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

Chip Based Optical Nanoscopy: System Integration and Automation

An integrated photonic chip based nanoscopy system has previously been developed at UiT, which allows for several advantages over conventional total internal reflection fluorescence microscopy and nanoscopy (i.e. super-resolutionnanoscopy). While the proof-of-concept has been demonstrated, there were several important system optimization tasks that were needed for making the system practical and more usable. This thesis tackles three major system optimization tasks, namely efficient and automatic coupling of light into waveguide in the photonic chip, precise control and stablization of feed point into the waveguide, and synchronization of illumination and collection arms of the photonic chip based microscope. For a novel and more flexible light feed setup designed at the department, a new mechanism for measuring the coupling efficiency was designed, an initial coupling and parasitic interaxis cross-talk compensation mechanism was designed, and two optimiztion algorithms were explored for the final fine coupling. Testing of the implementation showed promising results with close to optimal coupling efficiency achieved in a reasonable amount of time. A piezoelectric stage with large travel range was tuned to provide the best possible performance for controlling illumination. This was used to adapt a nanoscopy algorithm named multiple signal classification algorithm (MUSICAL) for exploiting the variable illumination property of multimode waveguides on the photonic chip. Lastly, imaging and illumination control was inplemented in software allowing the capture of datasets suitable for use with MUSICAL. Thus, the goals of this thesis were achieved successfully and the practical use ofthe photonic-chip for microscopy and nanoscopy was greatly enhanced

Symmetric diffeomorphic modeling of longtudinal structural MRI

This technology report describes the longitudinal registration approach that we intend to incorporate into SPM12. It essentially describes a group-wise intra-subject modeling framework, which combines diffeomorphic and rigid-body registration, incorporating a correction for the intensity inhomogeneity artifact usually seen in MRI data. Emphasis is placed on achieving internal consistency and accounting for many of the mathematical subtleties that most implementations overlook. The implementation was evaluated using examples from the OASIS Longitudinal MRI Data in Non-demented and Demented Older Adults

Fast and Robust Automatic Segmentation Methods for MR Images of Injured and Cancerous Tissues

Magnetic Resonance Imaging: MRI) is a key medical imaging technology. Through in vivo soft tissue imaging, MRI allows clinicians and researchers to make diagnoses and evaluations that were previously possible only through biopsy or autopsy. However, analysis of MR images by domain experts can be time-consuming, complex, and subject to bias. The development of automatic segmentation techniques that make use of robust statistical methods allows for fast and unbiased analysis of MR images. In this dissertation, I propose segmentation methods that fall into two classes---(a) segmentation via optimization of a parametric boundary, and: b) segmentation via multistep, spatially constrained intensity classification. These two approaches are applicable in different segmentation scenarios. Parametric boundary segmentation is useful and necessary for segmentation of noisy images where the tissue of interest has predictable shape but poor boundary delineation, as in the case of lung with heavy or diffuse tumor. Spatially constrained intensity classification is appropriate for segmentation of noisy images with moderate contrast between tissue regions, where the areas of interest have unpredictable shapes, as is the case in spinal injury and brain tumor. The proposed automated segmentation techniques address the need for MR image analysis in three specific applications:: 1) preclinical rodent studies of primary and metastatic lung cancer: approach: a)),: 2) preclinical rodent studies of spinal cord lesion: approach: b)), and: 3) postclinical analysis of human brain cancer: approach: b)). In preclinical rodent studies of primary and metastatic lung cancer, respiratory-gated MRI is used to quantitatively measure lung-tumor burden and monitor the time-course progression of individual tumors. I validate a method for measuring tumor burden based upon average lung-image intensity. The method requires accurate lung segmentation; toward this end, I propose an automated lung segmentation method that works for varying tumor burden levels. The method includes development of a novel, two-dimensional parametric model of the mouse lungs and a multifaceted cost function to optimally fit the model parameters to each image. Results demonstrate a strong correlation: 0.93), comparable with that of fully manual expert segmentation, between the automated method\u27s tumor-burden metric and the tumor burden measured by lung weight. In preclinical rodent studies of spinal cord lesion, MRI is used to quantify tissues in control and injured mouse spinal cords. For this application, I propose a novel, multistep, multidimensional approach, utilizing the Classification Expectation Maximization: CEM) algorithm, for automatic segmentation of spinal cord tissues. In contrast to previous methods, my proposed method incorporates prior knowledge of cord geometry and the distinct information contained in the different MR images gathered. Unlike previous approaches, the algorithm is shown to remain accurate for whole spinal cord, white matter, and hemorrhage segmentation, even in the presence of significant injury. The results of the method are shown to be on par with expert manual segmentation. In postclinical analysis of human brain cancer, access to large collections of MRI data enables scientifically rigorous study of cancers like glioblastoma multiforme, the most common form of malignant primary brain tumor. For this application, I propose an efficient and effective automated segmentation method, the Enhanced Classification Expectation Maximization: ECEM) algorithm. The ECEM algorithm is novel in that it introduces spatial information directly into the classical CEM algorithm, which is otherwise spatially unaware, with low additional computational complexity. I compare the ECEM\u27s performance on simulated data to the standard finite Gaussian mixture EM algorithm, which is not spatially aware, and to the hidden-Markov random field EM algorithm, a commonly-used spatially aware automated segmentation method for MR brain images. I also show sample results demonstrating the ECEM algorithm\u27s ability to segment MR images of glioblastoma

