Elastic Registration of Biological Images Using Vector-Spline Regularization

We present an elastic registration algorithm for the alignment of biological images. Our method combines and extends some of the best techniques available in the context of medical imaging. We express the deformation field as a B-spline model, which allows us to deal with a rich variety of deformations. We solve the registration problem by minimizing a pixelwise mean-square distance measure between the target image and the warped source. The problem is further constrained by way of a vector-spline regularization which provides some control over two independent quantities that are intrinsic to the deformation: its divergence, and its curl. Our algorithm is also able to handle soft landmark constraints, which is particularly useful when parts of the images contain very little information or when its repartition is uneven. We provide an optimal analytical solution in the case when only landmarks and smoothness considerations are taken into account. We have applied our approach to perform the elastic registration of images such as electrophoretic gels and fly embryos. The validation of the results by experts has been favorable in all cases

Deformable Image Registration Using Convolutional Neural Networks for Connectomics

Department of Computer Science and EngineeringIn this thesis, a new novel method to align two images with recent deep learning scheme called ssEMnet is presented. The reconstruction of serial-section electron microscopy (ssEM) images gives critical insight to neuroscientist understanding real brains. However, alignment of each ssEM plane is not straightforward because of its densely twisted circuit structures. In addition, dynamic deformations are applied to images in the process of acquiring ssEM dataset from specimens. Even worse, non-matched artifacts like dusts and folds occur in the EM images. In recent deep learning researches, especially related with convolutional neural networks (CNNs) have shown to be able to handle various problems in computer vision area. However, there is no clear success on ssEM image registration problem using CNNs. ssEMnet is constructed with two parts. The first part is a spatial transformer module which supports differentiable transformation of images in deep neural network. A convolutional autoencoder (CAE) which encodes dense features follows. The CAE is trained by unsupervised fashion and its features give wide receptive field information to align the source and target images. This method is compared with two other major ssEM image registration methods and increases accuracy and robustness, although it has less number of user parameters.ope

Scalable Machine Learning Methods for Massive Biomedical Data Analysis.

Modern data acquisition techniques have enabled biomedical researchers to collect and analyze datasets of substantial size and complexity. The massive size of these datasets allows us to comprehensively study the biological system of interest at an unprecedented level of detail, which may lead to the discovery of clinically relevant biomarkers. Nonetheless, the dimensionality of these datasets presents critical computational and statistical challenges, as traditional statistical methods break down when the number of predictors dominates the number of observations, a setting frequently encountered in biomedical data analysis. This difficulty is compounded by the fact that biological data tend to be noisy and often possess complex correlation patterns among the predictors. The central goal of this dissertation is to develop a computationally tractable machine learning framework that allows us to extract scientifically meaningful information from these massive and highly complex biomedical datasets. We motivate the scope of our study by considering two important problems with clinical relevance: (1) uncertainty analysis for biomedical image registration, and (2) psychiatric disease prediction based on functional connectomes, which are high dimensional correlation maps generated from resting state functional MRI.PhDElectrical Engineering: SystemsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111354/1/takanori_1.pd

Assisting digital volume correlation with mechanical image-based modeling: application to the measurement of kinematic fields at the architecture scale in cellular materials

