IE-Map: a novel in-vivo atlas and template of the human inner ear

Brain atlases and templates are core tools in scientific research with increasing importance also in clinical applications. Advances in neuroimaging now allowed us to expand the atlas domain to the vestibular and auditory organ, the inner ear. In this study, we present IE-Map, an in-vivo template and atlas of the human labyrinth derived from multi-modal high-resolution magnetic resonance imaging (MRI) data, in a fully non-invasive manner without any contrast agent or radiation. We reconstructed a common template from 126 inner ears (63 normal subjects) and annotated it with 94 established landmarks and semi-automatic segmentations of all relevant macroscopic vestibular and auditory substructures. We validated the atlas by comparing MRI templates to a novel CT/micro-CT atlas, which we reconstructed from 21 publicly available post-mortem images of the bony labyrinth. Templates in MRI and micro-CT have a high overlap, and several key anatomical measures of the bony labyrinth in IE-Map are in line with micro-CT literature of the inner ear. A quantitative substructural analysis based on the new template, revealed a correlation of labyrinth parameters with total intracranial volume. No effects of gender or laterality were found. We provide the validated templates, atlas segmentations, surface meshes and landmark annotations as open-access material, to provide neuroscience researchers and clinicians in neurology, neurosurgery, and otorhinolaryngology with a widely applicable tool for computational neuro-otology

Automatic 3D segmentation of the prostate on magnetic resonance images for radiotherapy planning

Abstract. Accurate segmentation of the prostate, the seminal vesicles, the bladder and the rectum is a crucial step for planning radiotherapy (RT) procedures. Modern radiotherapy protocols have included the delineation of the pelvic organs in magnetic resonance images (MRI), as the guide to the therapeutic beam irradiation over the target organ. However, this task is highly inter and intra-expert variable and may take about 20 minutes per patient, even for trained experts, constituting an important burden in most radiological services. Automatic or semi-automatic segmentation strategies might then improve the efficiency by decreasing the measured times while conserving the required accuracy. This thesis presents a fully automatic prostate segmentation framework that selects the most similar prostates w.r.t. a test prostate image and combines them to estimate the segmentation for the test prostate. A robust multi-scale analysis establishes the set of most similar prostates from a database, independently of the acquisition protocol. Those prostates are then non-rigidly registered towards the test image and fusioned by a linear combination. The proposed approach was evaluated using a MRI public dataset of patients with benign hyperplasia or cancer, following different acquisition protocols, namely 26 endorectal and 24 external. Evaluating under a leave-one-out scheme, results show reliable segmentations, obtaining an average dice coefficient of 79%, when comparing with the expert manual segmentation.La delineación exacta de la próstata, las vesículas seminales, la vejiga y el recto es un paso fundamental para el planeamiento de procedimientos de radioterapia. Protocolos modernos han incluido la delineación de los órganos pélvicos en imágenes de resonancia magnética (IRM), como la guia para la irradiación del haz terapéutico sobre el órgano objetivo. Sin embargo, esta tarea es altamente variable intra e inter-experto y puede tomar al rededor de 20 minutos por paciente, incluso para expertos entrenados, convirtiéndose en una carga importante en la mayoría de los servicios de radiología. Métodos automáticos o semi-automáticos podrían mejorar la eficiencia disminuyendo los tiempos medidos mientras se conserva la precisión requerida. Este trabajo presenta una estrategia de segmentación de la próstata completamente automático que selecciona las prostatas más similares con respecto a una imagen de resonancia magnética de prueba y combina las delineaciones asociadas a dichas imágenes para estimar la segmentación de la imagen de prueba. Un análisis multiescala robusto permite establecer el conjunto de las próstatas más parecidas de una base de datos, independiente del protocolo de adquisición. Las imágenes seleccionadas son registradas de forma no rigida con respecto a la imagen de prueba y luego son fusionadas mediante una combinación lineal. El enfoque propuesto fue evaluado utilizando un conjunto público de imágenes de resonancia magnética de pacientes con hiperplasia benigna o con cancer, con diferentes protocolos de adquisición, esto es 26 externas y 24 endorectales. Este trabajo fue evaluado bajo un esquema leave-one-out, cuyos resultados mostraron segmentaciones confiables, obteniendo un DSC promedio de 79%, cuando se compararon los resultados obtenidos con las segmentaciones manuales de expertos.Maestrí

