A generative probability model of joint label fusion for multi-atlas based brain segmentation

Automated labeling of anatomical structures in medical images is very important in many neuroscience studies. Recently, patch-based labeling has been widely investigated to alleviate the possible mis-alignment when registering atlases to the target image. However, the weights used for label fusion from the registered atlases are generally computed independently and thus lack the capability of preventing the ambiguous atlas patches from contributing to the label fusion. More critically, these weights are often calculated based only on the simple patch similarity, thus not necessarily providing optimal solution for label fusion. To address these limitations, we propose a generative probability model to describe the procedure of label fusion in a multi-atlas scenario, for the goal of labeling each point in the target image by the best representative atlas patches that also have the largest labeling unanimity in labeling the underlying point correctly. Specifically, sparsity constraint is imposed upon label fusion weights, in order to select a small number of atlas patches that best represent the underlying target patch, thus reducing the risks of including the misleading atlas patches. The labeling unanimity among atlas patches is achieved by exploring their dependencies, where we model these dependencies as the joint probability of each pair of atlas patches in correctly predicting the labels, by analyzing the correlation of their morphological error patterns and also the labeling consensus among atlases. The patch dependencies will be further recursively updated based on the latest labeling results to correct the possible labeling errors, which falls to the Expectation Maximization (EM) framework. To demonstrate the labeling performance, we have comprehensively evaluated our patch-based labeling method on the whole brain parcellation and hippocampus segmentation. Promising labeling results have been achieved with comparison to the conventional patch-based labeling method, indicating the potential application of the proposed method in the future clinical studies

State of the Art of Level Set Methods in Segmentation and Registration of Medical Imaging Modalities

Segmentation of medical images is an important step in various applications such as visualization, quantitative analysis and image-guided surgery. Numerous segmentation methods have been developed in the past two decades for extraction of organ contours on medical images. Low-level segmentation methods, such as pixel-based clustering, region growing, and filter-based edge detection, require additional pre-processing and post-processing as well as considerable amounts of expert intervention or information of the objects of interest. Furthermore the subsequent analysis of segmented objects is hampered by the primitive, pixel or voxel level representations from those region-based segmentation. Deformable models, on the other hand, provide an explicit representation of the boundary and the shape of the object. They combine several desirable features such as inherent connectivity and smoothness, which counteract noise and boundary irregularities, as well as the ability to incorporate knowledge about the object of interest. However, parametric deformable models have two main limitations. First, in situations where the initial model and desired object boundary differ greatly in size and shape, the model must be re-parameterized dynamically to faithfully recover the object boundary. The second limitation is that it has difficulty dealing with topological adaptation such as splitting or merging model parts, a useful property for recovering either multiple objects or objects with unknown topology. This difficulty is caused by the fact that a new parameterization must be constructed whenever topology change occurs, which requires sophisticated schemes. Level set deformable models, also referred to as geometric deformable models, provide an elegant solution to address the primary limitations of parametric deformable models. These methods have drawn a great deal of attention since their introduction in 1988. Advantages of the contour implicit formulation of the deformable model over parametric formulation include: (1) no parameterization of the contour, (2) topological flexibility, (3) good numerical stability, (4) straightforward extension of the 2D formulation to n-D. Recent reviews on the subject include papers from Suri. In this chapter we give a general overview of the level set segmentation methods with emphasize on new frameworks recently introduced in the context of medical imaging problems. We then introduce novel approaches that aim at combining segmentation and registration in a level set formulation. Finally we review a selective set of clinical works with detailed validation of the level set methods for several clinical applications

Automated Morphometric Characterization of the Cerebral Cortex for the Developing and Ageing Brain

Morphometric characterisation of the cerebral cortex can provide information about patterns of brain development and ageing and may be relevant for diagnosis and estimation of the progression of diseases such as Alzheimer's, Huntington's, and schizophrenia. Therefore, understanding and describing the differences between populations in terms of structural volume, shape and thickness is of critical importance. Methodologically, due to data quality, presence of noise, PV effects, limited resolution and pathological variability, the automated, robust and time-consistent estimation of morphometric features is still an unsolved problem. This thesis focuses on the development of tools for robust cross-sectional and longitudinal morphometric characterisation of the human cerebral cortex. It describes techniques for tissue segmentation, structural and morphometric characterisation, cross-sectional and longitudinally cortical thickness estimation from serial MRI images in both adults and neonates. Two new probabilistic brain tissue segmentation techniques are introduced in order to accurately and robustly segment the brain of elderly and neonatal subjects, even in the presence of marked pathology. Two other algorithms based on the concept of multi-atlas segmentation propagation and fusion are also introduced in order to parcelate the brain into its multiple composing structures with the highest possible segmentation accuracy. Finally, we explore the use of the Khalimsky cubic complex framework for the extraction of topologically correct thickness measurements from probabilistic segmentations without explicit parametrisation of the edge. A longitudinal extension of this method is also proposed. The work presented in this thesis has been extensively validated on elderly and neonatal data from several scanners, sequences and protocols. The proposed algorithms have also been successfully applied to breast and heart MRI, neck and colon CT and also to small animal imaging. All the algorithms presented in this thesis are available as part of the open-source package NiftySeg

