Motion robust acquisition and reconstruction of quantitative T2* maps in the developing brain

The goal of the research presented in this thesis was to develop methods for quantitative T2* mapping of the developing brain. Brain maturation in the early period of life involves complex structural and physiological changes caused by synaptogenesis, myelination and growth of cells. Molecular structures and biological processes give rise to varying levels of T2* relaxation time, which is an inherent contrast mechanism in magnetic resonance imaging. The knowledge of T2* relaxation times in the brain can thus help with evaluation of pathology by establishing its normative values in the key areas of the brain. T2* relaxation values are a valuable biomarker for myelin microstructure and iron concentration, as well as an important guide towards achievement of optimal fMRI contrast. However, fetal MR imaging is a significant step up from neonatal or adult MR imaging due to the complexity of the acquisition and reconstruction techniques that are required to provide high quality artifact-free images in the presence of maternal respiration and unpredictable fetal motion. The first contribution of this thesis, described in Chapter 4, presents a novel acquisition method for measurement of fetal brain T2* values. At the time of publication, this was the first study of fetal brain T2* values. Single shot multi-echo gradient echo EPI was proposed as a rapid method for measuring fetal T2* values by effectively freezing intra-slice motion. The study concluded that fetal T2* values are higher than those previously reported for pre-term neonates and decline with a consistent trend across gestational age. The data also suggested that longer than usual echo times or direct T2* measurement should be considered when performing fetal fMRI in order to reach optimal BOLD sensitivity. For the second contribution, described in Chapter 5, measurements were extended to a higher field strength of 3T and reported, for the first time, both for fetal and neonatal subjects at this field strength. The technical contribution of this work is a fully automatic segmentation framework that propagates brain tissue labels onto the acquired T2* maps without the need for manual intervention. The third contribution, described in Chapter 6, proposed a new method for performing 3D fetal brain reconstruction where the available data is sparse and is therefore limited in the use of current state of the art techniques for 3D brain reconstruction in the presence of motion. To enable a high resolution reconstruction, a generative adversarial network was trained to perform image to image translation between T2 weighted and T2* weighted data. Translated images could then be served as a prior for slice alignment and super resolution reconstruction of 3D brain image.Open Acces

Review : Deep learning in electron microscopy

Deep learning is transforming most areas of science and technology, including electron microscopy. This review paper offers a practical perspective aimed at developers with limited familiarity. For context, we review popular applications of deep learning in electron microscopy. Following, we discuss hardware and software needed to get started with deep learning and interface with electron microscopes. We then review neural network components, popular architectures, and their optimization. Finally, we discuss future directions of deep learning in electron microscopy

Compressed sensing and finite rate of innovation for efficient data acquisition of quantitative acoustic microscopy images