Image processing for plastic surgery planning

This thesis presents some image processing tools for plastic surgery planning. In particular, it presents a novel method that combines local and global context in a probabilistic relaxation framework to identify cephalometric landmarks used in Maxillofacial plastic surgery. It also uses a method that utilises global and local symmetry to identify abnormalities in CT frontal images of the human body. The proposed methodologies are evaluated with the help of several clinical data supplied by collaborating plastic surgeons

An original framework for understanding human actions and body language by using deep neural networks

The evolution of both fields of Computer Vision (CV) and Artificial Neural Networks (ANNs) has allowed the development of efficient automatic systems for the analysis of people's behaviour. By studying hand movements it is possible to recognize gestures, often used by people to communicate information in a non-verbal way. These gestures can also be used to control or interact with devices without physically touching them. In particular, sign language and semaphoric hand gestures are the two foremost areas of interest due to their importance in Human-Human Communication (HHC) and Human-Computer Interaction (HCI), respectively. While the processing of body movements play a key role in the action recognition and affective computing fields. The former is essential to understand how people act in an environment, while the latter tries to interpret people's emotions based on their poses and movements; both are essential tasks in many computer vision applications, including event recognition, and video surveillance. In this Ph.D. thesis, an original framework for understanding Actions and body language is presented. The framework is composed of three main modules: in the first one, a Long Short Term Memory Recurrent Neural Networks (LSTM-RNNs) based method for the Recognition of Sign Language and Semaphoric Hand Gestures is proposed; the second module presents a solution based on 2D skeleton and two-branch stacked LSTM-RNNs for action recognition in video sequences; finally, in the last module, a solution for basic non-acted emotion recognition by using 3D skeleton and Deep Neural Networks (DNNs) is provided. The performances of RNN-LSTMs are explored in depth, due to their ability to model the long term contextual information of temporal sequences, making them suitable for analysing body movements. All the modules were tested by using challenging datasets, well known in the state of the art, showing remarkable results compared to the current literature methods

