The localization regime in a nutshell.

High diffusion-sensitizing magnetic field gradients have been more and more often applied nowadays to achieve a better characterization of the microstructure. As the resulting spin-echo signal significantly deviates from the conventional Gaussian form, various models have been employed to interpret these deviations and to relate them with the microstructural properties of a sample. In this paper, we argue that the non-Gaussian behavior of the signal is a generic universal feature of the Bloch-Torrey equation. We provide a simple yet rigorous description of the localization regime emerging at high extended gradients and identify its origin as a symmetry breaking at the reflecting boundary. We compare the consequent non-Gaussian signal decay to other diffusion NMR regimes such as slow-diffusion, motional-narrowing and diffusion-diffraction regimes. We emphasize limitations of conventional perturbative techniques and advocate for non-perturbative approaches which may pave a way to new imaging modalities in this field.

Localization regime in diffusion NMR: Theory and experiments.

In this work we investigate the emergence of the localization regime for diffusion NMR in various geometries: inside slabs, inside cylinders and outside rods arranged on a square array. At high gradients, the transverse magnetization is strongly attenuated in the bulk, whereas the macroscopic signal is formed by the remaining magnetization localized near boundaries of the sample. As a consequence, the signal is particularly sensitive to the microstructure. The theoretical analysis relies on recent mathematical advances on the study of the Bloch-Torrey equation. Experiments were conducted with hyperpolarized xenon-129 gas in 3D-printed phantoms and show an excellent agreement with numerical simulations and theoretical predictions. Our mathematical arguments and experimental evidence indicate that the localization regime with a stretched-exponential decay of the macroscopic signal is a generic feature of diffusion NMR that can be observed at moderately high gradients in most NMR scanners.

Probing Surface-to-Volume Ratio of an Anisotropic Medium by Diffusion NMR with General Gradient Encoding.

Since the seminal paper by Mitra et al., diffusion MR has been widely used in order to estimate surface-to-volume ratios. In this paper, we generalize Mitra's formula for arbitrary diffusion encoding waveforms, including recently developed q-space trajectory encoding sequences. We show that the surface-to-volume ratio can be significantly misestimated using the original Mitra's formula without taking into account the applied gradient profile. In order to obtain more accurate estimation in anisotropic samples, we propose an efficient and robust optimization algorithm to design diffusion gradient waveforms with prescribed features. Our results are supported by Monte Carlo simulations.

Diffusion-limited reactions in dynamic heterogeneous media.

Most biochemical reactions in living cells rely on diffusive search for target molecules or regions in a heterogeneous overcrowded cytoplasmic medium. Rapid rearrangements of the medium constantly change the effective diffusivity felt locally by a diffusing particle and thus impact the distribution of the first-passage time to a reaction event. Here, we investigate the effect of these dynamic spatiotemporal heterogeneities onto diffusion-limited reactions. We describe a general mathematical framework to translate many results for ordinary homogeneous Brownian motion to heterogeneous diffusion. In particular, we derive the probability density of the first-passage time to a reaction event and show how the dynamic disorder broadens the distribution and increases the likelihood of both short and long trajectories to reactive targets. While the disorder slows down reaction kinetics on average, its dynamic character is beneficial for a faster search and realization of an individual reaction event triggered by a single molecule.

The Kärger vs bi-exponential model: Theoretical insights and experimental validations.

We revise three common models accounting for water exchange in pulsed-gradient spin-echo measurements: a bi-exponential model with time-dependent water fractions, the Kärger model, and a modified Kärger model designed for restricted diffusion, e.g. inside cells. The three models are compared and applied to experimental data from yeast cell suspensions. The Kärger model and the modified Kärger model yield very close results and accurately fit the data. The bi-exponential model, although less rigorous, has a natural physical interpretation and suggests a new experimental modality to estimate the water exchange time.