La microscopie acoustique quantitative (MAQ) est une modalité d'imagerie bien établie qui donne accès à des cartes paramétriques 2D représentatives des propriétés mécaniques des tissus à une échelle microscopique. Dans la plupart des études sur MAQ, l'échantillons est scanné ligne par ligne (avec un pas de 2µm) à l'aide d'un transducteur à 250 MHz. Ce type d'acquisition permet d'obtenir un cube de données RF 3D, avec deux dimensions spatiales et une dimension temporelle. Chaque signal RF correspondant à une position spatiale dans l'échantillon permet d'estimer des paramètres acoustiques comme par exemple la vitesse du son ou l'impédance. Le temps d'acquisition en MAQ est directement proportionnel à la taille de l'échantillon et peut aller de quelques minutes à quelques dizaines de minutes. Afin d'assurer des conditions d'acquisition stables et étant donnée la sensibilité des échantillons à ces conditions, diminuer le temps d'acquisition est un des grand défis en MAQ. Afin de relever ce défi, ce travail de thèse propose plusieurs solutions basées sur l'échantillonnage compressé (EC) et la théories des signaux ayant un faible nombre de degré de liberté (finite rate of innovation - FRI, en anglais). Le principe de l'EC repose sur la parcimonie des données, sur l'échantillonnage incohérent de celles-ci et sur les algorithmes d'optimisation numérique. Dans cette thèse, les phénomènes physiques derrière la MAQ sont exploités afin de créer des modèles adaptés aux contraintes de l'EC et de la FRI. Plus particulièrement, ce travail propose plusieurs pistes d'application de l'EC en MAQ : un schéma d'acquisition spatiale innovant, un algorithme de reconstruction d'images exploitant les statistiques des coefficients en ondelettes des images paramétriques, un modèle FRI adapté aux signaux RF et un schéma d'acquisition compressée dans le domaine temporel.Quantitative acoustic microscopy (QAM) is a well-accepted modality for forming 2D parameter maps making use of mechanical properties of soft tissues at microscopic scales. In leading edge QAM studies, the sample is raster-scanned (spatial step size of 2µm) using a 250 MHz transducer resulting in a 3D RF data cube, and each RF signal for each spatial location is processed to obtain acoustic parameters, e.g., speed of sound or acoustic impedance. The scanning time directly depends on the sample size and can range from few minutes to tens of minutes. In order to maintain constant experimental conditions for the sensitive thin sectioned samples, the scanning time is an important practical issue. To deal with the current challenge, we propose the novel approach inspired by compressed sensing (CS) and finite rate of innovation (FRI). The success of CS relies on the sparsity of data under consideration, incoherent measurement and optimization technique. On the other hand, the idea behind FRI is supported by a signal model fully characterized as a limited number of parameters. From this perspective, taking into account the physics leading to data acquisition of QAM system, the QAM data can be regarded as an adequate application amenable to the state of the art technologies aforementioned. However, when it comes to the mechanical structure of QAM system which does not support canonical CS measurement manners on the one hand, and the compositions of the RF signal model unsuitable to existing FRI schemes on the other hand, the advanced frameworks are still not perfect methods to resolve the problems that we are facing. In this thesis, to overcome the limitations, a novel sensing framework for CS is presented in spatial domain: a recently proposed approximate message passing (AMP) algorithm is adapted to account for the underlying data statistics of samples sparsely collected by proposed scanning patterns. In time domain, as an approach for achieving an accurate recovery from a small set of samples of QAM RF signals, we employ sum of sincs (SoS) sampling kernel and autoregressive (AR) model estimator. The spiral scanning manner, introduced as an applicable sensing technique to QAM system, contributed to the significant reduction of the number of spatial samples when reconstructing speed of sound images of a human lymph node. Furthermore, the scanning time was also hugely saved due to the merit of the mechanical movement of the proposed sensing pattern. Together with the achievement in spatial domain, the introduction of SoS kernel and AR estimator responsible for an innovation rate sampling and a parameter estimation respectively led to dramatic reduction of the required number of samples per RF signal compared to a conventional approach. Finally, we showed that both data acquisition frameworks based on the CS and FRI can be combined into a single spatio-temporal solution to maximize the benefits stated above

Restauration d'images en IRM anatomique pour l'étude préclinique des marqueurs du vieillissement cérébral

Les maladies neurovasculaires et neurodégénératives liées à l'âge sont en forte augmentation. Alors que ces changements pathologiques montrent des effets sur le cerveau avant l'apparition de symptômes cliniques, une meilleure compréhension du processus de vieillissement normal du cerveau aidera à distinguer l'impact des pathologies connues sur la structure régionale du cerveau. En outre, la connaissance des schémas de rétrécissement du cerveau dans le vieillissement normal pourrait conduire à une meilleure compréhension de ses causes et peut-être à des interventions réduisant la perte de fonctions cérébrales associée à l'atrophie cérébrale. Par conséquent, ce projet de thèse vise à détecter les biomarqueurs du vieillissement normal et pathologique du cerveau dans un modèle de primate non humain, le singe marmouset (Callithrix Jacchus), qui possède des caractéristiques anatomiques plus proches de celles des humains que de celles des rongeurs. Cependant, les changements structurels (par exemple, de volumes, d'épaisseur corticale) qui peuvent se produire au cours de leur vie adulte peuvent être minimes à l'échelle de l'observation. Dans ce contexte, il est essentiel de disposer de techniques d'observation offrant un contraste et une résolution spatiale suffisamment élevés et permettant des évaluations détaillées des changements morphométriques du cerveau associé au vieillissement. Cependant, l'imagerie de petits cerveaux dans une plateforme IRM 3T dédiée à l'homme est une tâche difficile car la résolution spatiale et le contraste obtenus sont insuffisants par rapport à la taille des structures anatomiques observées et à l'échelle des modifications attendues. Cette thèse vise à développer des méthodes de restauration d'image pour les images IRM précliniques qui amélioreront la robustesse des algorithmes de segmentation. L'amélioration de la résolution spatiale des images à un rapport signal/bruit constant limitera les effets de volume partiel dans les voxels situés à la frontière entre deux structures et permettra une meilleure segmentation tout en augmentant la reproductibilité des résultats. Cette étape d'imagerie computationnelle est cruciale pour une analyse morphométrique longitudinale fiable basée sur les voxels et l'identification de marqueurs anatomiques du vieillissement cérébral en suivant les changements de volume dans la matière grise, la matière blanche et le liquide cérébral.Age-related neurovascular and neurodegenerative diseases are increasing significantly. While such pathological changes show effects on the brain before clinical symptoms appear, a better understanding of the normal aging brain process will help distinguish known pathologies' impact on regional brain structure. Furthermore, knowledge of the patterns of brain shrinkage in normal aging could lead to a better understanding of its causes and perhaps to interventions reducing the loss of brain functions. Therefore, this thesis project aims to detect normal and pathological brain aging biomarkers in a non-human primate model, the marmoset monkey (Callithrix Jacchus) which possesses anatomical characteristics more similar to humans than rodents. However, structural changes (e.g., volumes, cortical thickness) that may occur during their adult life may be minimal with respect to the scale of observation. In this context, it is essential to have observation techniques that offer sufficiently high contrast and spatial resolution and allow detailed assessments of the morphometric brain changes associated with aging. However, imaging small brains in a 3T MRI platform dedicated to humans is a challenging task because the spatial resolution and the contrast obtained are insufficient compared to the size of the anatomical structures observed and the scale of the xpected changes with age. This thesis aims to develop image restoration methods for preclinical MR images that will improve the robustness of the segmentation algorithms. Improving the resolution of the images at a constant signal-to-noise ratio will limit the effects of partial volume in voxels located at the border between two structures and allow a better segmentation while increasing the results' reproducibility. This computational imaging step is crucial for a reliable longitudinal voxel-based morphometric analysis and for the identification of anatomical markers of brain aging by following the volume changes in gray matter, white matter and cerebrospinal fluid