Brain Tumor Detection and Segmentation in Multisequence MRI

Tato práce se zabývá detekcí a segmentací mozkového nádoru v multisekvenčních MR obrazech se zaměřením na gliomy vysokého a nízkého stupně malignity. Jsou zde pro tento účel navrženy tři metody. První metoda se zabývá detekcí prezence částí mozkového nádoru v axiálních a koronárních řezech. Jedná se o algoritmus založený na analýze symetrie při různých rozlišeních obrazu, který byl otestován na T1, T2, T1C a FLAIR obrazech. Druhá metoda se zabývá extrakcí oblasti celého mozkového nádoru, zahrnující oblast jádra tumoru a edému, ve FLAIR a T2 obrazech. Metoda je schopna extrahovat mozkový nádor z 2D i 3D obrazů. Je zde opět využita analýza symetrie, která je následována automatickým stanovením intenzitního prahu z nejvíce asymetrických částí. Třetí metoda je založena na predikci lokální struktury a je schopna segmentovat celou oblast nádoru, jeho jádro i jeho aktivní část. Metoda využívá faktu, že většina lékařských obrazů vykazuje vysokou podobnost intenzit sousedních pixelů a silnou korelaci mezi intenzitami v různých obrazových modalitách. Jedním ze způsobů, jak s touto korelací pracovat a používat ji, je využití lokálních obrazových polí. Podobná korelace existuje také mezi sousedními pixely v anotaci obrazu. Tento příznak byl využit v predikci lokální struktury při lokální anotaci polí. Jako klasifikační algoritmus je v této metodě použita konvoluční neuronová síť vzhledem k její známe schopnosti zacházet s korelací mezi příznaky. Všechny tři metody byly otestovány na veřejné databázi 254 multisekvenčních MR obrazech a byla dosáhnuta přesnost srovnatelná s nejmodernějšími metodami v mnohem kratším výpočetním čase (v řádu sekund při použitý CPU), což poskytuje možnost manuálních úprav při interaktivní segmetaci.This work deals with the brain tumor detection and segmentation in multisequence MR images with particular focus on high- and low-grade gliomas. Three methods are propose for this purpose. The first method deals with the presence detection of brain tumor structures in axial and coronal slices. This method is based on multi-resolution symmetry analysis and it was tested for T1, T2, T1C and FLAIR images. The second method deals with extraction of the whole brain tumor region, including tumor core and edema, in FLAIR and T2 images and is suitable to extract the whole brain tumor region from both 2D and 3D. It also uses the symmetry analysis approach which is followed by automatic determination of the intensity threshold from the most asymmetric parts. The third method is based on local structure prediction and it is able to segment the whole tumor region as well as tumor core and active tumor. This method takes the advantage of a fact that most medical images feature a high similarity in intensities of nearby pixels and a strong correlation of intensity profiles across different image modalities. One way of dealing with -- and even exploiting -- this correlation is the use of local image patches. In the same way, there is a high correlation between nearby labels in image annotation, a feature that has been used in the ``local structure prediction'' of local label patches. Convolutional neural network is chosen as a learning algorithm, as it is known to be suited for dealing with correlation between features. All three methods were evaluated on a public data set of 254 multisequence MR volumes being able to reach comparable results to state-of-the-art methods in much shorter computing time (order of seconds running on CPU) providing means, for example, to do online updates when aiming at an interactive segmentation.

Inferring Geodesic Cerebrovascular Graphs: Image Processing, Topological Alignment and Biomarkers Extraction