Analysis of the developing brain using image registration

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The anthropometric, environmental and genetic determinants of right ventricular structure and function

BACKGROUND Measures of right ventricular (RV) structure and function have significant prognostic value. The right ventricle is currently assessed by global measures, or point surrogates, which are insensitive to regional and directional changes. We aim to create a high-resolution three-dimensional RV model to improve understanding of its structural and functional determinants. These may be particularly of interest in pulmonary hypertension (PH), a condition in which RV function and outcome are strongly linked. PURPOSE To investigate the feasibility and additional benefit of applying three-dimensional phenotyping and contemporary statistical and genetic approaches to large patient populations. METHODS Healthy subjects and incident PH patients were prospectively recruited. Using a semi-automated atlas-based segmentation algorithm, 3D models characterising RV wall position and displacement were developed, validated and compared with anthropometric, physiological and genetic influences. Statistical techniques were adapted from other high-dimensional approaches to deal with the problems of multiple testing, contiguity, sparsity and computational burden. RESULTS 1527 healthy subjects successfully completed high-resolution 3D CMR and automated segmentation. Of these, 927 subjects underwent next-generation sequencing of the sarcomeric gene titin and 947 subjects completed genotyping of common variants for genome-wide association study. 405 incident PH patients were recruited, of whom 256 completed phenotyping. 3D modelling demonstrated significant reductions in sample size compared to two-dimensional approaches. 3D analysis demonstrated that RV basal-freewall function reflects global functional changes most accurately and that a similar region in PH patients provides stronger survival prediction than all anthropometric, haemodynamic and functional markers. Vascular stiffness, titin truncating variants and common variants may also contribute to changes in RV structure and function. CONCLUSIONS High-resolution phenotyping coupled with computational analysis methods can improve insights into the determinants of RV structure and function in both healthy subjects and PH patients. Large, population-based approaches offer physiological insights relevant to clinical care in selected patient groups.Open Acces

Combining spatial priors and anatomical information for fMRI detection

In this paper, we analyze Markov Random Field (MRF) as a spatial regularizer in fMRI detection. The low signal-to-noise ratio (SNR) in fMRI images presents a serious challenge for detection algorithms, making regularization necessary to achieve good detection accuracy. Gaussian smoothing, traditionally employed to boost SNR, often produces over-smoothed activation maps. Recently, the use of MRF priors has been suggested as an alternative regularization approach. However, solving for an optimal configuration of the MRF is NP-hard in general. In this work, we investigate fast inference algorithms based on the Mean Field approximation in application to MRF priors for fMRI detection. Furthermore, we propose a novel way to incorporate anatomical information into the MRF-based detection framework and into the traditional smoothing methods. Intuitively speaking, the anatomical evidence increases the likelihood of activation in the gray matter and improves spatial coherency of the resulting activation maps within each tissue type. Validation using the receiver operating characteristic (ROC) analysis and the confusion matrix analysis on simulated data illustrates substantial improvement in detection accuracy using the anatomically guided MRF spatial regularizer. We further demonstrate the potential benefits of the proposed method in real fMRI signals of reduced length. The anatomically guided MRF regularizer enables significant reduction of the scan length while maintaining the quality of the resulting activation maps.National Institutes of Health (U.S.) (National Institute for Biomedical Imaging and Bioengineering (U.S.)/National Alliance for Medical Image Computing (U.S.) Grant U54-EB005149)National Science Foundation (U.S.) (Grant IIS 9610249)National Institutes of Health (U.S.) (National Center for Research Resources (U.S.)/Biomedical Informatics Research Network Grant U24-RR021382)National Institutes of Health (U.S.) (National Center for Research Resources (U.S.)/Neuroimaging Analysis Center (U.S.) Grant P41-RR13218)National Institutes of Health (U.S.) (National Institute of Neurological Disorders and Stroke (U.S.) Grant R01-NS051826)National Science Foundation (U.S.) (CAREER Grant 0642971)National Science Foundation (U.S.). Graduate Research FellowshipNational Center for Research Resources (U.S.) (FIRST-BIRN Grant)Neuroimaging Analysis Center (U.S.

