Multi-Modal Glioblastoma Segmentation: Man versus Machine

Background and Purpose

Reproducible segmentation of brain tumors on magnetic resonance images is an important clinical need. This study was designed to evaluate the reliability of a novel fully automated segmentation tool for brain tumor image analysis in comparison to manually defined tumor segmentations.

Methods

We prospectively evaluated preoperative MR Images from 25 glioblastoma patients. Two independent expert raters performed manual segmentations. Automatic segmentations were performed using the Brain Tumor Image Analysis software (BraTumIA). In order to study the different tumor compartments, the complete tumor volume TV (enhancing part plus non-enhancing part plus necrotic core of the tumor), the TV+ (TV plus edema) and the contrast enhancing tumor volume CETV were identified. We quantified the overlap between manual and automated segmentation by calculation of diameter measurements as well as the Dice coefficients, the positive predictive values, sensitivity, relative volume error and absolute volume error.

Results

Comparison of automated versus manual extraction of 2-dimensional diameter measurements showed no significant difference (p = 0.29). Comparison of automated versus manual segmentation of volumetric segmentations showed significant differences for TV+ and TV (p<0.05) but no significant differences for CETV (p>0.05) with regard to the Dice overlap coefficients. Spearman''s rank correlation coefficients (ρ) of TV+, TV and CETV showed highly significant correlations between automatic and manual segmentations. Tumor localization did not influence the accuracy of segmentation.

Conclusions

In summary, we demonstrated that BraTumIA supports radiologists and clinicians by providing accurate measures of cross-sectional diameter-based tumor extensions. The automated volume measurements were comparable to manual tumor delineation for CETV tumor volumes, and outperformed inter-rater variability for overlap and sensitivity.     

MakeHub:Fully Automated Generation of UCSC Genome Browser Assembly Hubs

Novel genomes are today often annotated by small consortia or individuals whose background is not from bioinformatics.This audience requires tools that are easy to use.Such need has been addressed by several genome annotation tools and pipelines.Visualizing resulting annotation is a crucial step of quality control.The UCSC Genome Browser is a powerful and popular genome visualization tool.Assembly Hubs,which can be hosted on any publicly available web server,allow browsing genomes via UCSC Genome Browser servers.The steps for creating custom Assembly Hubs are well documented and the required tools are publicly available.However,the number of steps for creating a novel Assembly Hub is large.In some cases,the format of input files needs to be adapted,which is a difficult task for scientists without programming background.Here,we describe Make Hub,a novel command line tool that generates Assembly Hubs for the UCSC Genome Browser in a fully automated fashion.The pipeline also allows extending previously created Hubs by additional tracks.Make Hub is freely available for downloading at https://github.com/Gaius-Augustus/Make Hub.     

Fred W. McLafferty: The Man Who Drove a Different Kind of Flying Machine

The Protein Journal -     

Diffusion-Weighted Imaging in 3.0 Tesla Breast MRI: Diagnostic Performance and Tumor Characterization Using Small Subregions vs. Whole Tumor Regions of Interest

Introduction

Apparent diffusion coefficient (ADC) values are increasingly reported in breast MRI. As there is no standardized method for ADC measurements, we evaluated the effect of the size of region of interest (ROI) to diagnostic utility and correlation to prognostic markers of breast cancer.

Methods

This prospective study was approved by the Institutional Ethics Board; the need for written informed consent for the retrospective analyses of the breast MRIs was waived by the Chair of the Hospital District. We compared diagnostic accuracy of ADC measurements from whole-lesion ROIs (WL-ROIs) to small subregions (S-ROIs) showing the most restricted diffusion and evaluated correlations with prognostic factors in 112 consecutive patients (mean age 56.2±11.6 years, 137 lesions) who underwent 3.0-T breast MRI.

Results

Intra- and interobserver reproducibility were substantial (κ = 0.616–0.784; Intra-Class Correlation 0.589–0.831). In receiver operating characteristics analysis, differentiation between malignant and benign lesions was excellent (area under curve 0.957–0.962, cut-off ADC values for WL-ROIs: 0.87×10⁻³ mm²s^-1; S-ROIs: 0.69×10⁻³ mm²s^-1, P<0.001). WL-ROIs/S-ROIs achieved sensitivities of 95.7%/91.3%, specificities of 89.5%/94.7%, and overall accuracies of 89.8%/94.2%. In S-ROIs, lower ADC values correlated with presence of axillary metastases (P = 0.03), high histological grade (P = 0.006), and worsened Nottingham Prognostic Index Score (P<0.05). In both ROIs, ADC values correlated with progesterone receptors and advanced stage (P<0.01), but not with HER2, estrogen receptors, or Ki-67.

Conclusions

ADC values assist in breast tumor characterization. Small ROIs were more accurate than whole-lesion ROIs and more frequently associated with prognostic factors. Cut-off values differed significantly depending on measurement procedure, which should be recognized when comparing results from the literature. Instead of using a whole lesion covering ROI, a small ROI could be advocated in diffusion-weighted imaging.     