Molecular Imaging

The present book gives an exceptional overview of molecular imaging. Practical approach represents the red thread through the whole book, covering at the same time detailed background information that goes very deep into molecular as well as cellular level. Ideas how molecular imaging will develop in the near future present a special delicacy. This should be of special interest as the contributors are members of leading research groups from all over the world

Optical Methods in Sensing and Imaging for Medical and Biological Applications

The recent advances in optical sources and detectors have opened up new opportunities for sensing and imaging techniques which can be successfully used in biomedical and healthcare applications. This book, entitled ‘Optical Methods in Sensing and Imaging for Medical and Biological Applications’, focuses on various aspects of the research and development related to these areas. The book will be a valuable source of information presenting the recent advances in optical methods and novel techniques, as well as their applications in the fields of biomedicine and healthcare, to anyone interested in this subject

Deep Learning for Detection and Segmentation in High-Content Microscopy Images

High-content microscopy led to many advances in biology and medicine. This fast emerging technology is transforming cell biology into a big data driven science. Computer vision methods are used to automate the analysis of microscopy image data. In recent years, deep learning became popular and had major success in computer vision. Most of the available methods are developed to process natural images. Compared to natural images, microscopy images pose domain specific challenges such as small training datasets, clustered objects, and class imbalance. In this thesis, new deep learning methods for object detection and cell segmentation in microscopy images are introduced. For particle detection in fluorescence microscopy images, a deep learning method based on a domain-adapted Deconvolution Network is presented. In addition, a method for mitotic cell detection in heterogeneous histopathology images is proposed, which combines a deep residual network with Hough voting. The method is used for grading of whole-slide histology images of breast carcinoma. Moreover, a method for both particle detection and cell detection based on object centroids is introduced, which is trainable end-to-end. It comprises a novel Centroid Proposal Network, a layer for ensembling detection hypotheses over image scales and anchors, an anchor regularization scheme which favours prior anchors over regressed locations, and an improved algorithm for Non-Maximum Suppression. Furthermore, a novel loss function based on Normalized Mutual Information is proposed which can cope with strong class imbalance and is derived within a Bayesian framework. For cell segmentation, a deep neural network with increased receptive field to capture rich semantic information is introduced. Moreover, a deep neural network which combines both paradigms of multi-scale feature aggregation of Convolutional Neural Networks and iterative refinement of Recurrent Neural Networks is proposed. To increase the robustness of the training and improve segmentation, a novel focal loss function is presented. In addition, a framework for black-box hyperparameter optimization for biomedical image analysis pipelines is proposed. The framework has a modular architecture that separates hyperparameter sampling and hyperparameter optimization. A visualization of the loss function based on infimum projections is suggested to obtain further insights into the optimization problem. Also, a transfer learning approach is presented, which uses only one color channel for pre-training and performs fine-tuning on more color channels. Furthermore, an approach for unsupervised domain adaptation for histopathological slides is presented. Finally, Galaxy Image Analysis is presented, a platform for web-based microscopy image analysis. Galaxy Image Analysis workflows for cell segmentation in cell cultures, particle detection in mice brain tissue, and MALDI/H&E image registration have been developed. The proposed methods were applied to challenging synthetic as well as real microscopy image data from various microscopy modalities. It turned out that the proposed methods yield state-of-the-art or improved results. The methods were benchmarked in international image analysis challenges and used in various cooperation projects with biomedical researchers