Using double pulsed-field gradient MRI to study tissue microstructure in traumatic brain injury (TBI).

Double pulsed-field gradient (dPFG) MRI is proposed as a new sensitive tool to detect and characterize tissue microstructure following diffuse axonal injury. In this study dPFG MRI was used to estimate apparent mean axon diameter in a diffuse axonal injury animal model and in healthy fixed mouse brain. Histological analysis was used to verify the presence of the injury detected by MRI.

Microscopic diffusion anisotropy in the human brain: reproducibility, normal values, and comparison with the fractional anisotropy.

Human neuroimaging of tissue microstructure, such as axonal density and integrity, is key in clinical and neuroscience research. Most studies rely on diffusion tensor imaging (DTI) and the measures derived from it, most prominently fractional anisotropy (FA). However, FA also depends on fiber orientation distribution, a more macroscopic tissue property. Recently introduced measures of so-called microscopic diffusion anisotropy, diffusion anisotropy on a cellular or microscopic level, overcome this limitation because they are independent of the orientation distributions of axons and fibers. In this study, we evaluate the feasibility of two measures of microscopic diffusion anisotropy I(MA) and MA indices, for human neuroscience and clinical research. Both indices reflect the eccentricity of the cells but while I(MA) also depends on the cell size, MA is independent of the cell size and, like FA, scaled between 0 and 1. In whole-brain measurements of a group of 19 healthy volunteers, we measured average values and variability, evaluated their reproducibility, both within and between sessions, and compared MA to FA values in selected regions-of-interest (ROIs). The within- and between-session comparison did not show substantial differences but the reproducibility was much better for the MA than I(MA) (coefficient of variation between sessions 10.5% vs. 28.9%). The reproducibility was less for MA than FA overall, but comparable in the defined ROIs and the average group sizes required for between-group comparisons was similar (about 60 participants for a relative difference of 5%). Group-averaged values of MA index were generally larger and showed less variation across white-matter brain ROIs than FA (mean ± standard deviation of seven ROIs 0.83 ± 0.10 vs. 0.58 ± 0.13). Even in some gray-matter ROIs, MA values comparable to those of white matter ROIs were observed. Furthermore, the within-group variation of the values in white matter ROIs was lower for the MA compared to the FA (mean standard deviation over volunteers 0.038 vs. 0.049) which could be due to significant variability in the distribution of fiber orientation contributing to FA. These results indicate that MA (i) should be preferred to I(MA), (ii) has a reproducibility and group-size requirements comparable to those of FA; (iii) is less sensitive to the fiber orientation distribution than FA; and (iv) could be more sensitive to differences or changes of the tissue microstructure than FA. R1.1.

Mapping measures of microscopic diffusion anisotropy in human brain white matter in vivo with double-wave-vector diffusion-weighted imaging.

PURPOSE: To demonstrate that rotationally invariant measures of the diffusion anisotropy on a microscopic scale can be mapped in human brain white matter in vivo. METHODS: Echo-planar imaging experiments (resolution 3.0 × 3.0 × 3.0 mm(3) ) involving two diffusion-weighting periods (δ = 22 ms, Δ = 25 ms) in the same acquisition, so-called double-wave-vector or double-pulsed-field-gradient diffusion-weighting experiments, were performed on a 3 T whole-body magnetic resonance system with a long mixing time ( τm=45 ms) between the two diffusion weightings. RESULTS: The disturbing influences of background gradient fields, eddy currents, and the finite mixing time can be minimized using 84 direction combinations based on nine directions and their antipodes. In healthy volunteers, measures of the microscopic diffusion anisotropy ( IMA and MA indexes) could be mapped in white matter across the human brain. The measures were independent (i) of the absolute orientation of the head and of the diffusion directions and (ii) of the predominant fiber orientation. Compared to the fractional anisotropy derived from the conventional diffusion tensor, the double-wave-vector indexes exhibit a narrower distribution, which could reflect their independence of the fiber orientation distribution. CONCLUSIONS: Mapping measures of the microscopic diffusion anisotropy in human brain white matter is feasible in vivo and could help to characterize tissue microstructure in the healthy and pathological brain.

Microstructural information from angular double-pulsed-field-gradient NMR: From model systems to nerves.

PURPOSE: To evaluate the ability of angular double-pulsed-field gradient (d-PFG) MR to provide microstructural information in complex phantoms and fixed nerves. METHODS: We modeled the signal in angular d-PFG MR experiments performed on phantoms of increasing complexity where the ground truth is known a priori. After analyzing the microstructural features of such phantoms the same methodology was used to study microstructural features in fixed nerves. RESULTS: We found that our modeling is able to determine with high accuracy and with very little prior knowledge the sizes and relative fractions of the restricted components as well as the fraction of the free diffusing water molecules. The same approach was used to study nerve microstructure. We found the apparent averaged axonal diameter (AAD) to be 2.3 ± 0.2 µm. However, here the results depended, to some extent, on the parameters used to collect the data and were affected by the diffusion time. CONCLUSION: Modeling of the angular d-PFG MR signal provides a means to obtain accurate microstructural information in complex phantoms where the ground truth is known. This approach also seems to be suitable for obtaining microstructural features in fixed nerves. Magn Reson Med 74:25-32, 2015. © 2014 Wiley Periodicals, Inc.

Anisotropic phantom to calibrate high-q diffusion MRI methods.

A silicon oil-filled glass capillary array is proposed as an anisotropic diffusion MRI phantom. Together with a computational/theoretical pipeline these provide a gold standard for calibrating and validating high-q diffusion MRI experiments. The phantom was used to test high angular resolution diffusion imaging (HARDI) and double pulsed-field gradient (d-PFG) MRI acquisition schemes. MRI-based predictions of microcapillary diameter using both acquisition schemes were compared with results from optical microscopy. This phantom design can be used for quality control and quality assurance purposes and for testing and validating proposed microstructure imaging experiments and the processing pipelines used to analyze them.

Two-dimensional diffusion time correlation experiment using a single direction gradient.

The time dependence of the diffusion coefficient is a well known property of porous media and commonly obtained by pulsed field gradient (PFG) NMR. In practical materials, its analysis can be complicated by the presence of a broad pore size distribution and multiple fluid phases with different diffusion coefficients. We propose a two-dimensional Diffusion Time Correlation experiment (DTC), which utilizes the double-PFG with a single-direction gradient to yield a two-dimensional correlation function of the diffusion coefficient for two different diffusion times. This correlation map separates out restricted diffusion from the bulk diffusion process and we demonstrate this on a plant and bulk water sample. In its development, we show that the d-PFG should then be thought of as correlating two apparent diffusion coefficients measured by two overlapping gradient waveforms.