Error quantification in multi-parameter mapping facilitates robust estimation and enhanced group level sensitivity

Multi-Parameter Mapping (MPM) is a comprehensive quantitative neuroimaging protocol that enables estimation of four physical parameters (longitudinal and effective transverse relaxation rates R1 and R2*, proton density PD, and magnetization transfer saturation MTsat) that are sensitive to microstructural tissue properties such as iron and myelin content. Their capability to reveal microstructural brain differences, however, is tightly bound to controlling random noise and artefacts (e.g. caused by head motion) in the signal. Here, we introduced a method to estimate the local error of PD, R1, and MTsat maps that captures both noise and artefacts on a routine basis without requiring additional data. To investigate the method's sensitivity to random noise, we calculated the model-based signal-to-noise ratio (mSNR) and showed in measurements and simulations that it correlated linearly with an experimental raw-image-based SNR map. We found that the mSNR varied with MPM protocols, magnetic field strength (3T vs. 7T) and MPM parameters: it halved from PD to R1 and decreased from PD to MT_sat by a factor of 3-4. Exploring the artefact-sensitivity of the error maps, we generated robust MPM parameters using two successive acquisitions of each contrast and the acquisition-specific errors to down-weight erroneous regions. The resulting robust MPM parameters showed reduced variability at the group level as compared to their single-repeat or averaged counterparts. The error and mSNR maps may better inform power-calculations by accounting for local data quality variations across measurements. Code to compute the mSNR maps and robustly combined MPM maps is available in the open-source hMRI toolbox.

Temperature relaxation in strongly-coupled binary ionic mixtures

New facilities such as the National Ignition Facility and the Linac Coherent Light Source have pushed the frontiers of high energy-density matter. These facilities offer unprecedented opportunities for exploring extreme states of matter, ranging from cryogenic solid-state systems to hot, dense plasmas, with applications to inertial-confinement fusion and astrophysics. However, significant gaps in our understanding of material properties in these rapidly evolving systems still persist. In particular, non-equilibrium transport properties of strongly-coupled Coulomb systems remain an open question. Here, we study ion-ion temperature relaxation in a binary mixture, exploiting a recently-developed dual-species ultracold neutral plasma. We compare measured relaxation rates with atomistic simulations and a range of popular theories. Our work validates the assumptions and capabilities of the simulations and invalidates theoretical models in this regime. This work illustrates an approach for precision determinations of detailed material properties in Coulomb mixtures across a wide range of conditions.

Development and Validation of Fluorinated Amino Acid Parameters for use with the AMBER ff15ipq Protein Force Field

We developed force field parameters for fluorinated aromatic amino acids enabling molecular dynamics (MD) simulations of fluorinated proteins. These parameters are tailored to the AMBER ff15ipq protein force field and enable the modeling of 4, 5, 6, and 7F-tryptophan, 3F- and 3,5F-tyrosine, and 4F- or 4-CF3-phenylalanine. The parameters include 181 unique atomic charges derived using the Implicitly Polarized Charge (IPolQ) scheme in the presence of SPC/Eb explicit water molecules and 9 unique bond, angle, or torsion terms. Our simulations of benchmark peptides and proteins maintain expected conformational propensities on the μs-timescale. In addition, we have developed an open-source Python program to calculate fluorine relaxation rates from MD simulations. The extracted relaxation rates from protein simulations are in good agreement with experimental values determined by 19F NMR. Collectively, our results illustrate the power and robustness of the IPolQ lineage of force fields for modeling structure and dynamics of fluorine containing proteins at the atomic level.

Massively Multidimensional Diffusion-Relaxation Correlation MRI

Diverse approaches such as oscillating gradients, tensor-valued encoding, and diffusion-relaxation correlation have been used to study microstructure and heterogeneity in healthy and pathological biological tissues. Recently, acquisition schemes with free gradient waveforms exploring both the frequency-dependent and tensorial aspects of the encoding spectrum b(ω) have enabled estimation of nonparametric distributions of frequency-dependent diffusion tensors. These “D(ω)-distributions” allow investigation of restricted diffusion for each distinct component resolved in the diffusion tensor trace, anisotropy, and orientation dimensions. Likewise, multidimensional methods combining longitudinal and transverse relaxation rates, R1 and R2, with (ω-independent) D-distributions capitalize on the component resolution offered by the diffusion dimensions to investigate subtle differences in relaxation properties of sub-voxel water populations in the living human brain, for instance nerve fiber bundles with different orientations. By measurements on an ex vivo rat brain, we here demonstrate a “massively multidimensional” diffusion-relaxation correlation protocol joining all the approaches mentioned above. Images acquired as a function of the magnitude, normalized anisotropy, orientation, and frequency content of b(ω), as well as the repetition time and echo time, yield nonparametric D(ω)-R1-R2-distributions via a Monte Carlo data inversion algorithm. The obtained per-voxel distributions are converted to parameter maps commonly associated with conventional lower-dimensional methods as well as unique statistical descriptors reporting on the correlations between restriction, anisotropy, and relaxation.

