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.

Enhanced and robust contrast in CEST MRI: Saturation pulse shape design via optimal control.

PURPOSE: To employ optimal control for the numerical design of Chemical Exchange Saturation Transfer (CEST) saturation pulses to maximize contrast and stability against B 0 $$ {\mathrm{B}}_0 $$ inhomogeneities. THEORY AND METHODS: We applied an optimal control framework for the design pulse shapes for CEST saturation pulse trains. The cost functional minimized both the pulse energy and the discrepancy between the corresponding CEST spectrum and the target spectrum based on a continuous radiofrequency (RF) pulse. The optimization is subject to hardware limitations. In measurements on a 7 T preclinical scanner, the optimal control pulses were compared to continuous-wave and Gaussian saturation methods. We conducted a comparison of the optimal control pulses with Gaussian, block pulse trains, and adiabatic spin-lock pulses. RESULTS: The optimal control pulse train demonstrated saturation levels comparable to continuous-wave saturation and surpassed Gaussian saturation by up to 50 % in phantom measurements. In phantom measurements at 3 T the optimized pulses not only showcased the highest CEST contrast, but also the highest stability against field inhomogeneities. In contrast, block pulse saturation resulted in severe artifacts. Dynamic Bloch-McConnell simulations were employed to identify the source of these artifacts, and underscore the B 0 $$ {\mathrm{B}}_0 $$ robustness of the optimized pulses. CONCLUSION: In this work, it was shown that a substantial improvement in pulsed saturation CEST imaging can be achieved by using Optimal Control design principles. It is possible to overcome the sensitivity of saturation to B0 inhomogeneities while achieving CEST contrast close to continuous wave saturation.

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.