Low-Rank Atlas Image Analyses in the Presence of Pathologies

We present a common framework, for registering images to an atlas and for forming an unbiased atlas, that tolerates the presence of pathologies such as tumors and traumatic brain injury lesions. This common framework is particularly useful when a sufficient number of protocol-matched scans from healthy subjects cannot be easily acquired for atlas formation and when the pathologies in a patient cause large appearance changes

Low-Rank Based Image Analyses for Pathological MR Image Segmentation and Recovery

The presence of pathologies in magnetic resonance (MR) brain images causes challenges in various image analysis areas, such as registration, atlas construction and atlas-based segmentation. We propose a novel method for the simultaneous recovery and segmentation of pathological MR brain images. Low-rank and sparse decomposition (LSD) approaches have been widely used in this field, decomposing pathological images into (1) low-rank components as recovered images, and (2) sparse components as pathological segmentation. However, conventional LSD approaches often fail to produce recovered images reliably, due to the lack of constraint between low-rank and sparse components. To tackle this problem, we propose a transformed low-rank and structured sparse decomposition (TLS2D) method. The proposed TLS2D integrates the structured sparse constraint, LSD and image alignment into a unified scheme, which is robust for distinguishing pathological regions. Furthermore, the well recovered images can be obtained using TLS2D with the combined structured sparse and computed image saliency as the adaptive sparsity constraint. The efficacy of the proposed method is verified on synthetic and real MR brain tumor images. Experimental results demonstrate that our method can effectively provide satisfactory image recovery and tumor segmentation

Robust whole-brain segmentation: Application to traumatic brain injury

We propose a framework for the robust and fully-automatic segmentation of magnetic resonance (MR) brain images called "Multi-Atlas Label Propagation with Expectation-Maximisation based refinement" (MALP-EM). The presented approach is based on a robust registration approach (MAPER), highly performant label fusion (joint label fusion) and intensity-based label refinement using EM. We further adapt this framework to be applicable for the segmentation of brain images with gross changes in anatomy. We propose to account for consistent registration errors by relaxing anatomical priors obtained by multi-atlas propagation and a weighting scheme to locally combine anatomical atlas priors and intensity-refined posterior probabilities. The method is evaluated on a benchmark dataset used in a recent MICCAI segmentation challenge. In this context we show that MALP-EM is competitive for the segmentation of MR brain scans of healthy adults when compared to state-of-the-art automatic labelling techniques. To demonstrate the versatility of the proposed approach, we employed MALP-EM to segment 125 MR brain images into 134 regions from subjects who had sustained traumatic brain injury (TBI). We employ a protocol to assess segmentation quality if no manual reference labels are available. Based on this protocol, three independent, blinded raters confirmed on 13 MR brain scans with pathology that MALP-EM is superior to established label fusion techniques. We visually confirm the robustness of our segmentation approach on the full cohort and investigate the potential of derived symmetry-based imaging biomarkers that correlate with and predict clinically relevant variables in TBI such as the Marshall Classification (MC) or Glasgow Outcome Score (GOS). Specifically, we show that we are able to stratify TBI patients with favourable outcomes from non-favourable outcomes with 64.7% accuracy using acute-phase MR images and 66.8% accuracy using follow-up MR images. Furthermore, we are able to differentiate subjects with the presence of a mass lesion or midline shift from those with diffuse brain injury with 76.0% accuracy. The thalamus, putamen, pallidum and hippocampus are particularly affected. Their involvement predicts TBI disease progression.This work was partially funded under the 7th Framework Programme by the European Commission (http://cordis.europa.eu/ist/, TBIcare: http://www.tbicare.eu/, last accessed: 8 December 2014). The research was further supported by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London. AH is supported by the Department of Health via the NIHR comprehensive BRC award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and Kings College Hospital NHS Foundation Trust. This work was further supported by a Medical Research Council (UK) Program Grant (Acute brain injury: heterogeneity of mechanisms, therapeutic targets and outcome effects [G9439390 ID 65883]), the UK National Institute of Health Research Biomedical Research Centre at Cambridge, the Technology Platform funding provided by the UK Department of Health and an EPSRC Pathways to Impact award. VFJN is supported by a Health Foundation/Academy of Medical Sciences Clinician Scientist Fellowship. DKM is supported by an NIHR Senior Investigator Award. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The funders had no role in study design, data collection and analyses, decision to publish, or preparation of the manuscript

