Automating the multimodal analysis of musculoskeletal imaging in the presence of hip implants

In patients treated with hip arthroplasty, the muscular condition and presence of inflammatory reactions are assessed using magnetic resonance imaging (MRI). As MRI lacks contrast for bony structures, computed tomography (CT) is preferred for clinical evaluation of bone tissue and orthopaedic surgical planning. Combining the complementary information of MRI and CT could improve current clinical practice for diagnosis, monitoring and treatment planning. In particular, the different contrast of these modalities could help better quantify the presence of fatty infiltration to characterise muscular condition after hip replacement. In this thesis, I developed automated processing tools for the joint analysis of CT and MR images of patients with hip implants. In order to combine the multimodal information, a novel nonlinear registration algorithm was introduced, which imposes rigidity constraints on bony structures to ensure realistic deformation. I implemented and thoroughly validated a fully automated framework for the multimodal segmentation of healthy and pathological musculoskeletal structures, as well as implants. This framework combines the proposed registration algorithm with tailored image quality enhancement techniques and a multi-atlas-based segmentation approach, providing robustness against the large population anatomical variability and the presence of noise and artefacts in the images. The automation of muscle segmentation enabled the derivation of a measure of fatty infiltration, the Intramuscular Fat Fraction, useful to characterise the presence of muscle atrophy. The proposed imaging biomarker was shown to strongly correlate with the atrophy radiological score currently used in clinical practice. Finally, a preliminary work on multimodal metal artefact reduction, using an unsupervised deep learning strategy, showed promise for improving the postprocessing of CT and MR images heavily corrupted by metal artefact. This work represents a step forward towards the automation of image analysis in hip arthroplasty, supporting and quantitatively informing the decision-making process about patient’s management

Individualised Clinical Neuroimaging in the Developing Brain: Abnormality Detection

Perinatal neuroanatomical structure is incredibly intricate and, at time of birth, is undergoing continuous change due to interweaving developmental processes (growth, myelination and gyrification). While there is some small variability in structure and rates of development, all follow proscribed pathways with well documented milestones. Brain injury or other disruption of these processes can result in poor neurodevelopmental outcomes or mortality, making their early identification critical to estimate, and potentially forestall, negative effects. MRI is an increasingly used method of investigating suspected neonatal encephalopathies and injuries.Identification of these injuries and malformations is more challenging in neonates compared to adults due to the brain’s continuously evolving appearance. This makes radiological review of neonatal MRI an intensive and time-consuming task which, in an ideal setting, requires a team of highly skilled clinicians and radiologists with complementary training and extensive experience. To assist this review process, some localisation method that highlights areas likely to contain tissue abnormalities would be highly desirable, as it could quickly draw attention to these locations. In addition, identifying neonates whose MRI is likely to contain some form of pathology could allow for review prioritisation.In this thesis, I first investigated using normative models of neonatal tissue intensity for brain tissue abnormality detection. I applied voxel-wise Gaussian process (GP) regression to a training cohort of neonates with no obvious lesions, all born preterm (<37 weeks) but imaged between 28-55 weeks. Gestational age at birth (GA), postmenstrual age at scan (PMA) and sex were used as input variables and voxel intensity as the output variable. GPs output a mean value and its variance inferred from neonates within the training cohort whose demographic information most closely matched those of the prediction target. The voxel specific models were put together to form a synthesised typical image and standard deviation image derived from the variance outputs. Z-score abnormality maps were constructed by taking the difference between neonates actual MRI and GP-calculated synthetic image and scaling by their standard deviation map. Higher Z-score map values indicate voxels more likely to contain abnormal tissue intensity. Using manually delineated masks of common brain injuries seen in a subset of neonates, these abnormality Z-score maps demonstrated good detection performance using area under the curve of receiver operating characteristic scores, with the exception of small punctate lesions.The initial voxel-wise models had substantial false positives around the edges of the brain where there is large typical heterogeneity. I next investigated if incorporating local structural information into predictive models could improve their ability to accommodate typical anatomical heterogeneity seen across individual brains and improve the accuracy of synthetic images and abnormality detection. To achieve this, voxel intensity values in a patch surrounding the prediction target were appended to the design matrix, alongside GMA, PMA and sex. The patch-based synthetic images were able to match an individual’s brain structure more closely and had lower false positives in normal appearing tissue. However, a weakness was that the centre of some larger lesions was included in the predictions (thereby classified as ‘healthy’ tissue), having a deleterious effect on their coverage, increasing false negatives. This was offset by much better coverage of smaller, more subtle lesions, to the extent that overall performance was higher compared to that seen in the earlier model.I also investigated if the Z-score abnormality maps could be used to classify neonates with MRI positive brain injury from those with normal appearing brains. While many machine learning algorism see frequent use in neuroimaging classification tasks, I opted for a logistic regression model due to its high levels of interpretability and simple implementation. Using the histograms of the Z-score abnormality maps as inputs, the model demonstrated good performance, being able to correctly identify neonates with injuries, but not those with subtle lesions like punctate lesions, whilst minimising false identification of neonates with normal appearing brains.To ascertain if performance could be improved, I explored multiple classification methods. Specifically, the use of other more complex classifiers (random forest, support vector machines, GP classification) and the use of a regional abnormal voxel count, that allowed localisation of lesioned tissue rather than the more global detection ability of the Z-score histograms. Using these innovations, I investigated their application towards a specific pathology; hypoxic ischemic encephalopathy (HIE). This is a good test for the system, as HIE has high incidence rates, multiple associated lesion types and a time dependant appearance. Further, I wanted to know if, given a positive HIE diagnosis, the Z-score abnormality maps could be used to predict long-term outcomes (normal vs poor). Several models demonstrated an excellent ability to separate HIE and healthy control neonates achieving >90% accuracy, a statistically significant result even after false discovery rate (FDR) correction (p-value < 0.05). While the outcome prediction models achieved reasonable accuracy, >70% in multiple models, none of these were statistically significant after FDR correction.Overall, this work demonstrates how normative modelling can be used to create individual voxel-wise / image-wise estimation of tissue abnormality for neonatal MRI across a range of gestational ages. It further demonstrates that these abnormality maps can be utilised for additional tasks, in this instance, three increasingly challenging neurological classification problems. These include the separation of neonates with and without MRI positive lesions, identification of neonates with a specific pathological condition (HIE) and prediction of long-term functional outcome (normal vs poor). Within a radiological setting, these classifications task can be considered analogous to three radiological challenges, image triage, diagnostic detection and estimation of developmental prognosis, important for the clinical team but also infants and their families

