MyoScreen, a High-Throughput Phenotypic Screening Platform Enabling Muscle Drug Discovery.

Despite the need for more effective drug treatments to address muscle atrophy and disease, physiologically accurate in vitro screening models and higher information content preclinical assays that aid in the discovery and development of novel therapies are lacking. To this end, MyoScreen was developed: a robust and versatile high-throughput high-content screening (HT/HCS) platform that integrates a physiologically and pharmacologically relevant micropatterned human primary skeletal muscle model with a panel of pertinent phenotypic and functional assays. MyoScreen myotubes form aligned, striated myofibers, and they show nerve-independent accumulation of acetylcholine receptors (AChRs), excitation-contraction coupling (ECC) properties characteristic of adult skeletal muscle and contraction in response to chemical stimulation. Reproducibility and sensitivity of the fully automated MyoScreen platform are highlighted in assays that quantitatively measure myogenesis, hypertrophy and atrophy, AChR clusterization, and intracellular calcium release dynamics, as well as integrating contractility data. A primary screen of 2560 compounds to identify stimulators of myofiber regeneration and repair, followed by further biological characterization of two hits, validates MyoScreen for the discovery and testing of novel therapeutics. MyoScreen is an improvement of current in vitro muscle models, enabling a more predictive screening strategy for preclinical selection of the most efficacious new chemical entities earlier in the discovery pipeline process.

Compressed Sensing Doppler Ultrasound Reconstruction Using Block Sparse Bayesian Learning.

In this paper we propose a framework for using duplex Doppler ultrasound systems. These type of systems need to interleave the acquisition and display of a B-mode image and of the pulsed Doppler spectrogram. In a recent study (Richy , 2013), we have shown that compressed sensing-based reconstruction of Doppler signal allowed reducing the number of Doppler emissions and yielded better results than traditional interpolation and at least equivalent or even better depending on the configuration than the study estimating the signal from sparse data sets given in Jensen, 2006. We propose here to improve over this study by using a novel framework for randomly interleaving Doppler and US emissions. The proposed method reconstructs the Doppler signal segment by segment using a block sparse Bayesian learning (BSBL) algorithm based CS reconstruction. The interest of using such framework in the context of duplex Doppler is linked to the unique ability of BSBL to exploit block-correlated signals and to recover non-sparse signals. The performance of the technique is evaluated from simulated data as well as experimental in vivo data and compared to the recent results in Richy , 2013.

Compressed Sensing Reconstruction of 3D Ultrasound Data Using Dictionary Learning and Line-Wise Subsampling.

In this paper we present a compressed sensing (CS) method adapted to 3D ultrasound imaging (US). In contrast to previous work, we propose a new approach based on the use of learned overcomplete dictionaries that allow for much sparser representations of the signals since they are optimized for a particular class of images such as US images. In this study, the dictionary was learned using the K-SVD algorithm and CS reconstruction was performed on the non-log envelope data by removing 20% to 80% of the original data. Using numerically simulated images, we evaluate the influence of the training parameters and of the sampling strategy. The latter is done by comparing the two most common sampling patterns, i.e., point-wise and line-wise random patterns. The results show in particular that line-wise sampling yields an accuracy comparable to the conventional point-wise sampling. This indicates that CS acquisition of 3D data is feasible in a relatively simple setting, and thus offers the perspective of increasing the frame rate by skipping the acquisition of RF lines. Next, we evaluated this approach on US volumes of several ex vivo and in vivo organs. We first show that the learned dictionary approach yields better performances than conventional fixed transforms such as Fourier or discrete cosine. Finally, we investigate the generality of the learned dictionary approach and show that it is possible to build a general dictionary allowing to reliably reconstruct different volumes of different ex vivo or in vivo organs.