Doctor of Philosophy

dissertationRecent developments in magnetic resonance imaging (MRI) provide an in vivo and noninvasive tool for studying the human brain. In particular, the detection of anisotropic diffusion in biological tissues provides the foundation for diffusion-weighted imaging (DWI), an MRI modality. This modality opens new opportunities for discoveries of the brain's structural connections. Clinically, DWI is often used to analyze white matter tracts to understand neuropsychiatric disorders and the connectivity of the central nervous system. However, due to imaging time required, DWI used in clinical studies has a low angular resolution. In this dissertation, we aim to accurately track and segment the white matter tracts and estimate more representative models from low angular DWI. We first present a novel geodesic approach to segmentation of white matter tracts from diffusion tensor imaging (DTI), estimated from DWI. Geodesic approaches treat the geometry of brain white matter as a manifold, often using the inverse tensor field as a Riemannian metric. The white matter pathways are then inferred from the resulting geodesics. A serious drawback of current geodesic methods is that geodesics tend to deviate from the major eigenvectors in high-curvature areas in order to achieve the shortest path. We propose a method for learning an adaptive Riemannian metric from the DTI data, where the resulting geodesics more closely follow the principal eigenvector of the diffusion tensors even in high-curvature regions. Using the computed geodesics, we develop an automatic way to compute binary segmentations of the white matter tracts. We demonstrate that our method is robust to noise and results in improved geodesics and segmentations. Then, based on binary segmentations, we present a novel Bayesian approach for fractional segmentation of white matter tracts and simultaneous estimation of a multitensor diffusion model. By incorporating a prior that assumes the tensor fields inside each tract are spatially correlated, we are able to reliably estimate multiple tensor compartments in fiber crossing regions, even with low angular diffusion-weighted imaging. This reduces the effects of partial voluming and achieves a more reliable analysis of diffusion measurements

Radiotherapy planning for glioblastoma based on a tumor growth model: Improving target volume delineation

Glioblastoma are known to infiltrate the brain parenchyma instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In clinical practice, a uniform margin is applied to account for microscopic spread of disease. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth: Anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher-Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. A retrospective study involving 10 glioblastoma patients has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most crucial model input. We conclude that the tumor growth model provides a method to account for anisotropic growth patterns of glioblastoma, and may therefore provide a tool to make target delineation more objective and automated

A hitchhiker's guide to diffusion tensor imaging

Diffusion Tensor Imaging (DTI) studies are increasingly popular among clinicians and researchers as they provide unique insights into brain network connectivity. However, in order to optimize the use of DTI, several technical and methodological aspects must be factored in. These include decisions on: acquisition protocol, artifact handling, data quality control, reconstruction algorithm, and visualization approaches, and quantitative analysis methodology. Furthermore, the researcher and/or clinician also needs to take into account and decide on the most suited software tool(s) for each stage of the DTI analysis pipeline. Herein, we provide a straightforward hitchhiker's guide, covering all of the workflow's major stages. Ultimately, this guide will help newcomers navigate the most critical roadblocks in the analysis and further encourage the use of DTI.The work was supported by SwitchBox-FP7-HEALTH-2010-grant 259772-2. The authors acknowledge Nadine Santos for her help in editing the manuscript

Concussion classification via deep learning using whole-brain white matter fiber strains

Developing an accurate and reliable injury predictor is central to the biomechanical studies of traumatic brain injury. State-of-the-art efforts continue to rely on empirical, scalar metrics based on kinematics or model-estimated tissue responses explicitly pre-defined in a specific brain region of interest. They could suffer from loss of information. A single training dataset has also been used to evaluate performance but without cross-validation. In this study, we developed a deep learning approach for concussion classification using implicit features of the entire voxel-wise white matter fiber strains. Using reconstructed American National Football League (NFL) injury cases, leave-one-out cross-validation was employed to objectively compare injury prediction performances against two baseline machine learning classifiers (support vector machine (SVM) and random forest (RF)) and four scalar metrics via univariate logistic regression (Brain Injury Criterion (BrIC), cumulative strain damage measure of the whole brain (CSDM-WB) and the corpus callosum (CSDM-CC), and peak fiber strain in the CC). Feature-based deep learning and machine learning classifiers consistently outperformed all scalar injury metrics across all performance categories in cross-validation (e.g., average accuracy of 0.844 vs. 0.746, and average area under the receiver operating curve (AUC) of 0.873 vs. 0.769, respectively, based on the testing dataset). Nevertheless, deep learning achieved the best cross-validation accuracy, sensitivity, and AUC (e.g., accuracy of 0.862 vs. 0.828 and 0.842 for SVM and RF, respectively). These findings demonstrate the superior performances of deep learning in concussion prediction, and suggest its promise for future applications in biomechanical investigations of traumatic brain injury.Comment: 18 pages, 7 figures, and 4 table