Correlated Multimodal Imaging in Life Sciences:Expanding the Biomedical Horizon

International audienceThe frontiers of bioimaging are currently being pushed toward the integration and correlation of several modalities to tackle biomedical research questions holistically and across multiple scales. Correlated Multimodal Imaging (CMI) gathers information about exactly the same specimen with two or more complementary modalities that-in combination-create a composite and complementary view of the sample (including insights into structure, function, dynamics and molecular composition). CMI allows to describe biomedical processes within their overall spatio-temporal context and gain a mechanistic understanding of cells, tissues, diseases or organisms by untangling their molecular mechanisms within their native environment. The two best-established CMI implementations for small animals and model organisms are hardware-fused platforms in preclinical imaging (Hybrid Imaging) and Correlated Light and Electron Microscopy (CLEM) in biological imaging. Although the merits of Preclinical Hybrid Imaging (PHI) and CLEM are well-established, both approaches would benefit from standardization of protocols, ontologies and data handling, and the development of optimized and advanced implementations. Specifically, CMI pipelines that aim at bridging preclinical and biological imaging beyond CLEM and PHI are rare but bear great potential to substantially advance both bioimaging and biomedical research. CMI faces three mai

Articulated Statistical Shape Modelling of the Shoulder Joint

The shoulder joint is the most mobile and unstable joint in the human body. This makes it vulnerable to soft tissue pathologies and dislocation. Insight into the kinematics of the joint may enable improved diagnosis and treatment of different shoulder pathologies. Shoulder joint kinematics can be influenced by the articular geometry of the joint. The aim of this project was to develop an analysis framework for shoulder joint kinematics via the use of articulated statistical shape models (ASSMs). Articulated statistical shape models extend conventional statistical shape models by combining the shape variability of anatomical objects collected from different subjects (statistical shape models), with the physical variation of pose between the same objects (articulation). The developed pipeline involved manual annotation of anatomical landmarks selected on 3D surface meshes of scapulae and humeri and establishing dense surface correspondence across these data through a registration process. The registration was performed using a Gaussian process morphable model fitting approach. In order to register two objects separately, while keeping their shape and kinematics relationship intact, one of the objects (scapula) was fixed leaving the other (humerus) to be mobile. All the pairs of registered humeri and scapulae were brought back to their native imaged position using the inverse of the associated registration transformation. The glenohumeral rotational center and local anatomic coordinate system of the humeri and scapulae were determined using the definitions suggested by the International Society of Biomechanics. Three motions (flexion, abduction, and internal rotation) were generated using Euler angle sequences. The ASSM of the model was built using principal component analysis and validated. The validation results show that the model adequately estimated the shape and pose encoded in the training data. Developing ASSM of the shoulder joint helps to define the statistical shape and pose parameters of the gleno humeral articulating surfaces. An ASSM of the shoulder joint has potential applications in the analysis and investigation of population-wide joint posture variation and kinematics. Such analyses may include determining and quantifying abnormal articulation of the joint based on the range of motion; understanding of detailed glenohumeral joint function and internal joint measurement; and diagnosis of shoulder pathologies. Future work will involve developing a protocol for encoding the shoulder ASSM with real, rather than handcrafted, pose variation

Novel Approaches to the Representation and Analysis of 3D Segmented Anatomical Districts

