Unrolled three-operator splitting for parameter-map learning in Low Dose X-ray CT reconstruction

We propose a method for fast and automatic estimation of spatially dependent regularization maps for total variation-based (TV) tomography reconstruction. The estimation is based on two distinct sub-networks, with the first sub-network estimating the regularization parameter-map from the input data while the second one unrolling T iterations of the Primal-Dual Three-Operator Splitting (PD3O) algorithm. The latter approximately solves the corresponding TV-minimization problem incorporating the previously estimated regularization parameter-map. The overall network is then trained end-to-end in a supervised learning fashion using pairs of clean-corrupted data but crucially without the need of having access to labels for the optimal regularization parameter-maps

Learning Regularization Parameter-Maps for Variational Image Reconstruction Using Deep Neural Networks and Algorithm Unrolling

We introduce a method for the fast estimation of data-adapted, spatially and temporally dependent regularization parameter-maps for variational image reconstruction, focusing on total variation (TV) minimization. The proposed approach is inspired by recent developments in algorithm unrolling using deep neural networks (NNs) and relies on two distinct subnetworks. The first subnetwork estimates the regularization parameter-map from the input data. The second subnetwork unrolls iterations of an iterative algorithm which approximately solves the corresponding TV-minimization problem incorporating the previously estimated regularization parameter-map. The overall network is then trained end-to-end in a supervised learning fashion using pairs of clean and corrupted data but crucially without the need for access to labels for the optimal regularization parameter-maps. We first prove consistency of the unrolled scheme by showing that the unrolled minimizing energy functional used for the supervised learning -converges, as tends to infinity, to the corresponding functional that incorporates the exact solution map of the TV-minimization problem. Then, we apply and evaluate the proposed method on a variety of large-scale and dynamic imaging problems with retrospectively simulated measurement data for which the automatic computation of such regularization parameters has been so far challenging using the state-of-the-art methods: a 2D dynamic cardiac magnetic resonance imaging (MRI) reconstruction problem, a quantitative brain MRI reconstruction problem, a low-dose computed tomography problem, and a dynamic image denoising problem. The proposed method consistently improves the TV reconstructions using scalar regularization parameters, and the obtained regularization parameter-maps adapt well to imaging problems and data by leading to the preservation of detailed features. Although the choice of the regularization parameter-maps is data-driven and based on NNs, the subsequent reconstruction algorithm is interpretable since it inherits the properties (e.g., convergence guarantees) of the iterative reconstruction method from which the network is implicitly defined

Nanoelectropulse-driven membrane perturbation and small molecule permeabilization

BACKGROUND: Nanosecond, megavolt-per-meter pulsed electric fields scramble membrane phospholipids, release intracellular calcium, and induce apoptosis. Flow cytometric and fluorescence microscopy evidence has associated phospholipid rearrangement directly with nanoelectropulse exposure and supports the hypothesis that the potential that develops across the lipid bilayer during an electric pulse drives phosphatidylserine (PS) externalization. RESULTS: In this work we extend observations of cells exposed to electric pulses with 30 ns and 7 ns durations to still narrower pulse widths, and we find that even 3 ns pulses are sufficient to produce responses similar to those reported previously. We show here that in contrast to unipolar pulses, which perturb membrane phospholipid order, tracked with FM1-43 fluorescence, only at the anode side of the cell, bipolar pulses redistribute phospholipids at both the anode and cathode poles, consistent with migration of the anionic PS head group in the transmembrane field. In addition, we demonstrate that, as predicted by the membrane charging hypothesis, a train of shorter pulses requires higher fields to produce phospholipid scrambling comparable to that produced by a time-equivalent train of longer pulses (for a given applied field, 30, 4 ns pulses produce a weaker response than 4, 30 ns pulses). Finally, we show that influx of YO-PRO-1, a fluorescent dye used to detect early apoptosis and activation of the purinergic P2X(7 )receptor channels, is observed after exposure of Jurkat T lymphoblasts to sufficiently large numbers of pulses, suggesting that membrane poration occurs even with nanosecond pulses when the electric field is high enough. Propidium iodide entry, a traditional indicator of electroporation, occurs with even higher pulse counts. CONCLUSION: Megavolt-per-meter electric pulses as short as 3 ns alter the structure of the plasma membrane and permeabilize the cell to small molecules. The dose responses of cells to unipolar and bipolar pulses ranging from 3 ns to 30 ns duration support the hypothesis that a field-driven charging of the membrane dielectric causes the formation of pores on a nanosecond time scale, and that the anionic phospholipid PS migrates electrophoretically along the wall of these pores to the external face of the membrane

Nuclear receptors in human immune cells: expressions and correlations

Nuclear receptors (NR) are key modulators of gene transcription. Their activity is ligand induced and modulates a large variety of tissue-specific cellular functions. However, for many NR little is known about their role in cells of the immune system. In this study, expression patterns and distribution of 24 NR were investigated in human peripheral blood mononuclear cells.We provide the first evidence of the expression of the 12 receptors CAR, CoupTF , CoupTF , FXR, GCNF, HNF4 , PPAR / , PXR, RevErb , TR2, TR4 and TLX in highly purified CD4, CD8, CD19, CD14 cells. The expression profile of RevErb and LXR previously observed in B cell and macrophages, respectively, has been extended to CD4, CD8 and CD14 cells. Except for RAR , which was absence in any of the cells tested, our results suggest an almost ubiquitous expression of the NR in the different cell lineages of the immune system. The expression of CAR, CoupTF , FXR was also confirmed at a protein level and despite conspicuous mRNA levels of HNF4 , only low levels of this receptor were detectable in the nuclear fraction of PBMCs. Expression of the latter receptors was mostly only a fraction (4–20%) of their expression in the thyroid gland, the adrenal gland, the lung or subcutaneous adipose tissue. The Spearman rank order correlation test was performed to examine the correlation in expression between individual nuclear receptor pairs in the four cell types for several donors. Distinct correlation patterns were observed between receptor pairs in the individual cell types. In CD4 T cells four NR, GCNF, PPAR , PPAR 7 and RevErb are perfectly correlated with each other (P≥0.0167). In the other cell types correlations betweenNRpairs were more diverse, but also statistically highly significant. Interestingly, the relative expression level of a number of receptor pairs ranked identical or similar in at least three (CoupTF and PPAR / , CoupTF andHNF4 as well asROR and PXR) or four cell types (CoupTF and CoupTF , PPAR and RevErb ). Despite the variability of NR expression in immune cells, these results suggest that some of the NR may be co-regulated in human immune cells