Machine Learning Methods for Depression Detection Using SMRI and RS-FMRI Images

Major Depression Disorder (MDD) is a common disease throughout the world that negatively influences people’s lives. Early diagnosis of MDD is beneficial, so detecting practical biomarkers would aid clinicians in the diagnosis of MDD. Having an automated method to find biomarkers for MDD is helpful even though it is difficult. The main aim of this research is to generate a method for detecting discriminative features for MDD diagnosis based on Magnetic Resonance Imaging (MRI) data. In this research, representational similarity analysis provides a framework to compare distributed patterns and obtain the similarity/dissimilarity of brain regions. Regions are obtained by either data-driven or model-driven methods such as cubes and atlases respectively. For structural MRI (sMRI) similarity of voxels of spatial cubes (data-driven) are explored. For resting-state fMRI (rs-fMRI) images, the similarity of the time series of both cubes (data-driven) and atlases (model-driven) are examined. Moreover, the similarity method of the inverse of Minimum Covariant Determinant is applied that excludes outliers from patterns and finds conditionally independent regions given the rest of regions. Next, a statistical test that is robust to outliers, identifies discriminative similarity features between two groups of MDDs and controls. Therefore, the key contribution is the way to get discriminative features that include obtaining similarity of voxel’s cubes/time series using the inverse of robust covariance along with the statistical test. The experimental results show that obtaining these features along with the Bernoulli Naïve Bayes classifier achieves superior performance compared with other methods. The performance of our method is verified by applying it to three imbalanced datasets. Moreover, the similarity-based methods are compared with deep learning and regional-based approaches for detecting MDD using either sMRI or rs-fMRI. Given that depression is famous to be a connectivity disorder problem, investigating the similarity of the brain’s regions is valuable to understand the behavior of the brain. The combinations of structural and functional brain similarities are explored to investigate the brain’s structural and functional properties together. Moreover, the combination of data-driven (cube) and model-driven (atlas) similarities of rs-fMRI are looked over to evaluate how they affect the performance of the classifier. Besides, discriminative similarities are visualized for both sMRI and rs-fMRI. Also, to measure the informativeness of a cube, the relationship of atlas regions with overlapping cubes and vise versa (cubes with overlapping regions) are explored and visualized. Furthermore, the relationship between brain structure and function has been probed through common similarities between structural and resting-state functional networks

Imaging mouse models of neurodegeneration using multi-parametric MRI

Alzheimer’s disease (AD) is a devastating condition characterised by significant cognitive impairment and memory loss. Transgenic mouse models are increasingly being used to further our knowledge of the cause and progression of AD, and identify new targets for therapeutic intervention. These mice permit the study of specific pathological hallmarks of the disease, including intracellular deposits of hyperphosphorylated tau protein and extracellular amyloid plaques. In order to characterise these transgenic mice, robust biomarkers are required to evaluate neurodegenerative changes and facilitate preclinical evaluation of emerging therapeutics. In this work, a platform for in vivo structural imaging of the rTg4510 mouse model of tauopathy was developed and optimised. This was combined with a range of other clinically relevant magnetic resonance imaging (MRI) biomarkers including: arterial spin labelling, diffusion tensor imaging and chemical exchange saturation transfer. These techniques were applied in a single time-point study of aged rTg4510 mice, as well as a longitudinal study to serially assess neurodegeneration in the same cohort of animals. Doxycycline was administered to a subset of rTg4510 mice to suppress the tau transgene; this novel intervention strategy permitted the evaluation of the sensitivity of MRI biomarkers to the accumulation and suppression of tau. Follow-up ex vivo scans were acquired in order to assess the sensitivity of in vivo structural MRI to the current preclinical gold standard. High resolution structural MRI, when used in conjunction with advanced computational analysis, yielded high sensitivity to pathological changes occurring in the rTg4510 mouse. Atrophy was reduced in animals treated with doxycycline. All other MRI biomarkers were able to discriminate between doxycycline-treated and untreated rTg4510 mice as well as wildtype controls, and provided insight into complimentary pathological mechanisms occurring within the disease process. In addition, this imaging protocol was applied to the J20 mouse model of familial AD. This mouse exhibits widespread plaque formation, enabling the study of amyloid-specific pathological changes. Atrophy and deficits in cerebral blood flow were observed; however, the changes occurring in this model were markedly less than those observed in the rTg4510 mouse. This study was expanded to investigate the early-onset AD observed in individuals with Down’s syndrome (DS) by breeding the J20 mouse with the Tc1 mouse model of DS, permitting the relationship between genetics and neurodegeneration to be dissected. This thesis demonstrates the application of in vivo multi-parametric MRI to mouse models of neurodegeneration. All techniques were sensitive to pathological changes occurring in the models, and may serve as important biomarkers in clinical studies of AD. In addition, in vivo multi-parametric MRI permits longitudinal studies of the same animal cohort. This experimental design produces more powerful results, whilst contributing to worldwide efforts to reduce animal usage with respect to the 3Rs principles