Keywords: Simulation/Validation, Microstructure, simulations, validation

Motivation: The non-monotonic dependence of the diffusion kurtosis on diffusion time has been observed in tissue, yet its relation to membrane integrity and tissue geometry remains unknown.

Goal(s): We investigate the relation between the characteristic time  t_peak and the tissue parameters, such as cell size, volume fraction and permeability.

Approach: We perform Monte Carlo simulations of diffusion and exchange in randomly, densely packed spheres with varying permeability, cell fractions and sizes, and identify the value of t_peak.

Results: We obtain an empirical, albeit highly accurate relation of t_peak to tissue parameters in a broad parameter range.

Impact: Diffusion-kurtosis time-dependence is sensitive to pathological changes in membrane integrity and cellular structure in diseases, such as ischemic stroke and tumors. Numerical simulations suggest an empirical interpretation of kurtosis time-dependence, offering a novel biomarker for in vivo evaluation of pathology.

Keywords: Microstructure, Microstructure, brain, diffusion, microstructure, metabolites, DW-MRS, spines, gray matter, simulation

Motivation: Dendritic spines are fine microstructures increase the complexity of brain cells. Spines are characteristic morphological feature of neurons and their density can change with pathological conditions.

Goal(s): Quantification of dendritic spines in gray matter in human brain using diffusion-weighted MR spectroscopy

Approach: Using Monte-Carlo diffusion simulations for metabolites, to investigate how a dMRS signal is sensitive to the dendritic spines.

Results: Our findings suggests potential biomarkers for characterizing dendritic spines in human brain gray matter using diffusion-weighted MR spectroscopy

Impact: This work establishes a benchmark for spine sensitivity and quantification. Also it offers potential dMRS acquisition parameters for spine detection in human brain.   

Keywords: DWI/DTI/DKI, Microstructure, Kurtosis, OGSE, PGSE, Frequency dependence, Time dependence, Human brain

Motivation: Investigation of the time- and frequency-dependence of diffusion kurtosis, a valuable probe of microstructure and exchange, is becoming feasible in humans due to advances of gradient hardware.

Goal(s): To provide more data regarding time- and frequency-dependent diffusion kurtosis in the human brain.

Approach: Diffusion MRI with pulsed and oscillating gradients (PGSE/OGSE) at different but partially overlapping diffusion times using a head gradient insert and spiral readouts.

Results: Biphasic kurtosis behavior (i.e., increase with time in the short-time range and decrease with time in the long-time range covered by OGSE/PGSE, respectively) was observed, with an explainable mismatch between both sequences in the overlapping range.

Impact: Studying the time- and frequency-dependence of diffusion kurtosis using both PGSE and OGSE experiments over a range of diffusion times and length scales can provide valuable information about brain tissue complexity, heterogeneity, and inter-compartmental water exchange.

Keywords: Diffusion Acquisition, Diffusion/other diffusion imaging techniques, Exchange

Motivation: Exchange is an important effect in diffusion MR of the brain but remains difficult to quantify using conventional methods and signal models due to parameter degeneracy. 

Goal(s): To develop and demonstrate robust measurement of exchange in the mouse brain.

Approach: A method based on double diffusion encoding was previously developed to probe exchange isolated from other effects, yielding robust exchange time measurements. We apply this method in vivo for the first time.

Results: We report a fast in vivo exchange time of approximately 38 ms as compared to 146 ms in a fixed sample, obtained by averaging through a slice. 

Impact: Cellular water exchange reflects not only structural characteristics but has also been linked to metabolism. Quantifying exchange may yield rich information, yet methods to do so are not mature. Here, we demonstrate a unique, isolated measurement of exchange in vivo.

Keywords: Microstructure, Microstructure

Motivation: The investigation of extracellular spaces with diffusion weighted MRI andMRS is limited by the ubiquitous distribution and fast exchange of water, while endogenous metabolites are mostly intracellular.

Goal(s): Investigate the diffusion characteristics of ingested MSM compared to water and endogenous metabolites.

Approach: Multi b-valued single and double diffusion encoded MRS in humans at 3T.

