Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

Segmentation of brain MRI during early childhood

The objective of this thesis is the development of automatic methods to measure the changes in volume and growth of brain structures in prematurely born infants. Automatic tools for accurate tissue quantification from magnetic resonance images can provide means for understanding how the neurodevelopmental effects of the premature birth, such as cognitive, neurological or behavioural impairment, are related to underlying changes in brain anatomy. Understanding these changes forms a basis for development of suitable treatments to improve the outcomes of premature birth. In this thesis we focus on the segmentation of brain structures from magnetic resonance images during early childhood. Most of the current brain segmentation techniques have been focused on the segmentation of adult or neonatal brains. As a result of rapid development, the brain anatomy during early childhood differs from anatomy of both adult and neonatal brains and therefore requires adaptations of available techniques to produce good results. To address the issue of anatomical differences of the brain during early childhood compared to other age-groups, population-specific deformable and probabilistic atlases are introduced. A method for generation of population-specific prior information in form of a probabilistic atlas is proposed and used to enhance existing segmentation algorithms. The evaluation of registration-based and intensity-based approaches shows the techniques to be complementary in the quality of automatic segmentation in different parts of the brain. We propose a novel robust segmentation method combining the advantages of both approaches. The method is based on multiple label propagation using B-spline non-rigid registration followed by EM segmentation. Intensity inhomogeneity is a shading artefact resulting from the acquisition process, which significantly affects modern high resolution MR data acquired at higher magnetic field strengths. A novel template based method focused on correcting the intensity inhomogeneity in data acquired at higher magnetic field strengths is therefore proposed. The proposed segmentation method combined with proposed intensity inhomogeneity correction method offers a robust tool for quantification of volumes and growth of brain structures during early childhood. The tool have been applied to 67 T1-weigted images of subject at one and two years of age

Segmentation of image ensembles via latent atlases

Spatial priors, such as probabilistic atlases, play an important role in MRI segmentation. However, the availability of comprehensive, reliable and suitable manual segmentations for atlas construction is limited. We therefore propose a method for joint segmentation of corresponding regions of interest in a collection of aligned images that does not require labeled training data. Instead, a latent atlas, initialized by at most a single manual segmentation, is inferred from the evolving segmentations of the ensemble. The algorithm is based on probabilistic principles but is solved using partial differential equations (PDEs) and energy minimization criteria. We evaluate the method on two datasets, segmenting subcortical and cortical structures in a multi-subject study and extracting brain tumors in a single-subject multi-modal longitudinal experiment. We compare the segmentation results to manual segmentations, when those exist, and to the results of a state-of-the-art atlas-based segmentation method. The quality of the results supports the latent atlas as a promising alternative when existing atlases are not compatible with the images to be segmented.National Institutes of Health (U.S.) (National Institute for Biomedical Imaging and Bioengineering (U.S.)/National Alliance for Medical Image Computing (U.S.) U54-EB005149)National Institutes of Health (U.S.) (National Center for Research Resources (U.S.)/Neuroimaging Analysis Center (U.S.) P41-RR13218)National Institutes of Health (U.S.) (National Institute of Neurological Disorders and Stroke (U.S.) R01-NS051826)National Institutes of Health (U.S.) (National Center for Research Resources (U.S.)/Biomedical Informatics Research Network U24-RR021382)National Science Foundation (U.S.) (CAREER Award 0642971)German Academy of Sciences Leopoldina (Fellowship LPDS 2009-10)Academy of Finland (Grant 133611

Automated Extraction of Biomarkers for Alzheimer's Disease from Brain Magnetic Resonance Images