A vectorial representation of the vascular network that embodies quantitative features - location, direction, scale, and bifurcations - has many potential neuro-vascular applications. Patient-specific models support computer-assisted surgical procedures in neurovascular interventions, while analyses on multiple subjects are essential for group-level studies on which clinical prediction and therapeutic inference ultimately depend. This first motivated the development of a variety of methods to segment the cerebrovascular system. Nonetheless, a number of limitations, ranging from data-driven inhomogeneities, the anatomical intra- and inter-subject variability, the lack of exhaustive ground-truth, the need for operator-dependent processing pipelines, and the highly non-linear vascular domain, still make the automatic inference of the cerebrovascular topology an open problem. In this thesis, brain vessels’ topology is inferred by focusing on their connectedness. With a novel framework, the brain vasculature is recovered from 3D angiographies by solving a connectivity-optimised anisotropic level-set over a voxel-wise tensor field representing the orientation of the underlying vasculature. Assuming vessels joining by minimal paths, a connectivity paradigm is formulated to automatically determine the vascular topology as an over-connected geodesic graph. Ultimately, deep-brain vascular structures are extracted with geodesic minimum spanning trees. The inferred topologies are then aligned with similar ones for labelling and propagating information over a non-linear vectorial domain, where the branching pattern of a set of vessels transcends a subject-specific quantized grid. Using a multi-source embedding of a vascular graph, the pairwise registration of topologies is performed with the state-of-the-art graph matching techniques employed in computer vision. Functional biomarkers are determined over the neurovascular graphs with two complementary approaches. Efficient approximations of blood flow and pressure drop account for autoregulation and compensation mechanisms in the whole network in presence of perturbations, using lumped-parameters analog-equivalents from clinical angiographies. Also, a localised NURBS-based parametrisation of bifurcations is introduced to model fluid-solid interactions by means of hemodynamic simulations using an isogeometric analysis framework, where both geometry and solution profile at the interface share the same homogeneous domain. Experimental results on synthetic and clinical angiographies validated the proposed formulations. Perspectives and future works are discussed for the group-wise alignment of cerebrovascular topologies over a population, towards defining cerebrovascular atlases, and for further topological optimisation strategies and risk prediction models for therapeutic inference. Most of the algorithms presented in this work are available as part of the open-source package VTrails

Development of an Atlas-Based Segmentation of Cranial Nerves Using Shape-Aware Discrete Deformable Models for Neurosurgical Planning and Simulation

Twelve pairs of cranial nerves arise from the brain or brainstem and control our sensory functions such as vision, hearing, smell and taste as well as several motor functions to the head and neck including facial expressions and eye movement. Often, these cranial nerves are difficult to detect in MRI data, and thus represent problems in neurosurgery planning and simulation, due to their thin anatomical structure, in the face of low imaging resolution as well as image artifacts. As a result, they may be at risk in neurosurgical procedures around the skull base, which might have dire consequences such as the loss of eyesight or hearing and facial paralysis. Consequently, it is of great importance to clearly delineate cranial nerves in medical images for avoidance in the planning of neurosurgical procedures and for targeting in the treatment of cranial nerve disorders. In this research, we propose to develop a digital atlas methodology that will be used to segment the cranial nerves from patient image data. The atlas will be created from high-resolution MRI data based on a discrete deformable contour model called 1-Simplex mesh. Each of the cranial nerves will be modeled using its centerline and radius information where the centerline is estimated in a semi-automatic approach by finding a shortest path between two user-defined end points. The cranial nerve atlas is then made more robust by integrating a Statistical Shape Model so that the atlas can identify and segment nerves from images characterized by artifacts or low resolution. To the best of our knowledge, no such digital atlas methodology exists for segmenting nerves cranial nerves from MRI data. Therefore, our proposed system has important benefits to the neurosurgical community

Unsupervised brain anomaly detection in MR images

Brain disorders are characterized by morphological deformations in shape and size of (sub)cortical structures in one or both hemispheres. These deformations cause deviations from the normal pattern of brain asymmetries, resulting in asymmetric lesions that directly affect the patient’s condition. Unsupervised methods aim to learn a model from unlabeled healthy images, so that an unseen image that breaks priors of this model, i.e., an outlier, is considered an anomaly. Consequently, they are generic in detecting any lesions, e.g., coming from multiple diseases, as long as these notably differ from healthy training images. This thesis addresses the development of solutions to leverage unsupervised machine learning for the detection/analysis of abnormal brain asymmetries related to anomalies in magnetic resonance (MR) images. First, we propose an automatic probabilistic-atlas-based approach for anomalous brain image segmentation. Second, we explore an automatic method for the detection of abnormal hippocampi from abnormal asymmetries based on deep generative networks and a one-class classifier. Third, we present a more generic framework to detect abnormal asymmetries in the entire brain hemispheres. Our approach extracts pairs of symmetric regions — called supervoxels — in both hemispheres of a test image under study. One-class classifiers then analyze the asymmetries present in each pair. Experimental results on 3D MR-T1 images from healthy subjects and patients with a variety of lesions show the effectiveness and robustness of the proposed unsupervised approaches for brain anomaly detection