Signs of progression:MR image analysis for the management of low-grade glioma

Every year approximately one thousand people in the Netherlands are diagnosedwith diffuse glioma, a type of infiltrative brain tumor that originates from theglial cells. There is no curative treatment available for adults diagnosed witha diffuse glioma, although surgical resection, radiotherapy and chemotherapyare used to improve prognosis and decrease symptoms. Low-grade glioma canremain stable for long periods of time before, inevitably, malignant progressionoccurs. The radiological assessment of glioma through magnetic resonanceimaging (MRI) plays an important role in the management of glioma. Inthis thesis I explore the role of quantitative measurements, emerging imagingmarkers and predictive modelling in the management of glioma. These methodscan aid the radiologist to predict the timing, location and severity of tumorprogression, to ultimately improve the quality of life for glioma patients.<br/

Automated template-based brain localization and extraction for fetal brain MRI reconstruction.

Most fetal brain MRI reconstruction algorithms rely only on brain tissue-relevant voxels of low-resolution (LR) images to enhance the quality of inter-slice motion correction and image reconstruction. Consequently the fetal brain needs to be localized and extracted as a first step, which is usually a laborious and time consuming manual or semi-automatic task. We have proposed in this work to use age-matched template images as prior knowledge to automatize brain localization and extraction. This has been achieved through a novel automatic brain localization and extraction method based on robust template-to-slice block matching and deformable slice-to-template registration. Our template-based approach has also enabled the reconstruction of fetal brain images in standard radiological anatomical planes in a common coordinate space. We have integrated this approach into our new reconstruction pipeline that involves intensity normalization, inter-slice motion correction, and super-resolution (SR) reconstruction. To this end we have adopted a novel approach based on projection of every slice of the LR brain masks into the template space using a fusion strategy. This has enabled the refinement of brain masks in the LR images at each motion correction iteration. The overall brain localization and extraction algorithm has shown to produce brain masks that are very close to manually drawn brain masks, showing an average Dice overlap measure of 94.5%. We have also demonstrated that adopting a slice-to-template registration and propagation of the brain mask slice-by-slice leads to a significant improvement in brain extraction performance compared to global rigid brain extraction and consequently in the quality of the final reconstructed images. Ratings performed by two expert observers show that the proposed pipeline can achieve similar reconstruction quality to reference reconstruction based on manual slice-by-slice brain extraction. The proposed brain mask refinement and reconstruction method has shown to provide promising results in automatic fetal brain MRI segmentation and volumetry in 26 fetuses with gestational age range of 23 to 38 weeks