La mesure de champs de déplacement et de déformation aux petites échelles dans des microstructures complexes représente encore un défi majeur dans le monde de la mécanique expérimentale. Ceci est en partie dû aux acquisitions d'images et à la pauvreté de la texture à ces échelles. C'est notamment le cas pour les matériaux cellulaires lorsqu'ils sont imagés avec des micro-tomographes conventionnels et qu'ils peuvent être sujets à des mécanismes de déformation complexes. Comme la validation de modèles numériques et l'identification des propriétés mécaniques de matériaux se base sur des mesures précises de déplacements et de déformations, la conception et l'implémentation d'algorithmes robustes et fiables de corrélation d'images semble nécessaire. Lorsque l'on s'intéresse à l'utilisation de la corrélation d'images volumiques (DVC) pour les matériaux cellulaires, on est confronté à un paradoxe: l'absence de texture à l'échelle du constituant conduit à considérer l'architecture comme marqueur pour la corrélation. Ceci conduit à l'échec des techniques ordinaires de DVC à mesurer des cinématiques aux échelles subcellulaires en lien avec des comportements mécaniques locaux complexes tels que la flexion ou le flambement de travées. L'objectif de cette thèse est la conception d'une technique de DVC pour la mesure de champs de déplacement dans des matériaux cellulaires à l'échelle de leurs architectures. Cette technique assiste la corrélation d'images par une régularisation élastique faible en utilisant un modèle mécanique généré automatiquement et basé sur les images. La méthode suggérée introduit une séparation d'échelles au dessus desquelles la DVC est dominante et en dessous desquelles elle est assistée par le modèle mécanique basé sur l'image. Une première étude numérique consistant à comparer différentes techniques de construction de modèles mécaniques basés sur les images est conduite. L'accent est mis sur deux méthodes de calcul particulières: la méthode des éléments finis (FEM) et la méthode des cellules finies (FCM) qui consiste à immerger la géométrie complexe dans une grille régulière de haut ordre sans utiliser de mailleurs. Si la FCM évite une première phase délicate de discrétisation, plusieurs paramètres restent néanmoins délicats à fixer. Dans ce travail, ces paramètres sont ajustés afin d'obtenir (a) la meilleure précision (bornée par les erreurs de pixellisation) tout en (b) assurant une complexité minimale. Pour l'aspect mesure par corrélation d'images régularisée, plusieurs expérimentations virtuelles à partir de différentes simulations numériques (en élasticité, en plasticité et en non-linéarité géométrique) sont d'abord réalisées afin d'analyser l'influence des paramètres de régularisation introduits. Les erreurs de mesures peuvent dans ce cas être quantifiées à l'aide des solutions de référence éléments finis. La capacité de la méthode à mesurer des cinématiques complexes en absence de texture est démontrée pour des régimes non-linéaires tels que le flambement. Finalement, le travail proposé est généralisé à la corrélation volumique des différents états de déformation du matériau et à la construction automatique de la micro-architecture cellulaire en utilisant soit une grille B-spline d'ordre arbitraire (FCM) soit un maillage éléments finis (FEM). Une mise en évidence expérimentale de l'efficacité et de la justesse de l'approche proposée est effectuée à travers de la mesure de cinématiques complexes dans une mousse polyuréthane sollicitée en compression lors d'un essai in situ.Measuring displacement and strain fields at low observable scales in complex microstructures still remains a challenge in experimental mechanics often because of the combination of low definition images with poor texture at this scale. The problem is particularly acute in the case of cellular materials, when imaged by conventional micro-tomographs, for which complex highly non-linear local phenomena can occur. As the validation of numerical models and the identification of mechanical properties of materials must rely on accurate measurements of displacement and strain fields, the design and implementation of robust and faithful image correlation algorithms must be conducted. With cellular materials, the use of digital volume correlation (DVC) faces a paradox: in the absence of markings of exploitable texture on/or in the struts or cell walls, the available speckle will be formed by the material architecture itself. This leads to the inability of classical DVC codes to measure kinematics at the cellular and a fortiori sub-cellular scales, precisely because the interpolation basis of the displacement field cannot account for the complexity of the underlying kinematics, especially when bending or buckling of beams or walls occurs. The objective of the thesis is to develop a DVC technique for the measurement of displacement fields in cellular materials at the scale of their architecture. The proposed solution consists in assisting DVC by a weak elastic regularization using an automatic image-based mechanical model. The proposed method introduces a separation of scales above which DVC is dominant and below which it is assisted by image-based modeling. First, a numerical investigation and comparison of different techniques for building automatically a geometric and mechanical model from tomographic images is conducted. Two particular methods are considered: the finite element method (FEM) and the finite-cell method (FCM). The FCM is a fictitious domain method that consists in immersing the complex geometry in a high order structured grid and does not require meshing. In this context, various discretization parameters appear delicate to choose. In this work, these parameters are adjusted to obtain (a) the best possible accuracy (bounded by pixelation errors) while (b) ensuring minimal complexity. Concerning the ability of the mechanical image-based models to regularize DIC, several virtual experimentations are performed in two-dimensions in order to finely analyze the influence of the introduced regularization lengths for different input mechanical behaviors (elastic, elasto-plastic and geometrically non-linear) and in comparison with ground truth. We show that the method can estimate complex local displacement and strain fields with speckle-free low definition images, even in non-linear regimes such as local buckling. Finally a three-dimensional generalization is performed through the development of a DVC framework. It takes as an input the reconstructed volumes at the different deformation states of the material and constructs automatically the cellular micro-architeture geometry. It considers either an immersed structured B-spline grid of arbitrary order or a finite-element mesh. An experimental evidence is performed by measuring the complex kinematics of a polyurethane foam under compression during an in situ test