Nowadays, image processing and 3D shape analysis are an integral part of clinical practice and have the potentiality to support clinicians with advanced analysis and visualization techniques. Both approaches provide visual and quantitative information to medical practitioners, even if from different points of view. Indeed, shape analysis is aimed at studying the morphology of anatomical structures, while image processing is focused more on the tissue or functional information provided by the pixels/voxels intensities levels. Despite the progress obtained by research in both fields, a junction between these two complementary worlds is missing. When working with 3D models analyzing shape features, the information of the volume surrounding the structure is lost, since a segmentation process is needed to obtain the 3D shape model; however, the 3D nature of the anatomical structure is represented explicitly. With volume images, instead, the tissue information related to the imaged volume is the core of the analysis, while the shape and morphology of the structure are just implicitly represented, thus not clear enough. The aim of this Thesis work is the integration of these two approaches in order to increase the amount of information available for physicians, allowing a more accurate analysis of each patient. An augmented visualization tool able to provide information on both the anatomical structure shape and the surrounding volume through a hybrid representation, could reduce the gap between the two approaches and provide a more complete anatomical rendering of the subject. To this end, given a segmented anatomical district, we propose a novel mapping of volumetric data onto the segmented surface. The grey-levels of the image voxels are mapped through a volume-surface correspondence map, which defines a grey-level texture on the segmented surface. The resulting texture mapping is coherent to the local morphology of the segmented anatomical structure and provides an enhanced visual representation of the anatomical district. The integration of volume-based and surface-based information in a unique 3D representation also supports the identification and characterization of morphological landmarks and pathology evaluations. The main research contributions of the Ph.D. activities and Thesis are: \u2022 the development of a novel integration algorithm that combines surface-based (segmented 3D anatomical structure meshes) and volume-based (MRI volumes) information. The integration supports different criteria for the grey-levels mapping onto the segmented surface; \u2022 the development of methodological approaches for using the grey-levels mapping together with morphological analysis. The final goal is to solve problems in real clinical tasks, such as the identification of (patient-specific) ligament insertion sites on bones from segmented MR images, the characterization of the local morphology of bones/tissues, the early diagnosis, classification, and monitoring of muscle-skeletal pathologies; \u2022 the analysis of segmentation procedures, with a focus on the tissue classification process, in order to reduce operator dependency and to overcome the absence of a real gold standard for the evaluation of automatic segmentations; \u2022 the evaluation and comparison of (unsupervised) segmentation methods, finalized to define a novel segmentation method for low-field MR images, and for the local correction/improvement of a given segmentation. The proposed method is simple but effectively integrates information derived from medical image analysis and 3D shape analysis. Moreover, the algorithm is general enough to be applied to different anatomical districts independently of the segmentation method, imaging techniques (such as CT), or image resolution. The volume information can be integrated easily in different shape analysis applications, taking into consideration not only the morphology of the input shape but also the real context in which it is inserted, to solve clinical tasks. The results obtained by this combined analysis have been evaluated through statistical analysis

Multimodal image analysis of the human brain

Gedurende de laatste decennia heeft de snelle ontwikkeling van multi-modale en niet-invasieve hersenbeeldvorming technologieën een revolutie teweeg gebracht in de mogelijkheid om de structuur en functionaliteit van de hersens te bestuderen. Er is grote vooruitgang geboekt in het beoordelen van hersenschade door gebruik te maken van Magnetic Reconance Imaging (MRI), terwijl Elektroencefalografie (EEG) beschouwd wordt als de gouden standaard voor diagnose van neurologische afwijkingen. In deze thesis focussen we op de ontwikkeling van nieuwe technieken voor multi-modale beeldanalyse van het menselijke brein, waaronder MRI segmentatie en EEG bronlokalisatie. Hierdoor voegen we theorie en praktijk samen waarbij we focussen op twee medische applicaties: (1) automatische 3D MRI segmentatie van de volwassen hersens en (2) multi-modale EEG-MRI data analyse van de hersens van een pasgeborene met perinatale hersenschade. We besteden veel aandacht aan de verbetering en ontwikkeling van nieuwe methoden voor accurate en ruisrobuuste beeldsegmentatie, dewelke daarna succesvol gebruikt worden voor de segmentatie van hersens in MRI van zowel volwassen als pasgeborenen. Daarenboven ontwikkelden we een geïntegreerd multi-modaal methode voor de EEG bronlokalisatie in de hersenen van een pasgeborene. Deze lokalisatie wordt gebruikt voor de vergelijkende studie tussen een EEG aanval bij pasgeborenen en acute perinatale hersenletsels zichtbaar in MRI