IMAGE PROCESSING, SEGMENTATION AND MACHINE LEARNING MODELS TO CLASSIFY AND DELINEATE TUMOR VOLUMES TO SUPPORT MEDICAL DECISION

Techniques for processing and analysing images and medical data have become the main’s translational applications and researches in clinical and pre-clinical environments. The advantages of these techniques are the improvement of diagnosis accuracy and the assessment of treatment response by means of quantitative biomarkers in an efficient way. In the era of the personalized medicine, an early and efficacy prediction of therapy response in patients is still a critical issue. In radiation therapy planning, Magnetic Resonance Imaging (MRI) provides high quality detailed images and excellent soft-tissue contrast, while Computerized Tomography (CT) images provides attenuation maps and very good hard-tissue contrast. In this context, Positron Emission Tomography (PET) is a non-invasive imaging technique which has the advantage, over morphological imaging techniques, of providing functional information about the patient’s disease. In the last few years, several criteria to assess therapy response in oncological patients have been proposed, ranging from anatomical to functional assessments. Changes in tumour size are not necessarily correlated with changes in tumour viability and outcome. In addition, morphological changes resulting from therapy occur slower than functional changes. Inclusion of PET images in radiotherapy protocols is desirable because it is predictive of treatment response and provides crucial information to accurately target the oncological lesion and to escalate the radiation dose without increasing normal tissue injury. For this reason, PET may be used for improving the Planning Treatment Volume (PTV). Nevertheless, due to the nature of PET images (low spatial resolution, high noise and weak boundary), metabolic image processing is a critical task. The aim of this Ph.D thesis is to develope smart methodologies applied to the medical imaging field to analyse different kind of problematic related to medical images and data analysis, working closely to radiologist physicians. Various issues in clinical environment have been addressed and a certain amount of improvements has been produced in various fields, such as organs and tissues segmentation and classification to delineate tumors volume using meshing learning techniques to support medical decision. In particular, the following topics have been object of this study: • Technique for Crohn’s Disease Classification using Kernel Support Vector Machine Based; • Automatic Multi-Seed Detection For MR Breast Image Segmentation; • Tissue Classification in PET Oncological Studies; • KSVM-Based System for the Definition, Validation and Identification of the Incisinal Hernia Reccurence Risk Factors; • A smart and operator independent system to delineate tumours in Positron Emission Tomography scans; 3 • Active Contour Algorithm with Discriminant Analysis for Delineating Tumors in Positron Emission Tomography; • K-Nearest Neighbor driving Active Contours to Delineate Biological Tumor Volumes; • Tissue Classification to Support Local Active Delineation of Brain Tumors; • A fully automatic system of Positron Emission Tomography Study segmentation. This work has been developed in collaboration with the medical staff and colleagues at the: • Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi (DIBIMED), University of Palermo • Cannizzaro Hospital of Catania • Istituto di Bioimmagini e Fisiologia Molecolare (IBFM) Centro Nazionale delle Ricerche (CNR) of Cefalù • School of Electrical and Computer Engineering at Georgia Institute of Technology The proposed contributions have produced scientific publications in indexed computer science and medical journals and conferences. They are very useful in terms of PET and MRI image segmentation and may be used daily as a Medical Decision Support Systems to enhance the current methodology performed by healthcare operators in radiotherapy treatments. The future developments of this research concern the integration of data acquired by image analysis with the managing and processing of big data coming from a wide kind of heterogeneous sources

Semiautomated 3D liver segmentation using computed tomography and magnetic resonance imaging

