Nonsupervised Ranking of Different Segmentation Approaches: Application to the Estimation of the Left Ventricular Ejection Fraction From Cardiac Cine MRI Sequences

International audienceA statistical methodology is proposed to rank several estimation methods of a relevant clinical parameter when no gold standard is available. Based on a regression without truth method, the proposed approach was applied to rank eightmethods without using any a priori information regarding the reliability of each method and its degree of automation. It was only based on a prior concerning the statistical distribution of the parameter of interest in the database. The ranking of the methods relies on figures of merit derived from the regression and computed using a bootstrap process. The methodology was applied to the estimation of the left ventricular ejection fraction derived from cardiac magnetic resonance images segmented using eight approaches with different degrees of automation: three segmentations were entirely manually performed and the others were variously automated. The ranking of methods was consistent with the expected performance of the estimation methods: the most accurate estimates of the ejection fraction were obtained using manual segmentations. The robustness of the ranking was demonstrated when at least three methods were compared. These results suggest that the proposed statistical approach might be helpful to assess the performance of estimation methods on clinical data for which no gold standard is available

Comparison of different segmentation approaches without using gold standard. Application to the estimation of the left ventricle ejection fraction from cardiac cine MRI sequences.

International audienceA statistical method is proposed to compare several estimates of a relevant clinical parameter when no gold standard is available. The method is illustrated by considering the left ventricle ejection fraction derived from cardiac magnetic resonance images and computed using seven approaches with different degrees of automation. The proposed method did not use any a priori regarding with the reliability of each method and its degree of automation. The results showed that the most accurate estimates of the ejection fraction were obtained using manual segmentations, followed by the semiautomatic methods, while the methods with the least user input yielded the least accurate ejection fraction estimates. These results were consistent with the expected performance of the estimation methods, suggesting that the proposed statistical approach might be helpful to assess the performance of estimation methods on clinical data for which no gold standard is available

Improved estimation of the left ventricular ejection fraction using a combination of independent automated segmentation results in cardiovascular magnetic resonance imaging

—This work aimed at combining different segmenta-tion approaches to produce a robust and accurate segmentation result. Three to five segmentation results of the left ventricle were combined using the STAPLE algorithm and the reliability of the resulting segmentation was evaluated in comparison with the result of each individual segmentation method. This comparison was performed using a supervised approach based on a reference method. Then, we used an unsupervised statistical evaluation, the extended Regression Without Truth (eRWT) that ranks different methods according to their accuracy in estimating a specific biomarker in a population. The segmentation accuracy was evaluated by focusing on the left ventricular ejection fraction (LVEF) estimate resulting from the LV contour delineation using a public cardiac cine MRI database. Eight different segmentation methods, including three expert delineations, were studied, and sixteen combinations of the five automated methods were investigated. The supervised and unsupervised evaluations demonstrated that in most cases, STAPLE results provided better estimates of the LVEF than individual automated segmentation methods. In addition, LVEF obtained with STAPLE were within inter-expert variability. Overall, combining different automated segmentation methods improved the reliability of the segmenta-tion result compared to that obtained using an individual metho

Metabolomic profile of neuroendocrine tumors (NETs) identifies methionine, porphyrin and tryptophan metabolism as key dysregulated pathways associated with patient survival

Objective: Metabolic profiling is a valuable tool to characterize tumor biology but remains largely unexplored in neuroendocrine tumors (NETs). Our aim was to comprehensively assess the metabolomic profile of NETs and identify novel prognostic biomarkers and dysregulated molecular pathways.Design and Methods: Multiplatform untargeted metabolomic profiling (GC-MS, CE-MS, and LC-MS) was performed in plasma from 77 patients with G1-2 extra-pancreatic NETs enrolled in the AXINET trial (NCT01744249) (study cohort) and from 68 non-cancer individuals (control). The prognostic value of each differential metabolite (n = 155) in NET patients (P < .05) was analyzed by univariate and multivariate analyses adjusted for multiple testing and other confounding factors. Related pathways were explored by Metabolite Set Enrichment Analysis (MSEA) and Metabolite Pathway Analysis (MPA).Results: Thirty-four metabolites were significantly associated with progression-free survival (PFS) (n = 16) and/or overall survival (OS) (n = 27). Thirteen metabolites remained significant independent prognostic factors in multivariate analysis, 3 of them with a significant impact on both PFS and OS. Unsupervised clustering of these 3 metabolites stratified patients in 3 distinct prognostic groups (1-year PFS of 71.1%, 47.7%, and 15.4% (P = .012); 5-year OS of 69.7%, 32.5%, and 27.7% (P = .003), respectively). The MSEA and MPA of the 13-metablolite signature identified methionine, porphyrin, and tryptophan metabolisms as the 3 most relevant dysregulated pathways associated with the prognosis of NETs.Conclusions: We identified a metabolomic signature that improves prognostic stratification of NET patients beyond classical prognostic factors for clinical decisions. The enriched metabolic pathways identified reveal novel tumor vulnerabilities that may foster the development of new therapeutic strategies for these patients

Loss of Hairless Confers Susceptibility to UVB-Induced Tumorigenesis via Disruption of NF-kappaB Signaling