AUGMENTED REALITY AND INTRAOPERATIVE C-ARM CONE-BEAM COMPUTED TOMOGRAPHY FOR IMAGE-GUIDED ROBOTIC SURGERY

Minimally-invasive robotic-assisted surgery is a rapidly-growing alternative to traditionally open and laparoscopic procedures; nevertheless, challenges remain. Standard of care derives surgical strategies from preoperative volumetric data (i.e., computed tomography (CT) and magnetic resonance (MR) images) that benefit from the ability of multiple modalities to delineate different anatomical boundaries. However, preoperative images may not reflect a possibly highly deformed perioperative setup or intraoperative deformation. Additionally, in current clinical practice, the correspondence of preoperative plans to the surgical scene is conducted as a mental exercise; thus, the accuracy of this practice is highly dependent on the surgeon’s experience and therefore subject to inconsistencies. In order to address these fundamental limitations in minimally-invasive robotic surgery, this dissertation combines a high-end robotic C-arm imaging system and a modern robotic surgical platform as an integrated intraoperative image-guided system. We performed deformable registration of preoperative plans to a perioperative cone-beam computed tomography (CBCT), acquired after the patient is positioned for intervention. From the registered surgical plans, we overlaid critical information onto the primary intraoperative visual source, the robotic endoscope, by using augmented reality. Guidance afforded by this system not only uses augmented reality to fuse virtual medical information, but also provides tool localization and other dynamic intraoperative updated behavior in order to present enhanced depth feedback and information to the surgeon. These techniques in guided robotic surgery required a streamlined approach to creating intuitive and effective human-machine interferences, especially in visualization. Our software design principles create an inherently information-driven modular architecture incorporating robotics and intraoperative imaging through augmented reality. The system's performance is evaluated using phantoms and preclinical in-vivo experiments for multiple applications, including transoral robotic surgery, robot-assisted thoracic interventions, and cocheostomy for cochlear implantation. The resulting functionality, proposed architecture, and implemented methodologies can be further generalized to other C-arm-based image guidance for additional extensions in robotic surgery