Le foie est un organe vital ayant une capacité de régénération exceptionnelle et un rôle crucial dans le fonctionnement de l’organisme. L’évaluation du volume du foie est un outil important pouvant être utilisé comme marqueur biologique de sévérité de maladies hépatiques. La volumétrie du foie est indiquée avant les hépatectomies majeures, l’embolisation de la veine porte et la transplantation. La méthode la plus répandue sur la base d'examens de tomodensitométrie (TDM) et d'imagerie par résonance magnétique (IRM) consiste à délimiter le contour du foie sur plusieurs coupes consécutives, un processus appelé la «segmentation». Nous présentons la conception et la stratégie de validation pour une méthode de segmentation semi-automatisée développée à notre institution. Notre méthode représente une approche basée sur un modèle utilisant l’interpolation variationnelle de forme ainsi que l’optimisation de maillages de Laplace. La méthode a été conçue afin d’être compatible avec la TDM ainsi que l' IRM. Nous avons évalué la répétabilité, la fiabilité ainsi que l’efficacité de notre méthode semi-automatisée de segmentation avec deux études transversales conçues rétrospectivement. Les résultats de nos études de validation suggèrent que la méthode de segmentation confère une fiabilité et répétabilité comparables à la segmentation manuelle. De plus, cette méthode diminue de façon significative le temps d’interaction, la rendant ainsi adaptée à la pratique clinique courante. D’autres études pourraient incorporer la volumétrie afin de déterminer des marqueurs biologiques de maladie hépatique basés sur le volume tels que la présence de stéatose, de fer, ou encore la mesure de fibrose par unité de volume.The liver is a vital abdominal organ known for its remarkable regenerative capacity and fundamental role in organism viability. Assessment of liver volume is an important tool which physicians use as a biomarker of disease severity. Liver volumetry is clinically indicated prior to major hepatectomy, portal vein embolization and transplantation. The most popular method to determine liver volume from computed tomography (CT) and magnetic resonance imaging (MRI) examinations involves contouring the liver on consecutive imaging slices, a process called “segmentation”. Segmentation can be performed either manually or in an automated fashion. We present the design concept and validation strategy for an innovative semiautomated liver segmentation method developed at our institution. Our method represents a model-based approach using variational shape interpolation and Laplacian mesh optimization techniques. It is independent of training data, requires limited user interactions and is robust to a variety of pathological cases. Further, it was designed for compatibility with both CT and MRI examinations. We evaluated the repeatability, agreement and efficiency of our semiautomated method in two retrospective cross-sectional studies. The results of our validation studies suggest that semiautomated liver segmentation can provide strong agreement and repeatability when compared to manual segmentation. Further, segmentation automation significantly shortens interaction time, thus making it suitable for daily clinical practice. Future studies may incorporate liver volumetry to determine volume-averaged biomarkers of liver disease, such as such as fat, iron or fibrosis measurements per unit volume. Segmental volumetry could also be assessed based on subsegmentation of vascular anatomy

Cloud-Based Benchmarking of Medical Image Analysis

Medical imagin

Traitement et exploration d'images TDM pour l'évaluation des bioprothèses valvulaires aortiques

Le but de cette étude est d évaluer la faisabilité de l analyse tomodensitométrique 3D des bioprothèses aortiques pour faciliter leur évaluation morphologique durant le suivi et d aider la sélection de cas et améliorer la planification d une procédure valvein-valve. Le challenge était représenté par le rehaussement des feuillets valvulaires, en raison d images très bruitées. Un angio-scanner synchronisé était réalisé chez des patients porteurs d une bioprotèses aortique dégénérée avant réintervention (images in-vivo). Différentes méthodes pour la réduction du bruit étaient proposées. La reconstruction tridimensionnelle des bioprothèses était réalisée en utilisant des méthodes de segmentation de régions par "sticks". Après réopération ces méthodes étaient appliquées aux images scanner des bioprothèses explantées (images ex-vivo) et utilisées comme référence. La réduction du bruit obtenue par le filtre stick modifié montrait meilleurs résultats en rapport signal/bruit en comparaison aux filtres de diffusion anisotropique. Toutes les méthodes de segmentation ont permis une reconstruction 3D des feuillets. L analyse qualitative a montré une bonne concordance entre les images obtenues in-vivo et les altérations des bioprothèses. Les résultats des différentes méthodes étaient comparés par critères volumétriques et discutés. Les bases d'une première approche de visualisation spatio-temporelle d'images TDM 3D+T de la prothèse valvulaire ont été proposés. Elle implique des techniques de rendu volumique et de compensation de mouvement. Son application à la valve native a aussi été envisagée. Les images scanner des bioprothèses aortiques nécessitent un traitement de débruitage et de réduction des artéfacts de façon à permettre le rehaussement des feuillets prothétiques. Les méthodes basées sticks semblent constituer une approche pertinente pour caractériser morphologiquement la dégénérescence des bioprothèses.The aim of the study was to assess the feasibility of CT based 3D analysis of degenerated aortic bioprostheses to make easier their morphological assessment. This could be helpful during regular follow-up and for case selection, improved planning and mapping of valve-in-valve procedure. The challenge was represented by leaflets enhancement because of highly noised CT images. Contrast-enhanced ECG-gated CT scan was performed in patients with degenerated aortic bioprostheses before reoperation (in-vivo images). Different methods for noise reduction were tested and proposed. 3D reconstruction of bioprostheses components was achieved using stick based region segmentation methods. After reoperation, segmentation methods were applied to CT images of the explanted prostheses (exvivo images). Noise reduction obtained by improved stick filter showed best results in terms of signal to noise ratio comparing to anisotropic diffusion filters. All segmentation methods applied to the best phase of in-vivo images allowed 3D bioprosthetic leaflets reconstruction. Explanted bioprostheses CT images were also processed and used as reference. Qualitative analysis revealed a good concordance between the in-vivo images and the bioprostheses alterations. Results from different methods were compared by means of volumetric criteria and discussed. A first approach for spatiotemporal visualization of 3D+T images of valve bioprosthesis has been proposed. Volume rendering and motion compensation techniques were applied to visualize different phases of CT data. Native valve was also considered. ECG-gated CT images of aortic bioprostheses need a preprocessing to reduce noise and artifacts in order to enhance prosthetic leaflets. Stick based methods seems to provide an interesting approach for the morphological characterization of degenerated bioprostheses.RENNES1-Bibl. électronique (352382106) / SudocSudocFranceF

