Three-dimensional morphanalysis of the face.

The aim of the work reported in this thesis was to determine the extent to which orthogonal two-dimensional morphanalytic (universally relatable) craniofacial imaging methods can be extended into the realm of computer-based three-dimensional imaging. New methods are presented for capturing universally relatable laser-video surface data, for inter-relating facial surface scans and for constructing probabilistic facial averages. Universally relatable surface scans are captured using the fixed relations principle com- bined with a new laser-video scanner calibration method. Inter- subject comparison of facial surface scans is achieved using inter- active feature labelling and warping methods. These methods have been extended to groups of subjects to allow the construction of three-dimensional probabilistic facial averages. The potential of universally relatable facial surface data for applications such as growth studies and patient assessment is demonstrated. In addition, new methods for scattered data interpolation, for controlling overlap in image warping and a fast, high-resolution method for simulating craniofacial surgery are described. The results demonstrate that it is not only possible to extend universally relatable imaging into three dimensions, but that the extension also enhances the established methods, providing a wide range of new applications

Finite Element Modeling Driven by Health Care and Aerospace Applications

This thesis concerns the development, analysis, and computer implementation of mesh generation algorithms encountered in finite element modeling in health care and aerospace. The finite element method can reduce a continuous system to a discrete idealization that can be solved in the same manner as a discrete system, provided the continuum is discretized into a finite number of simple geometric shapes (e.g., triangles in two dimensions or tetrahedrons in three dimensions). In health care, namely anatomic modeling, a discretization of the biological object is essential to compute tissue deformation for physics-based simulations. This thesis proposes an efficient procedure to convert 3-dimensional imaging data into adaptive lattice-based discretizations of well-shaped tetrahedra or mixed elements (i.e., tetrahedra, pentahedra and hexahedra). This method operates directly on segmented images, thus skipping a surface reconstruction that is required by traditional Computer-Aided Design (CAD)-based meshing techniques and is convoluted, especially in complex anatomic geometries. Our approach utilizes proper mesh gradation and tissue-specific multi-resolution, without sacrificing the fidelity and while maintaining a smooth surface to reflect a certain degree of visual reality. Image-to-mesh conversion can facilitate accurate computational modeling for biomechanical registration of Magnetic Resonance Imaging (MRI) in image-guided neurosurgery. Neuronavigation with deformable registration of preoperative MRI to intraoperative MRI allows the surgeon to view the location of surgical tools relative to the preoperative anatomical (MRI) or functional data (DT-MRI, fMRI), thereby avoiding damage to eloquent areas during tumor resection. This thesis presents a deformable registration framework that utilizes multi-tissue mesh adaptation to map preoperative MRI to intraoperative MRI of patients who have undergone a brain tumor resection. Our enhancements with mesh adaptation improve the accuracy of the registration by more than 5 times compared to rigid and traditional physics-based non-rigid registration, and by more than 4 times compared to publicly available B-Spline interpolation methods. The adaptive framework is parallelized for shared memory multiprocessor architectures. Performance analysis shows that this method could be applied, on average, in less than two minutes, achieving desirable speed for use in a clinical setting. The last part of this thesis focuses on finite element modeling of CAD data. This is an integral part of the design and optimization of components and assemblies in industry. We propose a new parallel mesh generator for efficient tetrahedralization of piecewise linear complex domains in aerospace. CAD-based meshing algorithms typically improve the shape of the elements in a post-processing step due to high complexity and cost of the operations involved. On the contrary, our method optimizes the shape of the elements throughout the generation process to obtain a maximum quality and utilizes high performance computing to reduce the overheads and improve end-user productivity. The proposed mesh generation technique is a combination of Advancing Front type point placement, direct point insertion, and parallel multi-threaded connectivity optimization schemes. The mesh optimization is based on a speculative (optimistic) approach that has been proven to perform well on hardware-shared memory. The experimental evaluation indicates that the high quality and performance attributes of this method see substantial improvement over existing state-of-the-art unstructured grid technology currently incorporated in several commercial systems. The proposed mesh generator will be part of an Extreme-Scale Anisotropic Mesh Generation Environment to meet industries expectations and NASA\u27s CFD visio

THE LEFT HEMISPHERE’S STRUCTURAL CONNECTIVITY FOR THE INFERIOR FRONTAL GYRUS, STRIATUM, AND THALAMUS, AND INTRA-THALAMIC TOPOGRAPHY