The Examination of White Matter Microstructure, Autism Traits, and Social Cognitive Abilities in Neurotypical Adults

The purpose of this study was to examine the relationships among mentalizing abilities, self-reported autism traits, and two white matter tracts, uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF), in neurotypical adults. UF and ILF were hypothesized to connect brain regions implicated in a neuroanatomical model of mentalizing. Data were available for 24 neurotypical adults (mean age = 21.92 (4.72) years; 15 women). Tract-based spatial statistics (TBSS) was used to conduct voxelwise cross-participant comparisons of fractional anisotropy (FA) values in UF and ILF as predicted by mentalizing abilities and self-reported autism traits. Self-reported autism traits were positively related to FA values in left ILF. Results suggest that microstructural differences in left ILF are specifically involved in the expression of subclinical autism traits in neurotypical individuals

Uncertainty-aware Visualization in Medical Imaging - A Survey

Medical imaging (image acquisition, image transformation, and image visualization) is a standard tool for clinicians in order to make diagnoses, plan surgeries, or educate students. Each of these steps is affected by uncertainty, which can highly influence the decision-making process of clinicians. Visualization can help in understanding and communicating these uncertainties. In this manuscript, we aim to summarize the current state-of-the-art in uncertainty-aware visualization in medical imaging. Our report is based on the steps involved in medical imaging as well as its applications. Requirements are formulated to examine the considered approaches. In addition, this manuscript shows which approaches can be combined to form uncertainty-aware medical imaging pipelines. Based on our analysis, we are able to point to open problems in uncertainty-aware medical imaging

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

Evaluation of machine learning algorithms for treatment outcome prediction in patients with epilepsy based on structural connectome data

The objective of this study is to evaluate machine learning algorithms aimed at predicting surgical treatment outcomes in groups of patients with temporal lobe epilepsy (TLE) using only the structural brain connectome. Specifically, the brain connectome is reconstructed using white matter fiber tracts from presurgical diffusion tensor imaging. To achieve our objective, a two-stage connectome-based prediction framework is developed that gradually selects a small number of abnormal network connections that contribute to the surgical treatment outcome, and in each stage a linear kernel operation is used to further improve the accuracy of the learned classifier. Using a 10-fold cross validation strategy, the first stage in the connectome-based framework is able to separate patients with TLE from normal controls with 80% accuracy, and second stage in the connectome-based framework is able to correctly predict the surgical treatment outcome of patients with TLE with 70% accuracy. Compared to existing state-of-the-art methods that use VBM data, the proposed two-stage connectome-based prediction framework is a suitable alternative with comparable prediction performance. Our results additionally show that machine learning algorithms that exclusively use structural connectome data can predict treatment outcomes in epilepsy with similar accuracy compared with "expert-based" clinical decision. In summary, using the unprecedented information provided in the brain connectome, machine learning algorithms may uncover pathological changes in brain network organization and improve outcome forecasting in the context of epilepsy

Whole-brain white matter correlates of personality profiles predictive of subjective well-being.

We investigated the white matter correlates of personality profiles predictive of subjective well-being. Using principal component analysis to first determine the possible personality profiles onto which core personality measures would load, we subsequently searched for whole-brain white matter correlations with these profiles. We found three personality profiles that correlated with the integrity of white matter tracts. The correlates of an "optimistic" personality profile suggest (a) an intricate network for self-referential processing that helps regulate negative affect and maintain a positive outlook on life, (b) a sustained capacity for visually tracking rewards in the environment and (c) a motor readiness to act upon the conviction that desired rewards are imminent. The correlates of a "short-term approach behavior" profile was indicative of minimal loss of integrity in white matter tracts supportive of lifting certain behavioral barriers, possibly allowing individuals to act more outgoing and carefree in approaching people and rewards. Lastly, a "long-term approach behavior" profile's association with white matter tracts suggests lowered sensitivity to transient updates of stimulus-based associations of rewards and setbacks, thus facilitating the successful long-term pursuit of goals. Together, our findings yield convincing evidence that subjective well-being has its manifestations in the brain