Automatic detection of gadolinium-enhancing multiple sclerosis lesions in brain MRI using conditional random fields.

Gadolinium-enhancing lesions in brain magnetic resonance imaging of multiple sclerosis (MS) patients are of great interest since they are markers of disease activity. Identification of gadolinium-enhancing lesions is particularly challenging because the vast majority of enhancing voxels are associated with normal structures, particularly blood vessels. Furthermore, these lesions are typically small and in close proximity to vessels. In this paper, we present an automatic, probabilistic framework for segmentation of gadolinium-enhancing lesions in MS using conditional random fields. Our approach, through the integration of different components, encodes different information such as correspondence between the intensities and tissue labels, patterns in the labels, or patterns in the intensities. The proposed algorithm is evaluated on 80 multimodal clinical datasets acquired from relapsing-remitting MS patients in the context of multicenter clinical trials. The experimental results exhibit a sensitivity of 98% with a low false positive lesion count. The performance of the proposed algorithm is also compared to a logistic regression classifier, a support vector machine and a Markov random field approach. The results demonstrate superior performance of the proposed algorithm at successfully detecting all of the gadolinium-enhancing lesions while maintaining a low false positive lesion count.

A general framework for analyzing data from two short time-series microarray experiments.

We propose a general theoretical framework for analyzing differentially expressed genes and behavior patterns from two homogenous short time-course data. The framework generalizes the recently proposed Hilbert-Schmidt Independence Criterion (HSIC)-based framework adapting it to the time-series scenario by utilizing tensor analysis for data transformation. The proposed framework is effective in yielding criteria that can identify both the differentially expressed genes and time-course patterns of interest between two time-series experiments without requiring to explicitly cluster the data. The results, obtained by applying the proposed framework with a linear kernel formulation, on various data sets are found to be both biologically meaningful and consistent with published studies.

Evaluating intensity normalization on MRIs of human brain with multiple sclerosis.

Intensity normalization is an important pre-processing step in the study and analysis of Magnetic Resonance Images (MRI) of human brains. As most parametric supervised automatic image segmentation and classification methods base their assumptions regarding the intensity distributions on a standardized intensity range, intensity normalization takes on a very significant role. One of the fast and accurate approaches proposed for intensity normalization is that of Nyul and colleagues. In this work, we present, for the first time, an extensive validation of this approach in real clinical domain where even after intensity inhomogeneity correction that accounts for scanner-specific artifacts, the MRI volumes can be affected from variations such as data heterogeneity resulting from multi-site multi-scanner acquisitions, the presence of multiple sclerosis (MS) lesions and the stage of disease progression in the brain. Using the distributional divergence criteria, we evaluate the effectiveness of the normalization in rendering, under the distributional assumptions of segmentation approaches, intensities that are more homogenous for the same tissue type while simultaneously resulting in better tissue type separation. We also demonstrate the advantage of the decile based piece-wise linear approach on the task of MS lesion segmentation against a linear normalization approach over three image segmentation algorithms: a standard Bayesian classifier, an outlier detection based approach and a Bayesian classifier with Markov Random Field (MRF) based post-processing. Finally, to demonstrate the independence of the effectiveness of normalization from the complexity of segmentation algorithm, we evaluate the Nyul method against the linear normalization on Bayesian algorithms of increasing complexity including a standard Bayesian classifier with Maximum Likelihood parameter estimation and a Bayesian classifier with integrated data priors, in addition to the above Bayesian classifier with MRF based post-processing to smooth the posteriors. In all relevant cases, the observed results are verified for statistical relevance using significance tests.

TRAF6 and IRF7 control HIV replication in macrophages.

The innate immune system recognizes virus infection and evokes antiviral responses which include producing type I interferons (IFNs). The induction of IFN provides a crucial mechanism of antiviral defense by upregulating interferon-stimulated genes (ISGs) that restrict viral replication. ISGs inhibit the replication of many viruses by acting at different steps of their viral cycle. Specifically, IFN treatment prior to in vitro human immunodeficiency virus (HIV) infection stops or significantly delays HIV-1 production indicating that potent inhibitory factors are generated. We report that HIV-1 infection of primary human macrophages decreases tumor necrosis factor receptor-associated factor 6 (TRAF6) and virus-induced signaling adaptor (VISA) expression, which are both components of the IFN signaling pathway controlling viral replication. Knocking down the expression of TRAF6 in macrophages increased HIV-1 replication and augmented the expression of IRF7 but not IRF3. Suppressing VISA had no impact on viral replication. Overexpression of IRF7 resulted in enhanced viral replication while knocking down IRF7 expression in macrophages significantly reduced viral output. These findings are the first demonstration that TRAF6 can regulate HIV-1 production and furthermore that expression of IRF7 promotes HIV-1 replication.

Detection of Gad-enhancing lesions in multiple sclerosis using conditional random fields.

Identification of Gad-enhancing lesions is of great interest in Multiple Sclerosis (MS) disease since they are associated with disease activity. Current techniques for detecting Gad-enhancing lesions use a contrast agent (Gadolinium) which is administered intravenously to highlight Gad-enhancing lesions. However, the contrast agent not only highlights these lesions, but also causes other tissues (e.g., blood vessels) or noise in the Magnetic Resonance Image (MRI) to appear hyperintense. Discrimination of enhanced lesions from other enhanced structures is particularly challenging as these lesions are typically small and can be found in close proximity to vessels. We present a new approach to address the segmentation of Gad-enhancing MS lesions using Conditional Random Fields (CRF). CRF performs the classification by simultaneously incorporating the spatial dependencies of data and labels. The performance of the CRF classifier on 20 clinical data sets shows promising results in successfully capturing all Gad-enhancing lesions. Furthermore, the quantitative results of the CRF classifier indicate a reduction in the False Positive (FP) rate by an average factor of 5.8 when comparing to Linear Discriminant Analysis (LDA) and 1.6 comparing to a Markov Random Field (MRF) classifier.