ACTIVE MEAN FIELDS FOR PROBABILISTIC IMAGE SEGMENTATION: CONNECTIONS WITH CHAN-VESE AND RUDIN-OSHER-FATEMI MODELS.

Segmentation is a fundamental task for extracting semantically meaningful regions from an image. The goal of segmentation algorithms is to accurately assign object labels to each image location. However, image-noise, shortcomings of algorithms, and image ambiguities cause uncertainty in label assignment. Estimating the uncertainty in label assignment is important in multiple application domains, such as segmenting tumors from medical images for radiation treatment planning. One way to estimate these uncertainties is through the computation of posteriors of Bayesian models, which is computationally prohibitive for many practical applications. On the other hand, most computationally efficient methods fail to estimate label uncertainty. We therefore propose in this paper the Active Mean Fields (AMF) approach, a technique based on Bayesian modeling that uses a mean-field approximation to efficiently compute a segmentation and its corresponding uncertainty. Based on a variational formulation, the resulting convex model combines any label-likelihood measure with a prior on the length of the segmentation boundary. A specific implementation of that model is the Chan-Vese segmentation model (CV), in which the binary segmentation task is defined by a Gaussian likelihood and a prior regularizing the length of the segmentation boundary. Furthermore, the Euler-Lagrange equations derived from the AMF model are equivalent to those of the popular Rudin-Osher-Fatemi (ROF) model for image denoising. Solutions to the AMF model can thus be implemented by directly utilizing highly-efficient ROF solvers on log-likelihood ratio fields. We qualitatively assess the approach on synthetic data as well as on real natural and medical images. For a quantitative evaluation, we apply our approach to the icgbench dataset.

Bayesian characterization of uncertainty in intra-subject non-rigid registration.

In settings where high-level inferences are made based on registered image data, the registration uncertainty can contain important information. In this article, we propose a Bayesian non-rigid registration framework where conventional dissimilarity and regularization energies can be included in the likelihood and the prior distribution on deformations respectively through the use of Boltzmann's distribution. The posterior distribution is characterized using Markov Chain Monte Carlo (MCMC) methods with the effect of the Boltzmann temperature hyper-parameters marginalized under broad uninformative hyper-prior distributions. The MCMC chain permits estimation of the most likely deformation as well as the associated uncertainty. On synthetic examples, we demonstrate the ability of the method to identify the maximum a posteriori estimate and the associated posterior uncertainty, and demonstrate that the posterior distribution can be non-Gaussian. Additionally, results from registering clinical data acquired during neurosurgery for resection of brain tumor are provided; we compare the method to single transformation results from a deterministic optimizer and introduce methods that summarize the high-dimensional uncertainty. At the site of resection, the registration uncertainty increases and the marginal distribution on deformations is shown to be multi-modal.

State-space analysis of working memory in schizophrenia: an fBIRN study.

The neural correlates of working memory (WM) in schizophrenia (SZ) have been extensively studied using the multisite fMRI data acquired by the Functional Biomedical Informatics Research Network (fBIRN) consortium. Although univariate and multivariate analysis methods have been variously employed to localize brain responses under differing task conditions, important hypotheses regarding the representation of mental processes in the spatio-temporal patterns of neural recruitment and the differential organization of these mental processes in patients versus controls have not been addressed in this context. This paper uses a multivariate state-space model (SSM) to analyze the differential representation and organization of mental processes of controls and patients performing the Sternberg Item Recognition Paradigm (SIRP) WM task. The SSM is able to not only predict the mental state of the subject from the data, but also yield estimates of the spatial distribution and temporal ordering of neural activity, along with estimates of the hemodynamic response. The dynamical Bayesian modeling approach used in this study was able to find significant differences between the predictability and organization of the working memory processes of SZ patients versus healthy subjects. Prediction of some stimulus types from imaging data in the SZ group was significantly lower than controls, reflecting a greater level of disorganization/heterogeneity of their mental processes. Moreover, the changes in accuracy of predicting the mental state of the subject with respect to parametric modulations, such as memory load and task duration, may have important implications on the neurocognitive models for WM processes in both SZ and healthy adults. Additionally, the SSM was used to compare the spatio-temporal patterns of mental activity across subjects, in a holistic fashion and to derive a low-dimensional representation space for the SIRP task, in which subjects were found to cluster according to their diagnosis.

Time-Resolved and Spatio-Temporal Analysis of Complex Cognitive Processes and their Role in Disorders like Developmental Dyscalculia.