NMR Relaxivities of Paramagnetic Lanthanide-Containing Polyoxometalates

The current trend for ultra-high-field magnetic resonance imaging (MRI) technologies opens up new routes in clinical diagnostic imaging as well as in material imaging applications. MRI selectivity is further improved by using contrast agents (CAs), which enhance the image contrast and improve specificity by the paramagnetic relaxation enhancement (PRE) mechanism. Generally, the efficacy of a CA at a given magnetic field is measured by its longitudinal and transverse relaxivities r1 and r2, i.e., the longitudinal and transverse relaxation rates T1−1 and T2−1 normalized to CA concentration. However, even though basic NMR sensitivity and resolution become better in stronger fields, r1 of classic CA generally decreases, which often causes a reduction of the image contrast. In this regard, there is a growing interest in the development of new contrast agents that would be suitable to work at higher magnetic fields. One of the strategies to increase imaging contrast at high magnetic field is to inspect other paramagnetic ions than the commonly used Gd(III)-based CAs. For lanthanides, the magnetic moment can be higher than that of the isotropic Gd(III) ion. In addition, the symmetry of electronic ground state influences the PRE properties of a compound apart from diverse correlation times. In this work, PRE of water 1H has been investigated over a wide range of magnetic fields for aqueous solutions of the lanthanide containing polyoxometalates [DyIII(H2O)4GeW11O39]5– (Dy-W11), [ErIII(H2O)3GeW11O39]5– (Er-W11) and [{ErIII(H2O)(CH3COO)(P2W17O61)}2]16− (Er2-W34) over a wide range of frequencies from 20 MHz to 1.4 GHz. Their relaxivities r1 and r2 increase with increasing applied fields. These results indicate that the three chosen POM systems are potential candidates for contrast agents, especially at high magnetic fields.

A new type of non-Hermitian phase transition in open systems far from thermal equilibrium

We demonstrate a new type of non-Hermitian phase transition in open systems far from thermal equilibrium, which can have place in the absence of an exceptional point. This transition takes place in coupled systems interacting with reservoirs at different temperatures. We show that the spectrum of energy flow through the system caused by the temperature gradient is determined by the $$\varphi^{4}$$ φ 4 -potential. Meanwhile, the frequency of the maximum in the spectrum plays the role of the order parameter. The phase transition manifests itself in the frequency splitting of the spectrum of energy flow at a critical point, the value of which is determined by the relaxation rates and the coupling strength. Near the critical point, fluctuations of the order parameter diverge according to a power law with the critical exponent that depends only on the ratio of reservoirs temperatures. The phase transition at the critical point has the non-equilibrium nature and leads to the change in the energy flow between the reservoirs. Our results pave the way to manipulate the heat energy transfer in the coupled out-of-equilibrium systems.

Cardiac myocyte intrinsic contractility and calcium handling deficits underlie heart organ dysfunction in murine cancer cachexia

Cachexia is a muscle wasting syndrome occurring in many advanced cancer patients. Cachexia significantly increases cancer morbidity and mortality. Cardiac atrophy and contractility deficits have been observed in patients and in animal models with cancer cachexia, which may contribute to cachexia pathophysiology. However, underlying contributors to decreased in vivo cardiac contractility are not well understood. In this study, we sought to distinguish heart-intrinsic changes from systemic factors contributing to cachexia-associated cardiac dysfunction. We hypothesized that isolated heart and cardiac myocyte functional deficits underlie in vivo contractile dysfunction. To test this hypothesis, isolated heart and cardiac myocyte function was measured in the colon-26 adenocarcinoma murine model of cachexia. Ex vivo perfused hearts from cachectic animals exhibited marked contraction and relaxation deficits during basal and pacing conditions. Isolated myocytes displayed significantly decreased peak contraction and relaxation rates, which was accompanied by decreased peak calcium and decay rates. This study uncovers significant organ and cellular-level functional deficits in cachectic hearts outside of the catabolic in vivo environment, which is explained in part by impaired calcium cycling. These data provide insight into physiological mechanisms of cardiomyopathy in cachexia, which is critical for the ultimate development of effective treatments for patients.