Traitement et exploration d'images TDM pour l'évaluation des bioprothèses valvulaires aortiques

Le but de cette étude est d évaluer la faisabilité de l analyse tomodensitométrique 3D des bioprothèses aortiques pour faciliter leur évaluation morphologique durant le suivi et d aider la sélection de cas et améliorer la planification d une procédure valvein-valve. Le challenge était représenté par le rehaussement des feuillets valvulaires, en raison d images très bruitées. Un angio-scanner synchronisé était réalisé chez des patients porteurs d une bioprotèses aortique dégénérée avant réintervention (images in-vivo). Différentes méthodes pour la réduction du bruit étaient proposées. La reconstruction tridimensionnelle des bioprothèses était réalisée en utilisant des méthodes de segmentation de régions par "sticks". Après réopération ces méthodes étaient appliquées aux images scanner des bioprothèses explantées (images ex-vivo) et utilisées comme référence. La réduction du bruit obtenue par le filtre stick modifié montrait meilleurs résultats en rapport signal/bruit en comparaison aux filtres de diffusion anisotropique. Toutes les méthodes de segmentation ont permis une reconstruction 3D des feuillets. L analyse qualitative a montré une bonne concordance entre les images obtenues in-vivo et les altérations des bioprothèses. Les résultats des différentes méthodes étaient comparés par critères volumétriques et discutés. Les bases d'une première approche de visualisation spatio-temporelle d'images TDM 3D+T de la prothèse valvulaire ont été proposés. Elle implique des techniques de rendu volumique et de compensation de mouvement. Son application à la valve native a aussi été envisagée. Les images scanner des bioprothèses aortiques nécessitent un traitement de débruitage et de réduction des artéfacts de façon à permettre le rehaussement des feuillets prothétiques. Les méthodes basées sticks semblent constituer une approche pertinente pour caractériser morphologiquement la dégénérescence des bioprothèses.The aim of the study was to assess the feasibility of CT based 3D analysis of degenerated aortic bioprostheses to make easier their morphological assessment. This could be helpful during regular follow-up and for case selection, improved planning and mapping of valve-in-valve procedure. The challenge was represented by leaflets enhancement because of highly noised CT images. Contrast-enhanced ECG-gated CT scan was performed in patients with degenerated aortic bioprostheses before reoperation (in-vivo images). Different methods for noise reduction were tested and proposed. 3D reconstruction of bioprostheses components was achieved using stick based region segmentation methods. After reoperation, segmentation methods were applied to CT images of the explanted prostheses (exvivo images). Noise reduction obtained by improved stick filter showed best results in terms of signal to noise ratio comparing to anisotropic diffusion filters. All segmentation methods applied to the best phase of in-vivo images allowed 3D bioprosthetic leaflets reconstruction. Explanted bioprostheses CT images were also processed and used as reference. Qualitative analysis revealed a good concordance between the in-vivo images and the bioprostheses alterations. Results from different methods were compared by means of volumetric criteria and discussed. A first approach for spatiotemporal visualization of 3D+T images of valve bioprosthesis has been proposed. Volume rendering and motion compensation techniques were applied to visualize different phases of CT data. Native valve was also considered. ECG-gated CT images of aortic bioprostheses need a preprocessing to reduce noise and artifacts in order to enhance prosthetic leaflets. Stick based methods seems to provide an interesting approach for the morphological characterization of degenerated bioprostheses.RENNES1-Bibl. électronique (352382106) / SudocSudocFranceF