REGISTRATION AND SEGMENTATION OF BRAIN MR IMAGES FROM ELDERLY INDIVIDUALS

Quantitative analysis of the MRI structural and functional images is a fundamental component in the assessment of brain anatomical abnormalities, in mapping functional activation onto human anatomy, in longitudinal evaluation of disease progression, and in computer-assisted neurosurgery or surgical planning. Image registration and segmentation is central in analyzing structural and functional MR brain images. However, due to increased variability in brain morphology and age-related atrophy, traditional methods for image registration and segmentation are not suitable for analyzing MR brain images from elderly individuals. The overall goal of this dissertation is to develop algorithms to improve the registration and segmentation accuracy in the geriatric population. The specific aims of this work includes 1) to implement a fully deformable registration pipeline to allow a higher degree of spatial deformation and produce more accurate deformation field, 2) to propose and validate an optimum template selection method for atlas-based segmentation, 3) to propose and validate a multi-template strategy for image normalization, which characterizes brain structural variations in the elderly, 4) to develop an automated segmentation and localization method to access white matter integrity (WMH) in the elderly population, and finally 5) to study the default-mode network (DMN) connectivity and white matter hyperintensity in late-life depression (LLD) with the developed registration and segmentation methods. Through a series of experiments, we have shown that the deformable registration pipeline and the template selection strategies lead to improved accuracy in the brain MR image registration and segmentation, and the automated WMH segmentation and localization method provides more specific and more accurate information about volume and spatial distribution of WMH than traditional visual grading methods. Using the developed methods, our clinical study provides evidence for altered DMN connectivity in LLD. The correlation between WMH volume and DMN connectivity emphasizes the role of vascular changes in LLD's etiopathogenesis

Processing of diffusion MR images of the brain: from crossing fibres to distributed tractography

Diffusion-weighted (DW) magnetic resonance imaging allows the quantification of water diffusion within tissue. Due to the hindrance of water molecules by the various tissue compartments, probing for the diffusive properties of a region can provide information on the underlying structure. This is particularly useful for the human brain, whose anatomy is complex. Diffusion imaging provides currently the only tool to study the brain connectivity and organization non-invasively and in-vivo, through a group of methods, commonly referred to as tractography methods. This thesis is concerned with brain anatomical connectivity and tractography. The goal is to elucidate problems with existing approaches used to process DW images and propose solutions and methods through new frameworks. These concern data from two popular DW imaging protocols, diffusion tensor imaging (DTI) and high angular resolution diffusion imaging (HARDI), or Q-ball imaging in particular. One of the problems tackled is resolving crossing fibre configurations, a major concern in DW imaging, using data that can be routinely acquired in a clinical setting. The physical constraint of spatial continuity of the diffusion environment is imposed throughout the brain volume, using a multi-tensor model and a regularization method. The new approach is shown to improve tractography results through crossing regions. Quantitative tractography algorithms are also proposed that, apart from reconstructing the white matter tracts, assign relative indices of anatomical connectivity to all regions. A fuzzy algorithm is presented for assessing orientational coherence of neuronal tracts, reflecting the fuzzy nature of medical images. As shown for different tracts, where a-priori anatomical knowledge exists, regions that are coherently connected and possibly belong to the same tract can be differentiated from the background. In a different framework, elements of graph theory are used to develop a new tractography algorithm that can utilize information from multiple image modalities to assess brain connectivity. Both algorithms inherently consider crossing fibre information and are shown to solve problems that affect existing methods

Recommendations to improve imaging and analysis of brain lesion load and atrophy in longitudinal studies of multiple sclerosis

Focal lesions and brain atrophy are the most extensively studied aspects of multiple sclerosis (MS), but the image acquisition and analysis techniques used can be further improved, especially those for studying within-patient changes of lesion load and atrophy longitudinally. Improved accuracy and sensitivity will reduce the numbers of patients required to detect a given treatment effect in a trial, and ultimately, will allow reliable characterization of individual patients for personalized treatment. Based on open issues in the field of MS research, and the current state of the art in magnetic resonance image analysis methods for assessing brain lesion load and atrophy, this paper makes recommendations to improve these measures for longitudinal studies of MS. Briefly, they are (1) images should be acquired using 3D pulse sequences, with near-isotropic spatial resolution and multiple image contrasts to allow more comprehensive analyses of lesion load and atrophy, across timepoints. Image artifacts need special attention given their effects on image analysis results. (2) Automated image segmentation methods integrating the assessment of lesion load and atrophy are desirable. (3) A standard dataset with benchmark results should be set up to facilitate development, calibration, and objective evaluation of image analysis methods for MS

