Quantitative magnetic resonance image analysis via the EM algorithm with stochastic variation

Quantitative Magnetic Resonance Imaging (qMRI) provides researchers insight into pathological and physiological alterations of living tissue, with the help of which researchers hope to predict (local) therapeutic efficacy early and determine optimal treatment schedule. However, the analysis of qMRI has been limited to ad-hoc heuristic methods. Our research provides a powerful statistical framework for image analysis and sheds light on future localized adaptive treatment regimes tailored to the individual's response. We assume in an imperfect world we only observe a blurred and noisy version of the underlying pathological/physiological changes via qMRI, due to measurement errors or unpredictable influences. We use a hidden Markov random field to model the spatial dependence in the data and develop a maximum likelihood approach via the Expectation--Maximization algorithm with stochastic variation. An important improvement over previous work is the assessment of variability in parameter estimation, which is the valid basis for statistical inference. More importantly, we focus on the expected changes rather than image segmentation. Our research has shown that the approach is powerful in both simulation studies and on a real dataset, while quite robust in the presence of some model assumption violations.Comment: Published in at http://dx.doi.org/10.1214/07-AOAS157 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Fast joint detection-estimation of evoked brain activity in event-related fMRI using a variational approach

In standard clinical within-subject analyses of event-related fMRI data, two steps are usually performed separately: detection of brain activity and estimation of the hemodynamic response. Because these two steps are inherently linked, we adopt the so-called region-based Joint Detection-Estimation (JDE) framework that addresses this joint issue using a multivariate inference for detection and estimation. JDE is built by making use of a regional bilinear generative model of the BOLD response and constraining the parameter estimation by physiological priors using temporal and spatial information in a Markovian modeling. In contrast to previous works that use Markov Chain Monte Carlo (MCMC) techniques to approximate the resulting intractable posterior distribution, we recast the JDE into a missing data framework and derive a Variational Expectation-Maximization (VEM) algorithm for its inference. A variational approximation is used to approximate the Markovian model in the unsupervised spatially adaptive JDE inference, which allows fine automatic tuning of spatial regularisation parameters. It follows a new algorithm that exhibits interesting properties compared to the previously used MCMC-based approach. Experiments on artificial and real data show that VEM-JDE is robust to model mis-specification and provides computational gain while maintaining good performance in terms of activation detection and hemodynamic shape recovery

Estimating Time-Varying Effective Connectivity in High-Dimensional fMRI Data Using Regime-Switching Factor Models

Recent studies on analyzing dynamic brain connectivity rely on sliding-window analysis or time-varying coefficient models which are unable to capture both smooth and abrupt changes simultaneously. Emerging evidence suggests state-related changes in brain connectivity where dependence structure alternates between a finite number of latent states or regimes. Another challenge is inference of full-brain networks with large number of nodes. We employ a Markov-switching dynamic factor model in which the state-driven time-varying connectivity regimes of high-dimensional fMRI data are characterized by lower-dimensional common latent factors, following a regime-switching process. It enables a reliable, data-adaptive estimation of change-points of connectivity regimes and the massive dependencies associated with each regime. We consider the switching VAR to quantity the dynamic effective connectivity. We propose a three-step estimation procedure: (1) extracting the factors using principal component analysis (PCA) and (2) identifying dynamic connectivity states using the factor-based switching vector autoregressive (VAR) models in a state-space formulation using Kalman filter and expectation-maximization (EM) algorithm, and (3) constructing the high-dimensional connectivity metrics for each state based on subspace estimates. Simulation results show that our proposed estimator outperforms the K-means clustering of time-windowed coefficients, providing more accurate estimation of regime dynamics and connectivity metrics in high-dimensional settings. Applications to analyzing resting-state fMRI data identify dynamic changes in brain states during rest, and reveal distinct directed connectivity patterns and modular organization in resting-state networks across different states.Comment: 21 page

Automated Knowledge Discovery from Functional Magnetic Resonance Images using Spatial Coherence