A Fully Automated Microfluidic Femtosecond Laser Axotomy Platform for Nerve Regeneration Studies in C. elegans

Femtosecond laser nanosurgery has been widely accepted as an axonal injury model, enabling nerve regeneration studies in the small model organism, Caenorhabditis elegans. To overcome the time limitations of manual worm handling techniques, automation and new immobilization technologies must be adopted to improve throughput in these studies. While new microfluidic immobilization techniques have been developed that promise to reduce the time required for axotomies, there is a need for automated procedures to minimize the required amount of human intervention and accelerate the axotomy processes crucial for high-throughput. Here, we report a fully automated microfluidic platform for performing laser axotomies of fluorescently tagged neurons in living Caenorhabditis elegans. The presented automation process reduces the time required to perform axotomies within individual worms to ∼17 s/worm, at least one order of magnitude faster than manual approaches. The full automation is achieved with a unique chip design and an operation sequence that is fully computer controlled and synchronized with efficient and accurate image processing algorithms. The microfluidic device includes a T-shaped architecture and three-dimensional microfluidic interconnects to serially transport, position, and immobilize worms. The image processing algorithms can identify and precisely position axons targeted for ablation. There were no statistically significant differences observed in reconnection probabilities between axotomies carried out with the automated system and those performed manually with anesthetics. The overall success rate of automated axotomies was 67.4±3.2% of the cases (236/350) at an average processing rate of 17.0±2.4 s. This fully automated platform establishes a promising methodology for prospective genome-wide screening of nerve regeneration in C. elegans in a truly high-throughput manner.     

Association Test Based on SNP Set: Logistic Kernel Machine Based Test vs. Principal Component Analysis

GWAS has facilitated greatly the discovery of risk SNPs associated with complex diseases. Traditional methods analyze SNP individually and are limited by low power and reproducibility since correction for multiple comparisons is necessary. Several methods have been proposed based on grouping SNPs into SNP sets using biological knowledge and/or genomic features. In this article, we compare the linear kernel machine based test (LKM) and principal components analysis based approach (PCA) using simulated datasets under the scenarios of 0 to 3 causal SNPs, as well as simple and complex linkage disequilibrium (LD) structures of the simulated regions. Our simulation study demonstrates that both LKM and PCA can control the type I error at the significance level of 0.05. If the causal SNP is in strong LD with the genotyped SNPs, both the PCA with a small number of principal components (PCs) and the LKM with kernel of linear or identical-by-state function are valid tests. However, if the LD structure is complex, such as several LD blocks in the SNP set, or when the causal SNP is not in the LD block in which most of the genotyped SNPs reside, more PCs should be included to capture the information of the causal SNP. Simulation studies also demonstrate the ability of LKM and PCA to combine information from multiple causal SNPs and to provide increased power over individual SNP analysis. We also apply LKM and PCA to analyze two SNP sets extracted from an actual GWAS dataset on non-small cell lung cancer.     

A Review of Frailty Analysis in Older Adults: From Clinical Tools Towards Fully Automated Preventive Systems

ObjectivesFrailty is a geriatric syndrome characterized by sarcopenia and physiological impairment. Although the majority of older adults wish to age at home, being frail threatens this choice since it increases the risk of falls and loss of functional independence. Hence, frailty screening and early detection are needed to stop or at least slow down the physical weakening process. In this paper, we present a review in which we discuss the proposed methods from the literature that targets frailty detection and analysis, starting from traditional clinical tools then introducing data-driven studies before highlighting the importance of fully automated systems.Material and methodsWe conducted a review study by searching several databases such as Google Scholar, IEEE Xplore, MDPI, and ScienceDirect to name a few. This work presents clinical tools and classical performance tests to assess the health status and the physical function, as well as statistical and observational studies to analyze the frailty syndrome. Moreover, we discuss briefly the work of our research team in this context, represented by the development of a telemonitoring system which aims at the transition from a curative to a preventive model.ResultsFirstly, this review points out the absence of a gold standard to detect frailty in older individuals. Secondly, it discusses the limitations of self-reported measures/questionnaires and other traditional performance tests which are based on subjective data and done under supervised conditions. Thirdly, our study emphasizes the lack of robust approaches that target the early detection of frailty and the prediction of a future risk of physical worsening. We propose new research directions based, on the one hand, on automatic activity identification and tracking and, on the other hand, on the analysis of spontaneous speech of elderly.ConclusionThis paper describes research findings and highlights the existing gaps in the context of frailty, and serves as a state of the art for researchers. Additionally, this work suggests future research directions regarding the early detection and prevention of frailty.     

Compartmentalization of prostaglandins and prostacyclin within the kidney: implications for renal function.

When renal function is compromised, the circulation to the kidney is sustained by a major prostaglandin component, withdrawal of which results in significant hemodynamic effects, particularly reduction in blood flow to the inner cortex and medulla. Prostaglandins modulate the effects of vasoactive hormones by attenuating the renal actions of the renin-angiotensin system and contributing to and, perhaps, mediating some of those of the kallikreinkinin system. In addition, a prostaglandin mechanism, presumably located in the renal arterioles, participates in the regulation of renin release. Although cyclooxygenase is present in several renal tissues, the major products of arachidonic acid metabolism may be tissue specific and, consequently, their effects may be primarily restricted to one compartment, e.g., the proposed interaction of prostacyclin and renin within the vascular pole of the glomerulus; and PGE2/PGF2a with the kallikrein-kinin system within the urinary compartment. The former is related to the regulation of renin release and renal vascular resistance and the latter to the excretion of water and perhaps salt.