The aim of this article is to report on the importance and challenges of a time-resolved and spatio-temporal analysis of fMRI data from complex cognitive processes and associated disorders using a study on developmental dyscalculia (DD). Participants underwent fMRI while judging the incorrectness of multiplication results, and the data were analyzed using a sequence of methods, each of which progressively provided more a detailed picture of the spatio-temporal aspect of this disease. Healthy subjects and subjects with DD performed alike behaviorally though they exhibited parietal disparities using traditional voxel-based group analyses. Further and more detailed differences, however, surfaced with a time-resolved examination of the neural responses during the experiment. While performing inter-group comparisons, a third group of subjects with dyslexia (DL) but with no arithmetic difficulties was included to test the specificity of the analysis and strengthen the statistical base with overall fifty-eight subjects. Surprisingly, the analysis showed a functional dissimilarity during an initial reading phase for the group of dyslexic but otherwise normal subjects, with respect to controls, even though only numerical digits and no alphabetic characters were presented. Thus our results suggest that time-resolved multi-variate analysis of complex experimental paradigms has the ability to yield powerful new clinical insights about abnormal brain function. Similarly, a detailed compilation of aberrations in the functional cascade may have much greater potential to delineate the core processing problems in mental disorders.

Two solutions for registration of ultrasound to MRI for image-guided prostate interventions.

Ultrasound-guided prostate interventions could benefit from incorporating the radiologic localization of the tumor which can be acquired from multiparametric MRI. To enable this integration, we propose and compare two solutions for registration of T2 weighted MR images with transrectal ultrasound. Firstly, we propose an innovative and practical approach based on deformable registration of binary label maps obtained from manual segmentation of the gland in the two modalities. This resulted in a target registration error of 3.6±1.7 mm. Secondly, we report a novel surface-based registration method that uses a biomechanical model of the tissue and results in registration error of 3.2±1.3 mm. We compare the two methods in terms of accuracy, clinical use and technical limitations.

Selection of optimal hyper-parameters for estimation of uncertainty in MRI-TRUS registration of the prostate.

Transrectal ultrasound (TRUS) facilitates intra-treatment delineation of the prostate gland (PG) to guide insertion of brachytherapy seeds, but the prostate substructure and apex are not always visible which may make the seed placement sub-optimal. Based on an elastic model of the prostate created from MRI, where the prostate substructure and apex are clearly visible, we use a Bayesian approach to estimate the posterior distribution on deformations that aligns the pre-treatment MRI with intra-treatment TRUS. Without apex information in TRUS, the posterior prediction of the location of the prostate boundary, and the prostate apex boundary in particular, is mainly determined by the pseudo stiffness hyper-parameter of the prior distribution. We estimate the optimal value of the stiffness through likelihood maximization that is sensitive to the accuracy as well as the precision of the posterior prediction at the apex boundary. From a data-set of 10 pre- and intra-treatment prostate images with ground truth delineation of the total PG, 4 cases were used to establish an optimal stiffness hyper-parameter when 15% of the prostate delineation was removed to simulate lack of apex information in TRUS, while the remaining 6 cases were used to cross-validate the registration accuracy and uncertainty over the PG and in the apex.

Rapid full-brain fMRI with an accelerated multi shot 3D EPI sequence using both UNFOLD and GRAPPA.

The desire to understand complex mental processes using functional MRI drives development of imaging techniques that scan the whole human brain at a high spatial and temporal resolution. In this work, an accelerated multishot three-dimensional echo-planar imaging sequence is proposed to increase the temporal resolution of these studies. A combination of two modern acceleration techniques, UNFOLD and GRAPPA is used in the secondary phase encoding direction to reduce the scan time effectively. The sequence (repetition time of 1.02 s) was compared with standard two-dimensional echo-planar imaging (3 s) and multishot three-dimensional echo-planar imaging (3 s) sequences with both block design and event-related functional MRI paradigms. With the same experimental setup and imaging time, the temporal resolution improvement with our sequence yields similar activation regions in the block design functional MRI paradigm with slightly increased t-scores. Moreover, additional information on the timing of rapid dynamic changes was extracted from accelerated images for the case of the event related complex mental paradigm.

Non-parametric population analysis of cellular phenotypes.

Methods to quantify cellular-level phenotypic differences between genetic groups are a key tool in genomics research. In disease processes such as cancer, phenotypic changes at the cellular level frequently manifest in the modification of cell population profiles. These changes are hard to detect due the ambiguity in identifying distinct cell phenotypes within a population. We present a methodology which enables the detection of such changes by generating a phenotypic signature of cell populations in a data-derived feature-space. Further, this signature is used to estimate a model for the redistribution of phenotypes that was induced by the genetic change. Results are presented on an experiment involving deletion of a tumor-suppressor gene dominant in breast cancer, where the methodology is used to detect changes in nuclear morphology between control and knockout groups.