In order to model squamous cell carcinoma development in vivo, researchers have long preferred hairless mouse models such as SKH-1 mice that have traditionally been classified as ‘wild-type’ mice irrespective of the genetic factors underlying their hairless phenotype. The work presented here shows that mutations in the Hairless (Hr) gene not only result in the hairless phenotype of the SKH-1 and Hr−/− mouse lines but also cause aberrant activation of NFκB and its downstream effectors. We show that in the epidermis, Hr is an early UVB response gene that regulates NFκB activation and thereby controls cellular responses to irradiation. Therefore, when Hr expression is decreased in Hr mutant animals there is a corresponding increase in NFκB activity that is augmented by UVB irradiation. This constitutive activation of NFκB in the Hr mutant epidermis leads to the stimulation a large variety of downstream effectors including the cell cycle regulators cyclin D1 and cyclin E, the anti-apoptosis protein Bcl-2, and the pro-inflammatory protein Cox-2. Therefore, Hr loss results in a state of uncontrolled epidermal proliferation that promotes tumor development, and Hr mutant mice should no longer be considered merely hairless 'wild-type' mice. Instead, Hr is a crucial UVB response gene and its loss creates a permissive environment that potentiates increased tumorigenesis

Consistency of impact assessment protocols for non-native species

Standardized tools are needed to identify and prioritize the most harmful non-native species (NNS). A plethora of assessment protocols have been developed to evaluate the current and potential impacts of non-native species, but consistency among them has received limited attention. To estimate the consistency across impact assessment protocols, 89 specialists in biological invasions used 11 protocols to screen 57 NNS (2614 assessments). We tested if the consistency in the impact scoring across assessors, quantified as the coefficient of variation (CV), was dependent on the characteristics of the protocol, the taxonomic group and the expertise of the assessor. Mean CV across assessors was 40%, with a maximum of 223%. CV was lower for protocols with a low number of score levels, which demanded high levels of expertise, and when the assessors had greater expertise on the assessed species. The similarity among protocols with respect to the final scores was higher when the protocols considered the same impact types. We conclude that all protocols led to considerable inconsistency among assessors. In order to improve consistency, we highlight the importance of selecting assessors with high expertise, providing clear guidelines and adequate training but also deriving final decisions collaboratively by consensus

Regulation of WRN protein cellular localization and enzymatic activities by SIRT1-mediated deacetylation

Werner syndrome is an autosomal recessive disorder associated with premature aging and cancer predisposition caused by mutations of the WRN gene. WRN is a member of the RecQ DNA helicase family with functions in maintaining genome stability. Sir2, an NAD-dependent histone deacetylase, has been proven to extend life span in yeast and Caenorhabditis elegans. Mammalian Sir2 (SIRT1) has also been found to regulate premature cellular senescence induced by the tumor suppressors PML and p53. SIRT1 plays an important role in cell survival promoted by calorie restriction. Here we show that SIRT1 interacts with WRN both in vitro and in vivo; this interaction is enhanced after DNA damage. WRN can be acetylated by acetyltransferase CBP/p300, and SIRT1 can deacetylate WRN both in vitro and in vivo. WRN acetylation decreases its helicase and exonuclease activities, and SIRT1 can reverse this effect. WRN acetylation alters its nuclear distribution. Down-regulation of SIRT1 reduces WRN translocation from nucleoplasm to nucleoli after DNA damage. These results suggest that SIRT1 regulates WRN-mediated cellular responses to DNA damage through deacetylation of WRN

Estimation d'une forme mutuelle pour l'évaluation de la segmentation en imagerie cardiaque

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Méthodologie Pour Comparer Différentes Méthodes D'extraction De Biomarqueurs Sans Méthode De Référence. Application À La Segmentation Du Ventricule Gauche En Irm Cardiaque Pour Estimer La Fraction D'éjection.

International audienceUne méthodologie est proposée pour comparer plusieurs méthodes d’estimation d’un paramètre d’intérêt clinique sans connaître de gold standard. Elle est appliquée à un problème de comparaison de la fraction d’éjection du ventricule gauche en IRM cardiaque obtenue par sept approches de segmentation différentes et appliquée à 30 examens issus de la base de données constituée pour le challenge Miccai 2009 de segmentation du ventricule gauche. La comparaison des méthodes montre une supériorité du tracé manuel, un bon comportement des méthodes de segmentation semi-automatiques et un plus mauvais comportement des méthodes plus largement automatisées. La méthodologie de comparaison proposée qui ne fait aucun a priori sur les méthodes retrouve ainsi l’ordre attendu. Cette approche méthodologique est donc pertinente et doit permettre une classification non supervisée de différentes méthodes d’estimation de biomarqueurs

<i>Hairless</i> mutant epidermis shows constitutive activation of the NFκB signaling pathway.

<p>A) Western Blot and ImageJ densitometry analysis using anti-p65 antibody on isolated <i>Hr^−/−</i> epidermal extracts after 1, 8 and 24 hrs post UVB (180 mJ/cm²) irradiation. B) Immunohistochemistry using p-IκBα antibody to determine the extent of NFκB signaling activity in the epidermis of WT (<i>Hr^+/+</i>) and <i>Hr^−/−</i> animals before and after a single, acute UVB (180 mJ/cm²) irradiation. IκBα is increased constitutively and after irradiation throughout the epidermal layer. C) Immunohistochemistry using p-IκBα antibody to determine the extent of NFκB signaling activity in the epidermis of WT (<i>Hr^+/+</i>) and <i>Hr^−/−</i> animals at the indicated time points during chronic UVB irradiation (180 mJ/cm² UVB three times a week for a total of 50 weeks). IκBα is increased constitutively and after irradiation throughout the epidermal layer.</p