Results: MSM diffuses anisotropically, but considerably faster than intracellular metabolites, and exhibits a substantially different behavior compared to both water and metabolites.

Impact: MSM provides a novel probe of extracellular spaces similar to water but with differences that could be rotted in different transmembrane exchange properties.

Keywords: Microstructure, Diffusion/other diffusion imaging techniques, Diffusion modeling, Quantitative imaging, Tissue characterization

Motivation: This study assesses the Neurite Exchange Imaging (NEXI) microstructure model in human cortex using clinical MRI data, addressing the model's clinical applicability.

Goal(s): How meaningful, robust, and reproducible are microstructural properties in the human cortex estimated using the NEXI diffusion model on clinical data?

Approach: Scan-rescan clinical data from six volunteers were collected and processed. NEXI was estimated and compared to expected cortical distributions and to the myelin water fraction distribution.

Results: NEXI provided robust, biologically plausible results and maintained inter-subject sensitivity and intra-subject reproducibility. A significant correlation between exchange time and myelin water fraction supports the relationship between membrane permeability and myelination.

Impact: We successfully estimate the Neurite Exchange Imaging (NEXI) model on clinical MRI data and report a strong correlation between the estimated exchange time, a proxy for membrane permeability, and the Myelin Water Fraction in the human cortex.

Keywords: Microstructure, Microstructure, Gray Matter, Exchange, Double Diffusion Encoding

Motivation: SMEX is a model of diffusion which may enable gray matter (GM) microstructural mapping in-vivo. However, clinical translation necessitates reliable parameter estimation with short scan time and limited gradient strength.

Goal(s): Resolve degeneracies for SMEX parameter estimation and enable more accurate and precise GM microstructural mapping

Approach: We complement the Single Diffusion Encoding measurement with Double Diffusion Encoding. We analyze the signal theoretically for low b-values in terms of the cumulant expansion, and for high b-values with numerical simulations.

Results: Planar diffusion encoding resolves an intrinsic degeneracy in SMEX at low b, and generally provides higher accuracy and precision in model parameter estimation.

Impact: The improvement in parameter estimation afforded by tensor encoded diffusion may enable shorter sequences and lower gradient strengths, thereby facilitating clinical translation of SMEX.

Keywords: Microstructure, Aging, Hippocampus; High-field MRI

Motivation: The hippocampus serves multiple cognitive functions, yet little is known about its microstructural development.

Goal(s): To leverage recent MRI hardware and microstructure modeling advances to capture hippocampal cell-body (soma) and projection (neurite) development during late-childhood and adolescence.

Approach: Diffusion MRI data was acquired in 88 participants aged 8-18 years using a 3T Connectom scanner (with 300mT/m gradients), and analyzed using the Soma and Neurite Density Imaging model.

Results: For the first time, we identified distinct developmental patterns of hippocampal microstructural subcomponents. Specifically, we found an age-related increase in neurite fraction and concurrent decrease in extracellular fraction and soma radius.

Impact: We report, for the first time, distinct neurite and soma developmental profiles in the hippocampus during late childhood/adolescence. This forms a crucial baseline for understanding developmental disorders, and opens new avenues for corroborating in vivo diffusion with histology.

Keywords: Microstructure, Spinal Cord, Spinal cord; soma; microstructure; modeling; diffusion

Motivation: Multicompartment models of diffusion MRI have proven valuable in the brain. 

Goal(s): However, application of these models in the spinal cord (SC) remains relatively understudied. 

Approach: Here, we address challenges related to acquisition and image processing in order to apply the Soma and Neurite Density Imaging (SANDI) model in the human SC in 11 healthy subjects. 

Results: We show that SANDI captures differences between white and gray matter tissue types and across the functionally relevant white matter pathways and gray matter architectures and has the potential to act as a biomarker for biomedical applications. 

Impact: We show that the Soma and Neurite Density Imaging (SANDI) diffusion model is a feasible method to characterize both white and gray matter tissue microstructure of the in vivo human spinal cord on clinical scanners.