In this work, different techniques for the automated extraction of biomarkers for Alzheimer's disease (AD) from brain magnetic resonance imaging (MRI) are proposed. The described work forms part of PredictAD (www.predictad.eu), a joined European research project aiming at the identification of a unified biomarker for AD combining different clinical and imaging measurements. Two different approaches are followed in this thesis towards the extraction of MRI-based biomarkers: (I) the extraction of traditional morphological biomarkers based on neuronatomical structures and (II) the extraction of data-driven biomarkers applying machine-learning techniques. A novel method for a unified and automated estimation of structural volumes and volume changes is proposed. Furthermore, a new technique that allows the low-dimensional representation of a high-dimensional image population for data analysis and visualization is described. All presented methods are evaluated on images from the Alzheimer's Disease Neuroimaging Initiative (ADNI), providing a large and diverse clinical database. A rigorous evaluation of the power of all identified biomarkers to discriminate between clinical subject groups is presented. In addition, the agreement of automatically derived volumes with reference labels as well as the power of the proposed method to measure changes in a subject's atrophy rate are assessed. The proposed methods compare favorably to state-of-the art techniques in neuroimaging in terms of accuracy, robustness and run-time

Segmentation of pelvic structures from preoperative images for surgical planning and guidance

Prostate cancer is one of the most frequently diagnosed malignancies globally and the second leading cause of cancer-related mortality in males in the developed world. In recent decades, many techniques have been proposed for prostate cancer diagnosis and treatment. With the development of imaging technologies such as CT and MRI, image-guided procedures have become increasingly important as a means to improve clinical outcomes. Analysis of the preoperative images and construction of 3D models prior to treatment would help doctors to better localize and visualize the structures of interest, plan the procedure, diagnose disease and guide the surgery or therapy. This requires efficient and robust medical image analysis and segmentation technologies to be developed. The thesis mainly focuses on the development of segmentation techniques in pelvic MRI for image-guided robotic-assisted laparoscopic radical prostatectomy and external-beam radiation therapy. A fully automated multi-atlas framework is proposed for bony pelvis segmentation in MRI, using the guidance of MRI AE-SDM. With the guidance of the AE-SDM, a multi-atlas segmentation algorithm is used to delineate the bony pelvis in a new \ac{MRI} where there is no CT available. The proposed technique outperforms state-of-the-art algorithms for MRI bony pelvis segmentation. With the SDM of pelvis and its segmented surface, an accurate 3D pelvimetry system is designed and implemented to measure a comprehensive set of pelvic geometric parameters for the examination of the relationship between these parameters and the difficulty of robotic-assisted laparoscopic radical prostatectomy. This system can be used in both manual and automated manner with a user-friendly interface. A fully automated and robust multi-atlas based segmentation has also been developed to delineate the prostate in diagnostic MR scans, which have large variation in both intensity and shape of prostate. Two image analysis techniques are proposed, including patch-based label fusion with local appearance-specific atlases and multi-atlas propagation via a manifold graph on a database of both labeled and unlabeled images when limited labeled atlases are available. The proposed techniques can achieve more robust and accurate segmentation results than other multi-atlas based methods. The seminal vesicles are also an interesting structure for therapy planning, particularly for external-beam radiation therapy. As existing methods fail for the very onerous task of segmenting the seminal vesicles, a multi-atlas learning framework via random decision forests with graph cuts refinement has further been proposed to solve this difficult problem. Motivated by the performance of this technique, I further extend the multi-atlas learning to segment the prostate fully automatically using multispectral (T1 and T2-weighted) MR images via hybrid \ac{RF} classifiers and a multi-image graph cuts technique. The proposed method compares favorably to the previously proposed multi-atlas based prostate segmentation. The work in this thesis covers different techniques for pelvic image segmentation in MRI. These techniques have been continually developed and refined, and their application to different specific problems shows ever more promising results.Open Acces

Development of a tool for automatic segmentation of the cerebellum in MR images of children

