a-live-cell-image-based-machine-learning-strategy-to-monitor

A Live-cell Image-Based Machine Learning Strategy to Monitor Pluripotent Stem Cell Differentiation

Pluripotent stem cell (PSC) technologies have been widely used in drug discovery, disease modeling, and regenerative medicine.&#160;However, available ...

Peking University

The differentiation of pluripotent stem cells (PSCs) into diverse functional cell types provides a promising solution to support drug discovery, disease modeling, and regenerative medicine. However, functional cell differentiation is currently limited by the substantial line-to-line and batch-to-batch variabilities, which severely impede the progress of scientific research and the manufacturing of cell products. For instance, PSC-to-cardiomyocyte (CM) differentiation is vulnerable to inappropriate doses of CHIR99021 (CHIR) that are applied in the initial stage of mesoderm differentiation. Here, by harnessing live-cell bright-field imaging and machine learning (ML), we realize real-time cell recognition in the entire differentiation process, e.g., CMs, cardiac progenitor cells (CPCs), PSC clones, and even misdifferentiated cells. This enables non-invasive prediction of differentiation efficiency, purification of ML-recognized CMs and CPCs for reducing cell contamination, early assessment of the CHIR dose for correcting the misdifferentiation trajectory, and evaluation of initial PSC colonies for controlling the start point of differentiation, all of which provide a more invulnerable differentiation method with resistance to variability. Moreover, with the established ML models as a readout for the chemical screen, we identify a CDK8 inhibitor that can further improve the cell resistance to the overdose of CHIR. Together, this study indicates that artificial intelligence is able to guide and iteratively optimize PSC differentiation to achieve consistently high efficiency across cell lines and batches, providing a better understanding and rational modulation of the differentiation process for functional cell manufacturing in biomedical applications.

A live-cell image-based machine learning strategy for reducing variability in PSC differentiation systems.

&#xD;Blood flow sensitivity is a crucial metric for appraising the effectiveness of color Doppler flow imaging (CDFI). Color Doppler velocity maps based on classic autocorrelation techniques are widely used in clinical practice. However, these techniques often produce twinkling artifacts in noisy regions due to the inherent randomness of noise phases. To mitigate artifacts and improve image quality, Power Mask (PoM) technology becomes imperative. Nevertheless, PoM technology unintentionally filters out small flow signals that have similar power and frequency characteristics to noise signals, thereby reducing the imaging system's sensitivity to flow. &#xD;Approach:&#xD;To address this issue, a novel Flow Recycling Algorithm (FRA) based on phase anomaly is introduced in this study. This algorithm, excavating small flow signals from noise, aims to enhance the small flow signals with low-velocity by the phase characteristics of the color Doppler flow information. &#xD;Main results: &#xD;Experiments in multi-organ imaging have shown that the FRA-CDFI approach is more effective in suppressing twinkling artifacts in noisy regions, preserving intricate small flow signals, and markedly improving small blood flow sensitivity. This novel approach provides adequate technical support for clinical ultrasound imaging of organs with dense small blood vessels, such as the brain, kidneys, liver, and more. &#xD;Significance: &#xD;As a novel post-processing method, FRA-CDFI holds significant potential for future deployment in clinical high-frame-rate ultrasound imaging devices.

Article	Year
A live-cell image-based machine learning strategy for reducing variability in PSC differentiation systems. Cell discovery\| PubMed ID: 37280224	2023
Improving microvascular sensitivity of color doppler using phase mask based flow recycling algorithm. Physics in medicine and biology\| PubMed ID: 39357539	2024

Daichao Chen

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