Registration of medical images for applications in minimally invasive procedures

Il punto di partenza di questa tesi \ue8 l'analisi dei metodi allo stato dell'arte di registrazione delle immagini mediche per verificare se sono adatti ad essere utilizzati per assistere il medico durante una procedura minimamente invasiva , ad esempio una procedura percutanea eseguita manualmente o un intervento teleoperato eseguito per mezzo di un robot . La prima conclusione \ue8 che, anche se ci sono tanti lavori dedicati allo sviluppo di algoritmi di registrazione da applicare nel contesto medico, la maggior parte di essi non sono stati progettati per essere utilizzati nello scenario della sala operatoria (OR) anche perch\ue9, rispetto ad altre applicazioni , OR richiede anche la validazione, prestazioni in tempo reale e la presenza di altri strumenti . Gli algoritmi allo stato dell'arte sono basati su un iterazione in tre fasi : ottimizzazione - trasformazione - valutazione della somiglianza delle immagini registrate. In questa tesi, studiamo la fattibilit\ue0 dell'approccio in tre fasi per applicazioni OR, mostrando i limiti che tale approccio incontra nelle applicazioni che stiamo considerando. Verr\ue0 dimostrato come un metodo semplice si potrebbe utilizzare nella OR. Abbiamo poi sviluppato una teoria che \ue8 adatta a registrare grandi insiemi di dati non strutturati estratti da immagini mediche, tenendo conto dei vincoli della OR . Vista l'impossibilit\ue0 di lavorare con dati medici di tipo DICOM, verr\ue0 impiegato un metodo per registrare dataset composti da insiemi di punti non strutturati. Gli algoritmi proposti sono progettati per trovare la corrispondenza spaziale in forma chiusa tenendo conto del tipo di dati, il vincolo del tempo e la presenza di rumore e /o piccole deformazioni. La teoria e gli algoritmi che abbiamo sviluppato sono derivati dalla teoria delle forme proposta da Kendall (Kendall's shapes) e utilizza un descrittore globale della forma per calcolare le corrispondenze e la distanza tra le strutture coinvolte . Poich\ue9 la registrazione \ue8 solo una componente nelle applicazioni mediche, l' ultima parte della tesi \ue8 dedicata ad alcune applicazioni pratiche in OR che possono beneficiare della procedura di registrazione .The registration of medical images is necessary to establish spatial correspondences across two or more images. Registration is rarely the end-goal, but instead, the results of image registration are used in other tasks. The starting point of this thesis is to analyze which methods at the state of the art of image registration are suitable to be used in assisting a physician during a minimally invasive procedure, such as a percutaneous procedure performed manually or a teleoperated intervention performed by the means of a robot. The first conclusion is that, even if much previous work has been devoted to develop registration algorithms to be applied in the medical context, most of them are not designed to be used in the operating room scenario (OR) because, compared to other applications, the OR requires also a strong validation, real-time performance and the presence of other instruments. Almost all of these algorithms are based on a three phase iteration: optimize-transform-evaluate similarity. In this thesis, we study the feasibility of this three steps approach in the OR, showing the limits that such approach encounter in the applications we are considering. We investigate how could a simple method be realizable and what are the assumptions for such a method to work. We then develop a theory that is suitable to register large sets of unstructured data extracted from medical images keeping into account the constraints of the OR. The use of the whole radiologic information is not feasible in the OR context, therefore the method we are introducing registers processed dataset extracted from the original medical images. The framework we propose is designed to find the spatial correspondence in closed form keeping into account the type of the data, the real-time constraint and the presence of noise and/or small deformations. The theory and algorithms we have developed are in the framework of the shape theory proposed by Kendall (Kendall's shapes) and uses a global descriptor of the shape to compute the correspondences and the distance between shapes. Since the registration is only a component of a medical application, the last part of the thesis is dedicated to some practical applications in the OR that can benefit from the registration procedure

Reconstruction 3D personnalisée de la colonne vertébrale à partir d'images radiographiques non-calibrées

Les systèmes de reconstruction stéréo-radiographique 3D -- La colonne vertébrale -- La scoliose idiopathique adolescente -- Évolution des systèmes de reconstruction 3D -- Filtres de rehaussement d'images -- Techniques de segmentation -- Les méthodes de calibrage -- Les méthodes de reconstruction 3D -- Problématique, hypothèses, objectifs et méthode générale -- Three-dimensional reconstruction of the scoliotic spine and pelvis from uncalibrated biplanar X-ray images -- A versatile 3D reconstruction system of the spine and pelvis for clinical assessment of spinal deformities -- Simulation experiments -- Clinical validation -- A three-dimensional retrospective analysis of the evolution of spinal instrumentation for the correction of adolescent idiopathic scoliosis -- Auto-calibrage d'un système à rayons-X à partir de primitives de haut niveau -- Segmentation de la colonne vertébrale -- Approche hiérarchique d'auto-calibrage d'un système d'acquisition à rayons-X -- Personalized 3D reconstruction of the scoliotic spine from hybrid statistical and X-ray image-based models -- Validation protocol