The human cerebellar cortex is a highly foliated structure that supports both motor and complex cognitive functions in humans. Magnetic Resonance Imaging (MRI) is commonly used to explore structural alterations in patients with psychiatric and neurological diseases. The ability to detect regional structural differences in cerebellar lobules may provide valuable insights into disease biology, progression and response to treatment, but has been hampered by the lack of appropriate tools for performing automated structural cerebellar segmentation and morphometry. In this thesis, time intensive manual tracings by an expert neuroanatomist of 16 cerebellar regions on high-resolution T1-weighted MR images of 18 children aged 9-13 years were used to generate the Cape Town Pediatric Cerebellar Atlas (CAPCA18) in the age-appropriate National Institute of Health Pediatric Database (NIHPD) asymmetric template space. An automated pipeline was developed to process the MR images and generate lobule-wise segmentations, as well as a measure of the uncertainty of the label assignments. Validation in an independent group of children with ages similar to those of the children used in the construction of the atlas, yielded spatial overlaps with manual segmentations greater than 70% in all lobules, except lobules VIIb and X. Average spatial overlap of the whole cerebellar cortex was 86%, compared to 78% using the alternative Spatially Unbiased Infra-tentorial Template (SUIT), which was developed using adult images

Manual-protocol inspired technique for improving automated MR image segmentation during label fusion

Recent advances in multi-atlas based algorithms address many of the previous limitations in model-based and probabilistic segmentation methods. However, at the label fusion stage, a majority of algorithms focus primarily on optimizing weight-maps associated with the atlas library based on a theoretical objective function that approximates the segmentation error. In contrast, we propose a novel method-Autocorrecting Walks over Localized Markov Random Fields (AWoL-MRF)-that aims at mimicking the sequential process of manual segmentation, which is the gold-standard for virtually all the segmentation methods. AWoL-MRF begins with a set of candidate labels generated by a multi-atlas segmentation pipeline as an initial label distribution and refines low confidence regions based on a localized Markov random field (L-MRF) model using a novel sequential inference process (walks). We show that AWoL-MRF produces state-of-the-art results with superior accuracy and robustness with a small atlas library compared to existing methods. We validate the proposed approach by performing hippocampal segmentations on three independent datasets: (1) Alzheimer\u27s Disease Neuroimaging Database (ADNI); (2) First Episode Psychosis patient cohort; and (3) A cohort of preterm neonates scanned early in life and at term-equivalent age. We assess the improvement in the performance qualitatively as well as quantitatively by comparing AWoL-MRF with majority vote, STAPLE, and Joint Label Fusion methods. AWoL-MRF reaches a maximum accuracy of 0.881 (dataset 1), 0.897 (dataset 2), and 0.807 (dataset 3) based on Dice similarity coefficient metric, offering significant performance improvements with a smaller atlas library (\u3c 10) over compared methods. We also evaluate the diagnostic utility of AWoL-MRF by analyzing the volume differences per disease category in the ADNI1: Complete Screening dataset. We have made the source code for AWoL-MRF public at: https://github.com/CobraLab/AWoL-MRF

Master of Science

thesisMultisite imaging studies have the potential to accelerate scientific discovery by providing increased sample sizes, broader ranges of participant demographics, and publicly available data. However, failing to address the known nuisance variability across sites, such as scanner type or imaging protocol, reduces statistical power of any analysis performed on the multisite data. In this thesis, I present three contributions to the field of medical image analysis that are designed to reduce this known variability. These contributions include a feature reduction technique for pairwise correlation functional-magnetic resonance imaging (fMRI) data used as features in a multisite support vector machine (SVM), a subject-level network estimation technique for structural magnetic resonance imaging (MRI), and a hierarchical atlas estimation approach that accounts for intersite variability, while providing a global atlas as a common coordinate system for images across all sites. All results are presented on the Autism Brain Imaging Data Exchange (ABIDE) data set which contains resting-state fMRI (rs-fMRI) and structural MRI for 1112 subjects, including both autism and control groups. These methods result in state-of-the-art classification accuracy on the ABIDE data set and increased efficiency in reducing overall MRI data variability