenes de pacientes candidatos para cirugías de implante coclear. Esta validación confirma la efectividad del enfoque propuesto y su capacidad para proporcionar una representación precisa de la anatomía de los pacientes, lo que puede ser de gran utilidad en la planificación y el análisis de cirugías de oído. En resumen, este estudio introduce un enfoque innovador para la simulación virtual de cirugías de oído y la generación de modelos 3D anatómicos personalizados.The performance of surgical interventions of the inner ear still poses significant challenges due to the complexity of the small internal structures and the anatomical variability between patients. This study proposes a new workflow or pipeline for developing individualized anatomical models of the ear and the head of the patient for virtual surgeries, as well as for the systematic collection of anatomical and surgical data. The proposed workflow, OTOVIRT, is based on the multimodal register of a patient’s computed tomography and magnetic resonance image (MRI). These images are subsequently co-aligned and relevant ear structures, such as the temporal bone and the cochlea, are segmented to create three-dimensional models of patient anatomy. To this end, the harmonization of available open-source software tools has been conducted in this work, with the objective of simplifying and optimizing the surgical training procedure of surgeons. OTOVIRT workflow has been implemented and validated in a clinical setting using CT and MR images of patients eligible for cochlear implant surgeries. Such a preliminary validation has allowed us to confirm the effectiveness of the proposed approach and its ability to provide an accurate representation of a patient`s anatomy. The pipeline developed has shown to be a useful tool in the planning and analysis of inner ear surgeries. In summary, this study introduces an innovative approach for the virtual simulation and the development of personalized anatomical 3D models of the inner ear and the head.Universidad de Sevilla. Máster en Ingeniería Industria

Doctor of Philosophy

dissertationFor many with severe-to-profound hearing loss, a condition in which the cochlea is unable to convert sound vibration into neural information to the brain, the cochlear implant has become the standard treatment. The goal of a cochlear-implant system is to bypass the malfunctioned cochlea and directly stimulate the nerves responsible for hearing through an array of electrodes on a silicone-elastomer carrier. However, the insertion of the electrode arrays can often cause intracochlear damage and eliminate residual hearing. With increased focus on hearing preservation in cochlear implantation, methods to minimize intracochlear damage have become a priority in electrode-array insertions. This dissertation explores the application of magnetic manipulation toward improved cochlear-implant electrode-array insertions. We start with initial 3-to-1 proof-of-concept experiments to demonstrate the feasibility of this approach. Then, to achieve relevancy at clinical scale, lateral-wall-type electrode-array models, used in the clinic, are slightly modified at the tip to include a tiny magnet. Next, a scala-tympani phantom is designed with both simulated cochleostomy and round-window openings to mimic both classes of insertions typically conducted. In particular, this is the first phantom to model a round-window opening and can be used reliably to simulate insertion forces in cadaver cochleae. Electrode arrays are then magnetically guided through these phantoms with a statistically significant (p < 0.05) reduction in insertion forces, and by as much as 50% for some electrode-array models. In particular, guiding the electrode-array tip through the cochlear hook and the basal turn, in the same insertion, was demonstrated for the first time using this technology. All existing methods to guide the electrode array can only be accomplished for the basal turn. Analysis is conducted to determine the optimal size and placement of a magnetic dipole-field source for use in the clinic. Its placement is determined to be consistently lateral to and anterior to the patient’s cochlea. Its size depends on numerous factors including the patient, torque requirements, and registration error. Sensitivity curves summarizing these factors are provided. The volume of the magnetic dipole-field source can be reduced by a factor of 5, on average, by moving it from the modiolar configuration originally proposed to this optimal configuration. We verify that magnetic forces do not pose any appreciable risk to the basilar membrane at the optimal configuration. Although patient-specific optimal configurations are characterized, a one-size-fits-all version is described that may be more practical and carries the benefit of substantial robustness to registration error

Three-dimensional modeling and visualization of the cochlea on the Internet.

Three-dimensional (3-D) modeling and visualization of the cochlea using the World Wide Web (WWW) is an effective way of sharing anatomic information for cochlear implantation over the Internet, particularly for morphometry-based research and resident training in otolaryngology and neuroradiology. In this paper, 3-D modeling, visualization, and animation techniques are integrated in an interactive and platform-independent manner and implemented over the WWW. Cohen's template shape with mean cross-sectional areas of the human cochlea is extended into a 3-D geometrical model. Also, spiral computer tomography data of a patient's cochlea is digitally segmented and geometrically represented. The cochlear electrode array is synthesized according to its specification. Then, cochlear implantation is animated with both idealized and real cochlear models. Insertion length, angular position, and characteristic frequency of individual electrodes are estimated online during the virtual insertion. The optimization of the processing parameters is done to demonstrate the feasibility of this technology for clinical applications.restrictio