Improved quantification in CEST-MRI by joint spatial total generalized variation.

PURPOSE: In this work, the use of joint Total Generalized Variation (TGV) regularization to improve Multipool-Lorentzian fitting of chemical exchange saturation transfer (CEST) Spectra in terms of stability and parameter signal-to-noise ratio (SNR) was investigated. THEORY AND METHODS: The joint TGV term was integrated into the nonlinear parameter fitting problem. To increase convergence and weight the gradients, preconditioning using a voxel-wise singular value decomposition was applied to the problem, which was then solved using the iteratively regularized Gauss-Newton method combined with a Primal-Dual splitting algorithm. The TGV method was evaluated on simulated numerical phantoms, 3T phantom data and 7T in vivo data with respect to systematic errors and robustness. Three reference methods were also implemented: The standard nonlinear fitting, a method using a nonlocal-means filter for denoising and the pyramid scheme, which uses downsampled images to acquire accurate start values. RESULTS: The proposed regularized fitting method showed significantly improved robustness (compared to the reference methods). In testing, over a range of SNR values the TGV fit outperformed the other methods and showed accurate results even for large amounts of added noise. Parameter values found were closer or comparable to the ground truth. For in vivo datasets, the added regularization increased the parameter map SNR and prevented instabilities. CONCLUSION: The proposed fitting method using TGV regularization leads to improved results over a range of different data-sets and noise levels. Furthermore, it can be applied to all Z-spectrum data, with different amounts of pools, where the improved SNR and stability can increase diagnostic confidence.

Cellulose modified to host functionalities via facile cation exchange approach.

Properties of cellulose are typically functionalized by organic chemistry means. We progress an alternative facile way to functionalize cellulose by functional group counter-cation exchange. While ion-exchange is established for cellulose, it is far from exploited and understood beyond the most common cation, sodium. We build on our work that established the cation exchange for go-to alkali metal cations. We expand and further demonstrate the introduction of functional cations, namely, lanthanides. We show that cellulose nanocrystals (CNCs) carrying sulfate-half ester groups can acquire properties through the counter-cation exchange. Trivalent lanthanide cations europium (Eu3+), dysprosium (Dy3+) and gadolinium (Gd3+) were employed. The respective ions showed distinct differences in their ability of being coordinated by the sulfate groups; with Eu3+ fully saturating the sulfate groups while for Gd3+ and Dy3+, values of 82 and 41 % were determined by compositional analysis. CNCs functionalized with Eu3+ displayed red emission, those containing Dy3+ exhibited no optical functionality, while those with Gd3+ revealed significantly altered magnetic relaxation times. Using cation exchange to alter cellulose properties in various ways is a tremendous opportunity for modification of the abundant cellulose raw materials for a renewable future.

STIM1 and Orai1 regulate Ca2+ microdomains for activation of transcription.

Since calcium (Ca2+) regulates a large variety of cellular signaling processes in a cell's life, precise control of Ca2+ concentrations within the cell is essential. This enables the transduction of information via Ca2+ changes in a time-dependent and spatially defined manner. Here, we review molecular and functional aspects of how the store-operated Ca2+ channel Orai1 creates spatiotemporal Ca2+ microdomains. The architecture of this channel is unique, with a long helical pore and a six-fold symmetry. Energetic barriers within the Ca2+ channel pathway limit permeation to allow an extensive local Ca2+ increase in close proximity to the channel. The precise timing of the Orai1 channel function is controlled by direct binding to STIM proteins upon Ca2+ depletion in the endoplasmic reticulum. These induced Ca2+ microdomains are tailored to, and sufficient for, triggering long-term activation processes, such as transcription factor activation and subsequent gene regulation. We describe the principles of spatiotemporal activation of the transcription factor NFAT and compare its signaling characteristics to those of the autophagy regulating transcription factors, MITF and TFEB.