3-D lung deformation and function from respiratory-gated 4-D x-ray CT images : application to radiation treatment planning.

Many lung diseases or injuries can cause biomechanical or material property changes that can alter lung function. While the mechanical changes associated with the change of the material properties originate at a regional level, they remain largely asymptomatic and are invisible to global measures of lung function until they have advanced significantly and have aggregated. In the realm of external beam radiation therapy of patients suffering from lung cancer, determination of patterns of pre- and post-treatment motion, and measures of regional and global lung elasticity and function are clinically relevant. In this dissertation, we demonstrate that 4-D CT derived ventilation images, including mechanical strain, provide an accurate and physiologically relevant assessment of regional pulmonary function which may be incorporated into the treatment planning process. Our contributions are as follows: (i) A new volumetric deformable image registration technique based on 3-D optical flow (MOFID) has been designed and implemented which permits the possibility of enforcing physical constraints on the numerical solutions for computing motion field from respiratory-gated 4-D CT thoracic images. The proposed optical flow framework is an accurate motion model for the thoracic CT registration problem. (ii) A large displacement landmark-base elastic registration method has been devised for thoracic CT volumetric image sets containing large deformations or changes, as encountered for example in registration of pre-treatment and post-treatment images or multi-modality registration. (iii) Based on deformation maps from MOFIO, a novel framework for regional quantification of mechanical strain as an index of lung functionality has been formulated for measurement of regional pulmonary function. (iv) In a cohort consisting of seven patients with non-small cell lung cancer, validation of physiologic accuracy of the 4-0 CT derived quantitative images including Jacobian metric of ventilation, Vjac, and principal strains, (V?1, V?2, V?3, has been performed through correlation of the derived measures with SPECT ventilation and perfusion scans. The statistical correlations with SPECT have shown that the maximum principal strain pulmonary function map derived from MOFIO, outperforms all previously established ventilation metrics from 40-CT. It is hypothesized that use of CT -derived ventilation images in the treatment planning process will help predict and prevent pulmonary toxicity due to radiation treatment. It is also hypothesized that measures of regional and global lung elasticity and function obtained during the course of treatment may be used to adapt radiation treatment. Having objective methods with which to assess pre-treatment global and regional lung function and biomechanical properties, the radiation treatment dose can potentially be escalated to improve tumor response and local control

Atlas Toolkit: Fast registration of 3D morphological datasets in the absence of landmarks

Image registration is a gateway technology for Developmental Systems Biology, enabling computational analysis of related datasets within a shared coordinate system. Many registration tools rely on landmarks to ensure that datasets are correctly aligned; yet suitable landmarks are not present in many datasets. Atlas Toolkit is a Fiji/ImageJ plugin collection offering elastic group-wise registration of 3D morphological datasets, guided by segmentation of the interesting morphology. We demonstrate the method by combinatorial mapping of cell signalling events in the developing eyes of chick embryos, and use the integrated datasets to predictively enumerate Gene Regulatory Network states