Identifying nuclear phenotypes using semi-supervised metric learning.

In systems-based approaches for studying processes such as cancer and development, identifying and characterizing individual cells within a tissue is the first step towards understanding the large-scale effects that emerge from the interactions between cells. To this end, nuclear morphology is an important phenotype to characterize the physiological and differentiated state of a cell. This study focuses on using nuclear morphology to identify cellular phenotypes in thick tissue sections imaged using 3D fluorescence microscopy. The limited label information, heterogeneous feature set describing a nucleus, and existence of subpopulations within cell-types makes this a difficult learning problem. To address these issues, a technique is presented to learn a distance metric from labeled data which is locally adaptive to account for heterogeneity in the data. Additionally, a label propagation technique is used to improve the quality of the learned metric by expanding the training set using unlabeled data. Results are presented on images of tumor stroma in breast cancer, where the framework is used to identify fibroblasts, macrophages and endothelial cells--three major stromal cells involved in carcinogenesis.

State-space models of mental processes from fMRI.

In addition to functional localization and integration, the problem of determining whether the data encode some information about the mental state of the subject, and if so, how this information is represented has become an important research agenda in functional neuroimaging. Multivariate classifiers, commonly used for brain state decoding, are restricted to simple experimental paradigms with a fixed number of alternatives and are limited in their representation of the temporal dimension of the task. Moreover, they learn a mapping from the data to experimental conditions and therefore do not explain the intrinsic patterns in the data. In this paper, we present a data-driven approach to building a spatio-temporal representation of mental processes using a state-space formalism, without reference to experimental conditions. Efficient Monte Carlo algorithms for estimating the parameters of the model along with a method for model-size selection are developed. The advantages of such a model in determining the mental-state of the subject over pattern classifiers are demonstrated using an fMRI study of mental arithmetic.

Spatio-temporal models of mental processes from fMRI.

Understanding the highly complex, spatially distributed and temporally organized phenomena entailed by mental processes using functional MRI is an important research problem in cognitive and clinical neuroscience. Conventional analysis methods focus on the spatial dimension of the data discarding the information about brain function contained in the temporal dimension. This paper presents a fully spatio-temporal multivariate analysis method using a state-space model (SSM) for brain function that yields not only spatial maps of activity but also its temporal structure along with spatially varying estimates of the hemodynamic response. Efficient algorithms for estimating the parameters along with quantitative validations are given. A novel low-dimensional feature-space for representing the data, based on a formal definition of functional similarity, is derived. Quantitative validation of the model and the estimation algorithms is provided with a simulation study. Using a real fMRI study for mental arithmetic, the ability of this neurophysiologically inspired model to represent the spatio-temporal information corresponding to mental processes is demonstrated. Moreover, by comparing the models across multiple subjects, natural patterns in mental processes organized according to different mental abilities are revealed.

Robust 3D reconstruction and identification of dendritic spines from optical microscopy imaging.

In neurobiology, the 3D reconstruction of neurons followed by the identification of dendritic spines is essential for studying neuronal morphology, function and biophysical properties. Most existing methods suffer from problems of low reliability, poor accuracy and require much user interaction. In this paper, we present a method to reconstruct dendrites using a surface representation of the neuron. The skeleton of the dendrite is extracted by a procedure based on the medial geodesic function that is robust and topology preserving, and it is used to accurately identify spines. The sensitivity of the algorithm on the various parameters is explored in detail and the method is shown to be robust.

Tensor classification of N-point correlation function features for histology tissue segmentation.

In this paper, we utilize the N-point correlation functions (N-pcfs) to construct an appropriate feature space for achieving tissue segmentation in histology-stained microscopic images. The N-pcfs estimate microstructural constituent packing densities and their spatial distribution in a tissue sample. We represent the multi-phase properties estimated by the N-pcfs in a tensor structure. Using a variant of higher-order singular value decomposition (HOSVD) algorithm, we realize a robust classifier that provides a multi-linear description of the tensor feature space. Validated results of the segmentation are presented in a case-study that focuses on understanding the genetic phenotyping differences in mouse placentae.

Detection and visualization of surface-pockets to enable phenotyping studies.

In this paper, we propose a technique for detecting pockets on a surface-of-interest. A sequence of propagating fronts converging to the target surface is used as the basis for inspection. We compute a correspondence function between the initial and the target surface. This leads to a natural definition of the local feature size measured as the evolution distance between mapped points. Surface pockets are then extracted as salient clusters embedded in the feature space. The level-set initialization also determines the scale-space of the extracted pockets. Results are presented on a case-study in which the focus is to chronicle the phenotyping differences in genetically modified mouse placenta. Our results are validated based on manually verified ground-truth.