Quantification of H217O by 1H-MR imaging at 3 T: a feasibility study

Background Indirect 1H-magnetic resonance (MR) imaging of 17O-labelled water allows imaging in vivo dynamic changes in water compartmentalisation. Our aim was to describe the feasibility of indirect 1H-MR methods to evaluate the effect of H217O on the MR relaxation rates by using conventional a 3-T equipment and voxel-wise relaxation rates. Methods MR images were used to calculate the R1, R2, and R2* relaxation rates in phantoms (19 vials with different H217O concentrations, ranging from 0.039 to 5.5%). Afterwards, an experimental animal pilot study (8 rats) was designed to evaluate the in vivo relative R2 brain dynamic changes related to the intravenous administration of 17O-labelled water in rats. Results There were no significant changes on the R1 and R2* values from phantoms. The R2 obtained with the turbo spin-echo T2-weighted sequence with 20-ms echo time interval had the higher statistical difference (0.67 s−1, interquartile range 0.34, p < 0.001) and Spearman correlation (rho 0.79). The R2 increase was adjusted to a linear fit between 0.25 and 5.5%, represented with equation R2 = 0.405 concentration + 0.3215. The highest significant differences were obtained for the higher concentrations (3.1–5.5%). The rat brain MR experiment showed a mean 10% change in the R2 value after the H217O injection with progressive normalisation. Conclusions Indirect 1H-MR imaging method is able to measure H217O concentration by using R2 values and conventional 3-T MR equipment. Normalised R2 relative dynamic changes after the intravenous injection of a H217O saline solution provide a unique opportunity to map water pathophysiology in vivo, opening the analysis of aquaporins status and modifications by disease at clinically available 3-T proton MR scanners.

Dynamically Tunable Plasmon-induced Transparency in Parallel Black Phosphorus Nanoribbons

In this paper, we investigate the dynamically tunable plasmon-induced transparency (PIT) effects in parallel black phosphorus nanoribbons (BPNRs). The results show that the BPNRs having different lengths can be regarded as bright modes. Single-band, double-band, triple-band, and multi-band PIT effects based on the bright-bright mode coupling between parallel BPNRs are achieved. The physical mechanism of the single-band model can be explained theoretically by the radiating two-oscillator (RTO) model. Due to the heavier effective mass in the zigzag (ZZ) direction of the BP, the frequencies of the transparent peaks are shifted to lower frequencies when the placement directions of BPNRs are changed from the X-direction to the Y-direction. Furthermore, the resonant frequencies of the transparent windows in each model can be tuned by changing the relaxation rates of the BPNRs. The frequencies of the transparent windows are blue-shifted as the relaxation rates are increased. Finally, The corresponding sensors based on single-band PIT effect show high sensitivities of 7.35 THz/RIU. Our study has potential applications for improving the design of multiple-band filters, sensors and on-off switcher.

Analysis of conformational exchange processes using methyl-TROSY-based Hahn echo measurements of quadruple-quantum relaxation

Transverse nuclear spin relaxation is a sensitive probe of chemical exchange on timescales on the order of microseconds to milliseconds. Here we present an experiment for the simultaneous measurement of the relaxation rates of two quadruple-quantum transitions in 13CH3-labelled methyl groups. These coherences are protected against relaxation by intra-methyl dipolar interactions and so have unexpectedly long lifetimes within perdeuterated biomacromolecules. However, these coherences also have an order of magnitude higher sensitivity to chemical exchange broadening than lower order coherences and therefore provide ideal probes of dynamic processes. We show that analysis of the static magnetic field dependence of zero-, double- and quadruple-quantum Hahn echo relaxation rates provides a robust indication of chemical exchange and can determine the signed relative magnitudes of proton and carbon chemical shift differences between ground and excited states. We also demonstrate that this analysis can be combined with established Carr–Purcell–Meiboom–Gill (CPMG) relaxation dispersion measurements, providing improved precision in parameter estimates, particularly in the determination of 1H chemical shift differences.