The neuroanatomy of language cognition has an extensive history of scientific interest and inquiry. Over a century of behavioral lesion studies and decades of functional neuroimaging research have established the left hemisphere’s inferior frontal gyrus (IFG) as a critical region for speech and language processing. This region’s subcortical projections are thought to be instrumental for supporting and integrating the cognitive functions of the language network. However, only a subset of these projections have been shown to exist in humans, and structural evidence of pars orbitalis’ subcortical circuitry has been limited to non-human primates. This thesis demonstrates direct, intra-structural connectivity of each of the left IFG’s gyral regions with the thalamus and the putamen in humans, using high-angular, deterministic tractography. Novel processing and analysis methods elucidated evidence of predominantly segregated cortical circuits within the thalamus, and suggested the presence of parallel circuits for motor/language integration along the length of the putamen

Assessment of the potentials and limitations of cortical-based analysis for the integration of structure and function in normal and pathological brains using MRI

The software package Brainvisa (www.brainvisa.tnfo) offers a wide range of possibilities for cortical analysis using its automatic sulci recognition feature. Automated sulci identification is an attractive feature as the manual labelling of the cortical sulci is often challenging even for the experienced neuro-radiologists. This can also be of interest in fMRI studies of individual subjects where activated regions of the cortex can simply be identified using sulcal labels without the need for normalization to an atlas. As it will be explained later in this thesis, normalization to atlas can especially be problematic for pathologic brains. In addition, Brainvisa allows for sulcal morphometry from structural MR images by estimating a wide range of sulcal properties such as size, coordinates, direction, and pattern. Morphometry of abnormal brains has gained huge interest and has been widely used in finding the biomarkers of several neurological diseases or psychiatric disorders. However mainly because of its complexity, only a limited use of sulcal morphometry has been reported so far. With a wide range of possibilities for sulcal morphometry offered by Brainvisa, it is possible to thoroughly investigate the sulcal changes due to the abnormality. However, as any other automated method, Brainvisa can be susceptible to limitations associated with image quality. Factors such as noise, spatial resolution, and so on, can have an impact on the detection of the cortical folds and estimation of their attributes. Hence the robustness of Brainvisa needs to be assessed. This can be done by estimating the reliability and reproducibility of results as well as exploring the changes in results caused by other factors. This thesis is an attempt to investigate the possible benefits of sulci identification and sulcal morphometry for functional and structural MRI studies as well as the limitations of Brainvisa. In addition, the possibility of improvement of activation localization with functional MRI studies is further investigated. This investigation was motivated by a review of other cortical-based analysis methods, namely the cortical surface-based methods, which are discussed in the literature review chapter of this thesis. The application of these approaches in functional MRI data analysis and their potential benefits is used in this investigation

Development of Human Body CAD Models and Related Mesh Processing Algorithms with Applications in Bioelectromagnetics

Simulation of the electromagnetic response of the human body relies heavily upon efficient computational CAD models or phantoms. The Visible Human Project (VHP)-Female v. 3.1 - a new platform-independent full-body electromagnetic computational model is revealed. This is a part of a significant international initiative to develop powerful computational models representing the human body. This model’s unique feature is full compatibility both with MATLAB and specialized FEM computational software packages such as ANSYS HFSS/Maxwell 3D and CST MWS. Various mesh processing algorithms such as automatic intersection resolver, Boolean operation on meshes, etc. used for the development of the Visible Human Project (VHP)-Female are presented. The VHP - Female CAD Model is applied to two specific low frequency applications: Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS). TMS and tDCS are increasingly used as diagnostic and therapeutic tools for numerous neuropsychiatric disorders. The development of a CAD model based on an existing voxel model of a Japanese pregnant woman is also presented. TMS for treatment of depression is an appealing alternative to drugs which are teratogenic for pregnant women. This CAD model was used to study fetal wellbeing during induced peak currents by TMS in two possible scenarios: (i) pregnant woman as a patient; and (ii) pregnant woman as an operator. An insight into future work and potential areas of research such as a deformable phantom, implants, and RF applications will be presented