A segmentation editing framework based on shape change statistics

Segmentation is a key task in medical image analysis because its accuracy significantly affects successive steps. Automatic segmentation methods often produce inadequate segmentations, which require the user to manually edit the produced segmentation slice by slice. Because editing is time-consuming, an editing tool that enables the user to produce accurate segmentations by only drawing a sparse set of contours would be needed. This paper describes such a framework as applied to a single object. Constrained by the additional information enabled by the manually segmented contours, the proposed framework utilizes object shape statistics to transform the failed automatic segmentation to a more accurate version. Instead of modeling the object shape, the proposed framework utilizes shape change statistics that were generated to capture the object deformation from the failed automatic segmentation to its corresponding correct segmentation. An optimization procedure was used to minimize an energy function that consists of two terms, an external contour match term and an internal shape change regularity term. The high accuracy of the proposed segmentation editing approach was confirmed by testing it on a simulated data set based on 10 in-vivo infant magnetic resonance brain data sets using four similarity metrics. Segmentation results indicated that our method can provide efficient and adequately accurate segmentations (Dice segmentation accuracy increase of 10%), with very sparse contours (only 10%), which is promising in greatly decreasing the work expected from the user

WWOX sensitises ovarian cancer cells to paclitaxel via modulation of the ER stress response

There are clear gaps in our understanding of genes and pathways through which cancer cells facilitate survival strategies as they become chemoresistant. Paclitaxel is used in the treatment of many cancers, but development of drug resistance is common. Along with being an antimitotic agent paclitaxel also activates endoplasmic reticulum (ER) stress. Here, we examine the role of WWOX (WW domain containing oxidoreductase), a gene frequently lost in several cancers, in mediating paclitaxel response. We examine the ER stress-mediated apoptotic response to paclitaxel in WWOX-transfected epithelial ovarian cancer (EOC) cells and following siRNA knockdown of WWOX. We show that WWOX-induced apoptosis following exposure of EOC cells to paclitaxel is related to ER stress and independent of the antimitotic action of taxanes. The apoptotic response to ER stress induced by WWOX re-expression could be reversed by WWOX siRNA in EOC cells. We report that paclitaxel treatment activates both the IRE-1 and PERK kinases and that the increase in paclitaxel-mediated cell death through WWOX is dependent on active ER stress pathway. Log-rank analysis of overall survival (OS) and progression-free survival (PFS) in two prominent EOC microarray data sets (Tothill and The Cancer Genome Atlas), encompassing ~800 patients in total, confirmed clinical relevance to our findings. High WWOX mRNA expression predicted longer OS and PFS in patients treated with paclitaxel, but not in patients who were treated with only cisplatin. The association of WWOX and survival was dependent on the expression level of glucose-related protein 78 (GRP78), a key ER stress marker in paclitaxel-treated patients. We conclude that WWOX sensitises EOC to paclitaxel via ER stress-induced apoptosis, and predicts clinical outcome in patients. Thus, ER stress response mechanisms could be targeted to overcome chemoresistance in cancer

Structure-based predictions broadly link transcription factor mutations to gene expression changes in cancers

© 2014 The Author(s). Thousands of unique mutations in transcription factors (TFs) arise in cancers, and the functional and biological roles of relatively few of these have been characterized. Here, we used structure-based methods developed specifically for DNA-binding proteins to systematically predict the consequences of mutations in several TFs that are frequently mutated in cancers. The explicit consideration of protein-DNA interactions was crucial to explain the roles and prevalence of mutations in TP53 and RUNX1 in cancers, and resulted in a higher specificity of detection for known p53-regulated genes among genetic associations between TP53 genotypes and genome-wide expression in The Cancer Genome Atlas, compared to existing methods of mutation assessment. Biophysical predictions also indicated that the relative prevalence of TP53 missense mutations in cancer is proportional to their thermodynamic impacts on protein stability and DNA binding, which is consistent with the selection for the loss of p53 transcriptional function in cancers. Structure and thermodynamics-based predictions of the impacts of missense mutations that focus on specific molecular functions may be increasingly useful for the precise and large-scale inference of aberrant molecular phenotypes in cancer and other complex diseases