Functional Magnetic Resonance Imaging (fMRI) has the potential to unlock many of the mysteries of the brain. Although this imaging modality is popular for brain-mapping activities, clinical applications of this technique are relatively rare. For clinical applications, classification models are more useful than the current practice of reporting loci of neural activation associated with particular disorders. Also, since the methods used to account for anatomical variations between subjects are generally imprecise, the conventional voxel-by-voxel analysis limits the types of discoveries that are possible. This work presents a classification-based framework for knowledge discovery from fMRI data. Instead of voxel-centric knowledge discovery, this framework is segment-centric, where functional segments are clumps of voxels that represent a functional unit in the brain. With simulated activation images, it is shown that this segment-based approach can be more successful for knowledge discovery than conventional voxel-based approaches. The spatial coherence principle refers to the homogeneity of behavior of spatially contiguous voxels. Auto-threshold Contrast Enhancing Iterative Clustering (ACEIC) - a new algorithm based on the spatial coherence principle is presented here for functional segmentation. With benchmark data, it is shown that the ACEIC method can achieve higher segmentation accuracy than Probabilistic Independent Component Analysis - a popular method used for fMRI data analysis. The spatial coherence principle can also be exploited for voxel-centric image-classification problems. Spatially Coherent Voxels (SCV) is a new feature selection method that uses the spatial coherence principle to eliminate features that are unlikely to be useful for classification. For a Substance Use Disorder dataset, it is demonstrated that feature selection with SCV can achieve higher classification accuracies than conventional feature selection methods

ROI-Based Analysis of Functional Imaging Data

In this technical report, we present fMRI analysis techniques that test functional hypotheses at the region of interest (ROI) level. An SPM-compatible Matlab toolbox has been developed which allows the creation of subject-specific ROI masks based on anatomical markers and the testing of functional hypotheses on the regional response using multivariate time-series analysis techniques. The combined application of subject-specific ROI definition and region-level functional analysis is shown to appropriately compensate for inter-subject anatomical variability, offering finer localization and increased sensitivity to task-related effects than standard techniques based on whole brain normalization and voxel or cluster-level functional analysis, while providing a more direct link between discrete brain region hypotheses and the statistical analyses used to test them.National Institute of Health (R29 DC02852, ROI DC02852

Modeling brain dynamics in brain tumor patients using the virtual brain

Presurgical planning for brain tumor resection aims at delineating eloquent tissue in the vicinity of the lesion to spare during surgery. To this end, noninvasive neuroimaging techniques such as functional MRI and diffusion-weighted imaging fiber tracking are currently employed. However, taking into account this information is often still insufficient, as the complex nonlinear dynamics of the brain impede straightforward prediction of functional outcome after surgical intervention. Large-scale brain network modeling carries the potential to bridge this gap by integrating neuroimaging data with biophysically based models to predict collective brain dynamics. As a first step in this direction, an appropriate computational model has to be selected, after which suitable model parameter values have to be determined. To this end, we simulated large-scale brain dynamics in 25 human brain tumor patients and 11 human control participants using The Virtual Brain, an open-source neuroinformatics platform. Local and global model parameters of the Reduced Wong-Wang model were individually optimized and compared between brain tumor patients and control subjects. In addition, the relationship between model parameters and structural network topology and cognitive performance was assessed. Results showed (1) significantly improved prediction accuracy of individual functional connectivity when using individually optimized model parameters; (2) local model parameters that can differentiate between regions directly affected by a tumor, regions distant from a tumor, and regions in a healthy brain; and (3) interesting associations between individually optimized model parameters and structural network topology and cognitive performance

Subject-level Joint Parcellation-Detection-Estimation in fMRI

Brain parcellation is one of the most important issues in functional MRI (fMRI) data analysis. This parcellation allows establishing homogeneous territories that share the same functional properties. This paper presents a model-based approach to perform a subject-level parcellation into hemodynamic territories with similar hemodynamic features which are known to vary between brain regions. We specifically investigate the use of the Joint Parcellation-Detection-Estimation (JPDE) model initially proposed in [1] to separate brain regions that match different hemodynamic response function (HRF) profiles. A hierarchical Bayesian model is built and a variational expectation maximiza-tion (VEM) algorithm is deployed to perform inference. A more complete version of the JPDE model is detailed. Validation on synthetic data shows the robustness of this model to varying signal-to-noise ratio (SNR) as well as to different initializations. Our results also demonstrate that good parcellation performance is achieved even though the parcels do not involve the same amount of activation. On real fMRI data acquired in children during a language paradigm, we retrieved a parcellation along the superior temporal sulcus of the left hemisphere that matches the gradient of activation dynamics already reported in the literature

Learning and comparing functional connectomes across subjects

Functional connectomes capture brain interactions via synchronized fluctuations in the functional magnetic resonance imaging signal. If measured during rest, they map the intrinsic functional architecture of the brain. With task-driven experiments they represent integration mechanisms between specialized brain areas. Analyzing their variability across subjects and conditions can reveal markers of brain pathologies and mechanisms underlying cognition. Methods of estimating functional connectomes from the imaging signal have undergone rapid developments and the literature is full of diverse strategies for comparing them. This review aims to clarify links across functional-connectivity methods as well as to expose different steps to perform a group study of functional connectomes