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

Assessment and optimisation of MRI measures of atrophy as potential markers of disease progression in multiple sclerosis

There is a need for sensitive measures of disease progression in multiple sclerosis (MS) to monitor treatment effects and understand disease evolution. MRI measures of brain atrophy have been proposed for this purpose. This thesis investigates a number of measurement techniques to assess their relative ability to monitor disease progression in clinically isolated syndromes (CIS) and early relapsing remitting MS (RRMS). Presented, is work demonstrating that measurement techniques and MR acquisitions can be optimised to give small but significant improvements in measurement sensitivity and precision, which provided greater statistical power. Direct comparison of numerous techniques demonstrated significant differences between them. Atrophy measurements from SIENA and the BBSI (registration-based techniques) were significantly more precise than segmentation and subtraction of brain volumes, although larger percentage losses were observed in grey matter fraction. Ventricular enlargement (VE) gave similar statistical power and these techniques were robust and reliable; scan-rescan measurement error was <0.01% of brain volume for BBSI and SIENA and <0.04ml for VE. Annual atrophy rates (using SIENA) were -0.78% in RRMS and -0.52% in CIS patients who progressed to MS, which were significantly greater than the rate observed in controls (-0.07%). Sample size calculations for future trials of disease-modifying treatments in RRMS, using brain atrophy as an outcome measure, are described. For SIENA, the BBSI and VE respectively, an estimated 123, 157 and 140 patients per treatment arm respectively would be required to show a 30% slowing of atrophy rate over two years. In CIS subjects brain atrophy rate was a significant prognostic factor, independent of T2 MRI lesions at baseline, for development of MS by five year follow-up. It was also the most significant MR predictor of disability in RRMS subjects. Cognitive assessment of RRMS patients at five year follow-up is described, and brain atrophy rate was a significant predictor of overall cognitive performance, and more specifically, of performance in tests of memory. The work in this thesis has identified methods for sensitively measuring progressive brain atrophy in MS. It has shown that brain atrophy changes in early MS are related to early clinical evolution, providing complementary information to clinical assessment that could be utilised to monitor disease progression

A review of image processing methods for fetal head and brain analysis in ultrasound images

Background and objective: Examination of head shape and brain during the fetal period is paramount to evaluate head growth, predict neurodevelopment, and to diagnose fetal abnormalities. Prenatal ultrasound is the most used imaging modality to perform this evaluation. However, manual interpretation of these images is challenging and thus, image processing methods to aid this task have been proposed in the literature. This article aims to present a review of these state-of-the-art methods. Methods: In this work, it is intended to analyze and categorize the different image processing methods to evaluate fetal head and brain in ultrasound imaging. For that, a total of 109 articles published since 2010 were analyzed. Different applications are covered in this review, namely analysis of head shape and inner structures of the brain, standard clinical planes identification, fetal development analysis, and methods for image processing enhancement. Results: For each application, the reviewed techniques are categorized according to their theoretical approach, and the more suitable image processing methods to accurately analyze the head and brain are identified. Furthermore, future research needs are discussed. Finally, topics whose research is lacking in the literature are outlined, along with new fields of applications. Conclusions: A multitude of image processing methods has been proposed for fetal head and brain analysis. Summarily, techniques from different categories showed their potential to improve clinical practice. Nevertheless, further research must be conducted to potentiate the current methods, especially for 3D imaging analysis and acquisition and for abnormality detection. (c) 2022 Elsevier B.V. All rights reserved.FCT - Fundação para a Ciência e a Tecnologia(UIDB/00319/2020)This work was funded by projects “NORTE-01–0145-FEDER- 0 0 0 059 , NORTE-01-0145-FEDER-024300 and “NORTE-01–0145- FEDER-0 0 0 045 , supported by Northern Portugal Regional Opera- tional Programme (Norte2020), under the Portugal 2020 Partner- ship Agreement, through the European Regional Development Fund (FEDER). It was also funded by national funds, through the FCT – Fundação para a Ciência e Tecnologia within the R&D Units Project Scope: UIDB/00319/2020 and by FCT and FCT/MCTES in the scope of the projects UIDB/05549/2020 and UIDP/05549/2020 . The authors also acknowledge support from FCT and the Euro- pean Social Found, through Programa Operacional Capital Humano (POCH), in the scope of the PhD grant SFRH/BD/136670/2018 and SFRH/BD/136721/2018