Effect of perinatal adversity on structural connectivity of the developing brain

Globally, preterm birth (defined as birth at <37 weeks of gestation) affects around 11% of deliveries and it is closely associated with cerebral palsy, cognitive impairments and neuropsychiatric diseases in later life. Magnetic Resonance Imaging (MRI) has utility for measuring different properties of the brain during the lifespan. Specially, diffusion MRI has been used in the neonatal period to quantify the effect of preterm birth on white matter structure, which enables inference about brain development and injury. By combining information from both structural and diffusion MRI, is it possible to calculate structural connectivity of the brain. This involves calculating a model of the brain as a network to extract features of interest. The process starts by defining a series of nodes (anatomical regions) and edges (connections between two anatomical regions). Once the network is created, different types of analysis can be performed to find features of interest, thereby allowing group wise comparisons. The main frameworks/tools designed to construct the brain connectome have been developed and tested in the adult human brain. There are several differences between the adult and the neonatal brain: marked variation in head size and shape, maturational processes leading to changes in signal intensity profiles, relatively lower spatial resolution, and lower contrast between tissue classes in the T1 weighted image. All of these issues make the standard processes to construct the brain connectome very challenging to apply in the neonatal population. Several groups have studied the neonatal structural connectivity proposing several alternatives to overcome these limitations. The aim of this thesis was to optimise the different steps involved in connectome analysis for neonatal data. First, to provide accurate parcellation of the cortex a new atlas was created based on a control population of term infants; this was achieved by propagating the atlas from an adult atlas through intermediate childhood spatio-temporal atlases using image registration. After this the advanced anatomically-constrained tractography framework was adapted for the neonatal population, refined using software tools for skull-stripping, tissue segmentation and parcellation specially designed and tested for the neonatal brain. Finally, the method was used to test the effect of early nutrition, specifically breast milk exposure, on structural connectivity in preterm infants. We found that infants with higher exposure to breastmilk in the weeks after preterm birth had improved structural connectivity of developing networks and greater fractional anisotropy in major white matter fasciculi. These data also show that the benefits are dose dependent with higher exposure correlating with increased white matter connectivity. In conclusion, structural connectivity is a robust method to investigate the developing human brain. We propose an optimised framework for the neonatal brain, designed for our data and using tools developed for the neonatal brain, and apply it to test the effect of breastmilk exposure on preterm infants

Towards a data-driven treatment of epilepsy: computational methods to overcome low-data regimes in clinical settings

Epilepsy is the most common neurological disorder, affecting around 1 % of the population. One third of patients with epilepsy are drug-resistant. If the epileptogenic zone can be localized precisely, curative resective surgery may be performed. However, only 40 to 70 % of patients remain seizure-free after surgery. Presurgical evaluation, which in part aims to localize the epileptogenic zone (EZ), is a complex multimodal process that requires subjective clinical decisions, often relying on a multidisciplinary team’s experience. Thus, the clinical pathway could benefit from data-driven methods for clinical decision support. In the last decade, deep learning has seen great advancements due to the improvement of graphics processing units (GPUs), the development of new algorithms and the large amounts of generated data that become available for training. However, using deep learning in clinical settings is challenging as large datasets are rare due to privacy concerns and expensive annotation processes. Methods to overcome the lack of data are especially important in the context of presurgical evaluation of epilepsy, as only a small proportion of patients with epilepsy end up undergoing surgery, which limits the availability of data to learn from. This thesis introduces computational methods that pave the way towards integrating data-driven methods into the clinical pathway for the treatment of epilepsy, overcoming the challenge presented by the relatively small datasets available. We used transfer learning from general-domain human action recognition to characterize epileptic seizures from video–telemetry data. We developed a software framework to predict the location of the epileptogenic zone given seizure semiologies, based on retrospective information from the literature. We trained deep learning models using self-supervised and semi-supervised learning to perform quantitative analysis of resective surgery by segmenting resection cavities on brain magnetic resonance images (MRIs). Throughout our work, we shared datasets and software tools that will accelerate research in medical image computing, particularly in the field of epilepsy

