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NMR diffusion pore imaging: Experimental phase detection by double diffusion encoding

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 Publication date 2021
  fields Physics
and research's language is English




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Diffusion pore imaging is an extension of diffusion-weighted nuclear magnetic resonance imaging enabling the direct measurement of the shape of arbitrarily formed, closed pores by probing diffusion restrictions using the motion of spin-bearing particles. Examples of such pores comprise cells in biological tissue or oil containing cavities in porous rocks. All pores contained in the measurement volume contribute to one reconstructed image, which reduces the problem of vanishing signal at increasing resolution present in conventional magnetic resonance imaging. It has been previously experimentally demonstrated that pore imaging using a combination of a long and a narrow magnetic field gradient pulse is feasible. In this work, an experimental verification is presented showing that pores can be imaged using short gradient pulses only. Experiments were carried out using hyperpolarized xenon gas in well-defined pores. The phase required for pore image reconstruction was retrieved from double diffusion encoded (DDE) measurements, while the magnitude could either be obtained from DDE signals or classical diffusion measurements with single encoding. The occurring image artifacts caused by restrictions of the gradient system, insufficient diffusion time, and by the phase reconstruction approach were investigated. Employing short gradient pulses only is advantageous compared to the initial long-narrow approach due to a more flexible sequence design when omitting the long gradient and due to faster convergence to the diffusion long-time limit, which may enable application to larger pores.



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In porous material research, one main interest of nuclear magnetic resonance (NMR) diffusion experiments is the determination of the exact shape of pores. It has been a longstanding ques-tion if this is achievable in principle. In this work, we present a method using short diffusion gradient pulses only, which is able to reveal the shape of arbitrary closed pores without rely-ing on a priori knowledge. In comparison to former approaches, the method has reduced de-mands on relaxation times and allows for a more flexible NMR sequence design, since, for example, stimulated echoes can be used.
Nuclear magnetic resonance (NMR) diffusion measurements are widely used to derive parameters indirectly related to the microstructure of biological tissues and porous media. However, a direct imaging of cell or pore shapes and sizes would be of high interest. For a long time, determining pore shapes by NMR diffusion acquisitions seemed impossible, because the necessary phase information could not be preserved. Here we demonstrate experimentally using the measurement technique which we have recently proposed theoretically that the shape of arbitrary closed pores can be imaged by diffusion acquisitions, which yield the phase information. For this purpose, we use hyperpolarized xenon gas in well-defined geometries. The signal can be collected from the whole sample which mainly eliminates the problem of vanishing signal at increasing resolution of conventional NMR imaging. This could be used to non-invasively gain structural information inaccessible so far such as pore or cell shapes, cell density or axon integrity.
224 - Kerstin Demberg 2021
This paper presents a novel approach on solving the phase problem in nuclear magnetic resonance (NMR) diffusion pore imaging, a method, which allows imaging the shape of arbitrary closed pores filled with an NMR-detectable medium for investigation of the microstructure of biological tissue and porous materials. Classical q-space imaging composed of two short diffusion-encoding gradient pulses yields, analogously to diffraction experiments, the modulus squared of the Fourier transform of the pore image which entails an inversion problem: An unambiguous reconstruction of the pore image requires both magnitude and phase. Here, the phase information is recovered from the Fourier modulus by applying a phase retrieval algorithm. This allows omitting experimentally challenging phase measurements using specialized temporal gradient profiles. A combination of the hybrid input-output algorithm and the error reduction algorithm was used with dynamically adapting support (shrinkwrap extension). No a priori knowledge on the pore shape was fed to the algorithm except for a finite pore extent. The phase retrieval approach proved successful for simulated data with and without noise and was validated in phantom experiments with well-defined pores using hyperpolarized xenon gas.
Double diffusion encoding (DDE) magnetic resonance measurements of the water signal offers a unique ability to separate the effect of microscopic anisotropic diffusion in structural units of tissue from the overall macroscopic orientational distribution of cells. However, the specificity in detected microscopic anisotropy is limited as the signal is averaged over different cell types and across tissue compartments. Performing side-by-side metabolite DDE spectroscopy (DDES) and water DDES in which a wide range of b-values is used to gradually eliminate the extracellular contribution provides complementary measures from which intracellular and extracellular microscopic fractional anisotropies ($mu$FA) and diffusivities can be estimated. Metabolites are largely confined to the intracellular space and therefore provide a benchmark for intracellular diffusivity of specific cell types. Here, we aimed to estimate tissue- and compartment-specific human brain microstructure by combining water and metabolites DDES experiments. We performed DDES in human subjects in two brain regions that contain widely different amounts of white matter (WM) and gray matter (GM): parietal white matter (PWM) and occipital gray matter (OGM) on a 7 T MRI scanner. Results of the metabolite DDES experiments in both PWM and OGM suggest a highly anisotropic intracellular space within neurons and glia, with the possible exception of gray matter glia. Tortuosity values in the cytoplasm for water and tNAA, obtained with correlation analysis of microscopic parallel diffusivity with respect to GM/WM tissue fraction in the volume of interest, are remarkably similar for both molecules, while exhibiting a clear difference between gray and white matter, suggesting a more crowded cytoplasm and more complex cytomorphology of neuronal cell bodies and dendrites in GM than those found in long-range axons in WM.
Purpose: Biophysical tissue models are increasingly used in the interpretation of diffusion MRI (dMRI) data, with the potential to provide specific biomarkers of brain microstructural changes. However, the general Standard Model has recently shown that model parameter estimation from dMRI data is ill-posed unless very strong magnetic gradients are used. We analyse this issue for the Neurite Orientation Dispersion and Density Imaging with Diffusivity Assessment (NODDIDA) model and demonstrate that its extension from Single Diffusion Encoding (SDE) to Double Diffusion Encoding (DDE) solves the ill-posedness and increases the accuracy of the parameter estimation. Methods: We analyse theoretically the cumulant expansion up to fourth order in b of SDE and DDE signals. Additionally, we perform in silico experiments to compare SDE and DDE capabilities under similar noise conditions. Results: We prove analytically that DDE provides invariant information non-accessible from SDE, which makes the NODDIDA parameter estimation injective. The in silico experiments show that DDE reduces the bias and mean square error of the estimation along the whole feasible region of 5D model parameter space. Conclusions: DDE adds additional information for estimating the model parameters, unexplored by SDE, which is enough to solve the degeneracy in the NODDIDA model parameter estimation.
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