Development of automated annotation software for human embryo morphokinetics.

STUDY QUESTION: Is it possible to develop an automated annotation tool for human embryo development in time-lapse devices based on image analysis? SUMMARY ANSWER: We developed and validated an automated software for the annotation of human embryo morphokinetic parameters, having a good concordance with expert manual annotation on 701 time-lapse videos. WHAT IS KNOWN ALREADY: Morphokinetic parameters obtained with time-lapse devices are increasingly used for the assessment of human embryo quality. However, their annotation is time-consuming and can be slightly operator-dependent, highlighting the need to develop fully automated approaches. STUDY DESIGN, SIZE, DURATION: This monocentric study was conducted on 701 videos originating from 584 couples undergoing IVF with embryo culture in a time-lapse device. The only selection criterion was that the duration of the video must be over 60 h. PARTICIPANTS/MATERIALS, SETTING, METHODS: An automated morphokinetic annotation tool was developed based on gray level coefficient of variation and detection of the thickness of the zona pellucida. The detection of cellular events obtained with the automated tool was compared with those obtained manually by trained experts in clinical settings. MAIN RESULTS AND THE ROLE OF CHANCE: Although some differences were found when embryos were considered individually, we found an overall concordance between automated and manual annotation of human embryo morphokinetics from fertilization to expanded blastocyst stage (r2 = 0.92). LIMITATIONS, REASONS FOR CAUTION: These results should undergo multicentric external evaluation in order to test the overall performance of the annotation tool. Getting access to the export of 3D videos would enhance the quality of the correlation with the same algorithm and its extension to the 3D regions of interest. A technical limitation of our work lies within the duration of the video. The more embryo stages the video contains, the more information the script has to identify them correctly. WIDER IMPLICATIONS OF THE FINDINGS: Our system paves the way for high-throughput analysis of multicentric morphokinetic databases, providing new insights into the clinical value of morphokinetics as a predictor of embryo quality and implantation. STUDY FUNDING/COMPETING INTEREST(S): This study was partly funded by Finox-Gedeon Richter Forward Grant 2016 and NeXT (ANR-16-IDEX-0007). We have no conflict of interests to declare. TRIAL REGISTRATION NUMBER: N/A.

In-vitro validation of 4D flow MRI measurements with an experimental pulsatile flow model.

PURPOSE: The purpose of this study was to assess the precision of four-dimensional (4D) phase-contrast magnetic resonance imaging (PCMRI) to measure mean flow and peak velocity (Vmax) in a pulsatile flow phantom and to test its sensitivity to spatial resolution and Venc. MATERIAL AND METHODS: The pulsatile flow phantom consisted of a straight tube connected to the systemic circulation of an experimental mock circulatory system. Four-dimensional-PCMR images were acquired using different spatial resolutions (minimum pixel size: 1.5×1.5×1.5mm3) and velocity encoding sensitivities (up to three times Vmax). Mean flow and Vmax calculated from 4D-PCMRI were compared respectively to the reference phantom flow parameters and to Vmax obtained from two-dimensional (2D)-PCMRI. RESULTS: 4D-PCI measured mean flow with a precision of -0.04% to+5.46%, but slightly underestimated Vmax when compared to 2D-PCMRI (differences ranging from -1.71% to -3.85%). 4D PCMRI mean flow measurement was influenced by spatial resolution (P<0.001) with better results obtained with smaller voxel size. There was no effect of Venc on mean flow measurement. Regarding Vmax, neither spatial resolution nor Venc did influence the precision of the measurement. CONCLUSION: Using an experimental pulsatile flow model 4D-PCMRI is accurate to measure mean flow and Vmax with better results obtained with higher spatial resolution. We also show that Venc up to 3 times higher than Vmax may be used with no effect on these measurements.

L. fermentum CECT 5716 prevents stress-induced intestinal barrier dysfunction in newborn rats.

BACKGROUND: Intestinal epithelial barrier (IEB) dysfunction plays a critical role in various intestinal disorders affecting infants and children, including the development of food allergies and colitis. Recent studies highlighted the role of probiotics in regulating IEB functions and behavior in adults, but their effects in the newborn remain largely unknown. We therefore characterized in rat pups, the impact of Lactobacillus fermentum CECT 5716 (L. fermentum) on stress-induced IEB dysfunction, systemic immune response and exploratory behavior. METHODS: Newborn rats received daily by gavage either L. fermentum or water. Intestinal permeability to fluorescein sulfonic acid (FSA) and horseradish peroxidase (HRP) was measured following maternal separation (MS) and water avoidance stress (WAS). Immunohistochemical, transcriptomic, and Western blot analysis of zonula occludens-1 (ZO-1) distribution and expression were performed. Anxiety-like and exploratory behavior was assessed using the elevated plus maze test. Cytokine secretion of activated splenocytes was also evaluated. KEY RESULTS: L. fermentum prevented MS and WAS-induced IEB dysfunction in vivo. L. fermentum reduced permeability to both FSA and HRP in the small intestine but not in the colon. L. fermentum increased expression of ZO-1 and prevented WAS-induced ZO-1 disorganization in ileal epithelial cells. L. fermentum also significantly reduced stress-induced increase in plasma corticosteronemia. In activated splenocytes, L. fermentum enhanced IFNγ secretion while it prevented IL-4 secretion. Finally, L. fermentum increased exploratory behavior. CONCLUSIONS & INFERENCES: These results suggest that L. fermentum could provide a novel tool for the prevention and/or treatment of gastrointestinal disorders associated with altered IEB functions in the newborn.