Synthesization and reconstruction of 3D faces by deep neural networks

The past few decades have witnessed substantial progress towards 3D facial modelling and reconstruction as it is high importance for many computer vision and graphics applications including Augmented/Virtual Reality (AR/VR), computer games, movie post-production, image/video editing, medical applications, etc. In the traditional approaches, facial texture and shape are represented as triangle mesh that can cover identity and expression variation with non-rigid deformation. A dataset of 3D face scans is then densely registered into a common topology in order to construct a linear statistical model. Such models are called 3D Morphable Models (3DMMs) and can be used for 3D face synthesization or reconstruction by a single or few 2D face images. The works presented in this thesis focus on the modernization of these traditional techniques in the light of recent advances of deep learning and thanks to the availability of large-scale datasets. Ever since the introduction of 3DMMs by over two decades, there has been a lot of progress on it and they are still considered as one of the best methodologies to model 3D faces. Nevertheless, there are still several aspects of it that need to be upgraded to the "deep era". Firstly, the conventional 3DMMs are built by linear statistical approaches such as Principal Component Analysis (PCA) which omits high-frequency information by its nature. While this does not curtail shape, which is often smooth in the original data, texture models are heavily afflicted by losing high-frequency details and photorealism. Secondly, the existing 3DMM fitting approaches rely on very primitive (i.e. RGB values, sparse landmarks) or hand-crafted features (i.e. HOG, SIFT) as supervision that are sensitive to "in-the-wild" images (i.e. lighting, pose, occlusion), or somewhat missing identity/expression resemblance with the target image. Finally, shape, texture, and expression modalities are separately modelled by ignoring the correlation among them, placing a fundamental limit to the synthesization of semantically meaningful 3D faces. Moreover, photorealistic 3D face synthesis has not been studied thoroughly in the literature. This thesis attempts to address the above-mentioned issues by harnessing the power of deep neural network and generative adversarial networks as explained below: Due to the linear texture models, many of the state-of-the-art methods are still not capable of reconstructing facial textures with high-frequency details. For this, we take a radically different approach and build a high-quality texture model by Generative Adversarial Networks (GANs) that preserves details. That is, we utilize GANs to train a very powerful generator of facial texture in the UV space. And then show that it is possible to employ this generator network as a statistical texture prior to 3DMM fitting. The resulting texture reconstructions are plausible and photorealistic as GANs are faithful to the real-data distribution in both low- and high- frequency domains. Then, we revisit the conventional 3DMM fitting approaches making use of non-linear optimization to find the optimal latent parameters that best reconstruct the test image but under a new perspective. We propose to optimize the parameters with the supervision of pretrained deep identity features through our end-to-end differentiable framework. In order to be robust towards initialization and expedite the fitting process, we also propose a novel self-supervised regression-based approach. We demonstrate excellent 3D face reconstructions that are photorealistic and identity preserving and achieve for the first time, to the best of our knowledge, facial texture reconstruction with high-frequency details. In order to extend the non-linear texture model for photo-realistic 3D face synthesis, we present a methodology that generates high-quality texture, shape, and normals jointly. To do so, we propose a novel GAN that can generate data from different modalities while exploiting their correlations. Furthermore, we demonstrate how we can condition the generation on the expression and create faces with various facial expressions. Additionally, we study another approach for photo-realistic face synthesis by 3D guidance. This study proposes to generate 3D faces by linear 3DMM and then augment their 2D rendering by an image-to-image translation network to the photorealistic face domain. Both works demonstrate excellent photorealistic face synthesis and show that the generated faces are improving face recognition benchmarks as synthetic training data. Finally, we study expression reconstruction for personalized 3D face models where we improve generalization and robustness of expression encoding. First, we propose a 3D augmentation approach on 2D head-mounted camera images to increase robustness to perspective changes. And, we also propose to train generic expression encoder network by populating the number of identities with a novel multi-id personalized model training architecture in a self-supervised manner. Both approaches show promising results in both qualitative and quantitative experiments.Open Acces

Hybrid PET/MRI Nanoparticle Development and Multi-Modal Imaging

The development of hybrid PET/MRI imaging systems needs to be paralleled with the development of a hybrid intrinsic PET/MRI probes. The aim of this work was to develop and validate a novel radio-superparamagnetic nanoparticle (r-SPNP) for hybrid PET/MRI imaging. This was achieved with the synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) that intrinsically incorporated 59Fe and manganese iron oxide nanoparticles (MIONs) that intrinsically incorporated 52Mn. Both [59Fe]-SPIONs and [52Mn]-MIONs were produced through thermal decomposition synthesis. The physiochemical characteristics of the r-SPNPs were assessed with TEM, DLS, and zeta-potential measurements, as well as in imaging phantom studies. The [59Fe]-SPIONs were evaluated in vivo with biodistribution and MR imaging studies. The biodistrubution studies of [59Fe]-SPIONs showed uptake in the liver. This corresponded with major MR signal contrast measured in the liver. 52Mn was produced on natural chromium through the 52Cr(p,n)52Mn reaction. The manganese radionuclides were separated from the target material through a liquid-liquid extraction. The αVβ3 integrin binding of [52Mn]-MION-cRGDs was evaluated with αVβ3 integrin solid phase assays, and the expression of αVβ3 integrin in U87MG xenograft tumors was characterized with fluorescence flow cytometry. [52Mn]-MION-cRGDs were used for in vivo PET and MR imaging of U87MG xenograft tumor bearing mice. PET data showed increased [52Mn]-MION-cRGD uptake compared with untargeted [52Mn]-MIONs. ROI analysis of PET and MRI data showed that MR contrasted corresponded with PET signal. Future work will utilize [52Mn]-MION-cRGDs in other tumor models and with hybrid PET/MRI imaging systems