Characterization and correction of time-varying eddy currents for diffusion MRI

Purpose: To develop and test a method for reducing artifacts due to time-varying eddy currents in oscillating gradient spin-echo (OGSE) diffusion images. Methods: An in-house algorithm (TVEDDY), that for the first time retrospectively models eddy current decay, was tested on pulsed gradient spin echo and OGSE brain images acquired at 7 T. Image pairs were acquired using opposite polarity diffusion gradients. A three-parameter exponential decay model (two amplitudes and a time constant) was used to characterize and correct eddy current distortions by minimizing the intensity difference between image pairs. Correction performance was compared with conventional correction methods by evaluating the mean squared error (MSE) between diffusion-weighted images acquired with opposite polarity diffusion gradients. As a ground-truth comparison, images were corrected using field dynamics up to third order in space, measured using a field monitoring system. Results: Time-varying eddy currents were observed for OGSE, which introduced blurring that was not reduced using the traditional approach but was diminished considerably with TVEDDY and field monitoring–informed model-based reconstruction. No MSE difference was observed between the conventional approach and TVEDDY for pulsed gradient spin echo, but for OGSE TVEDDY resulted in significantly lower MSE than the conventional approach. The field-monitoring reconstruction had the lowest MSE for both pulsed gradient spin echo and OGSE. Conclusion: This work establishes that it is possible to estimate time-varying eddy currents from the actual diffusion data, which provides substantial image-quality improvements for gradient-intensive diffusion MRI acquisitions like OGSE

Diffusion dispersion imaging: Mapping oscillating gradient spin-echo frequency dependence in the human brain.

PURPOSE: Oscillating gradient spin-echo (OGSE) diffusion MRI provides information about the microstructure of biological tissues by means of the frequency dependence of the apparent diffusion coefficient (ADC). ADC dependence on OGSE frequency has been explored in numerous rodent studies, but applications in the human brain have been limited and have suffered from low contrast between different frequencies, long scan times, and a limited exploration of the nature of the ADC dependence on frequency. THEORY AND METHODS: Multiple frequency OGSE acquisitions were acquired in healthy subjects at 7T to explore the power-law frequency dependence of ADC, the diffusion dispersion. Furthermore, a method for optimizing the estimation of the ADC difference between different OGSE frequencies was developed, which enabled the design of a highly efficient protocol for mapping diffusion dispersion. RESULTS: For the first time, evidence of a linear dependence of ADC on the square root of frequency in healthy human white matter was obtained. Using the optimized protocol, high-quality, full-brain maps of apparent diffusion dispersion rate were also demonstrated at an isotropic resolution of 2 mm in a scan time of 6 min. CONCLUSIONS: This work sheds light on the nature of diffusion dispersion in the healthy human brain and introduces full-brain diffusion dispersion mapping at clinically relevant scan times. These advances may lead to new biomarkers of pathology or improved microstructural modeling

Estimation of free water-corrected microscopic fractional anisotropy.

Water diffusion anisotropy MRI is sensitive to microstructural changes in the brain that are hallmarks of various neurological conditions. However, conventional metrics like fractional anisotropy are confounded by neuron fiber orientation dispersion, and the relatively low resolution of diffusion-weighted MRI gives rise to significant free water partial volume effects in many brain regions that are adjacent to cerebrospinal fluid. Microscopic fractional anisotropy is a recent metric that can report water diffusion anisotropy independent of neuron fiber orientation dispersion but is still susceptible to free water contamination. In this paper, we present a free water elimination (FWE) technique to estimate microscopic fractional anisotropy and other related diffusion indices by implementing a signal representation in which the MRI signal within a voxel is assumed to come from two distinct sources: a tissue compartment and a free water compartment. A two-part algorithm is proposed to rapidly fit a set of diffusion-weighted MRI volumes containing both linear- and spherical-tensor encoding acquisitions to the representation. Simulations an

Test–Retest Reproducibility of In Vivo Magnetization Transfer Ratio and Saturation Index in Mice at 9.4 Tesla

Background: Magnetization transfer saturation (MTsat) imaging was developed to reduce T1 dependence and improve specificity to myelin, compared to the widely used MT ratio (MTR) approach, while maintaining a feasible scan time. As MTsat imaging is an emerging technique, the reproducibility of MTsat compared to MTR must be evaluated. Purpose: To assess the test–retest reproducibility of MTR and MTsat in the mouse brain at 9.4 T and calculate sample sizes potentially required to detect effect sizes ranging from 6% to 14%. Study Type: Prospective. Subjects: Twelve healthy C57Bl/6 mice. Field Strength/Sequence: 9.4 T; magnetization transfer imaging using FLASH-3D Gradient Echo; T2-weighted TurboRARE spin echo. Assessment: All mice were scanned at two timepoints (5 days apart). MTR and MTsat maps were analyzed using mean region-of-interest (ROIs: corpus callosum [CC], internal capsule [IC], hippocampus [HC], cortex [CX], and thalamus [TH]), and whole brain voxel-wise analysis. Statistical Tests: Bland–Altman plots were used to assess biases between test–retest measurements. Test–retest reproducibility was evaluated via between and within-subject coefficients of variation (bsCV and wsCV, respectively). Sample sizes required were calculated (significance level: 95%; power: 80%), given effect sizes ranging from 6% to 14%, using both between and within-subject approaches. Results were considered statistically significant at P ≤ 0.05. Results: Bland–Altman plots showed negligible biases between test–retest sessions (MTR: 0.0009; MTsat: 0). ROI-based and voxel-wise CVs revealed high reproducibility for both MTR (ROI-bsCV/wsCV: CC—4.5/2.8%; IC—6.1/5.2%; HC—5.7/4.6%; CX—5.1/2.3%; TH—7.4/4.9%) and MTsat (ROI-bsCV/wsCV: CC—6.3/4.8%; IC—7.3/5.1%; HC—9.5/6.4%; CX—6.7/6.5%; TH—7.2/5.3%). With a sample size of 6, changes on the order of 15% could be detected in MTR and MTsat, both between and within subjects, while smaller changes (6%–8%) required sample sizes of 10–15 for MTR, and 15–20 for MTsat. Data Conclusion: MTsat exhibited comparable reproducibility to MTR, while providing sensitivity to myelin with less T1 dependence than MTR. Evidence Level: 2. Technical Efficacy: Stage 1

Enabling Complex Fibre Geometries Using 3D Printed Axon-Mimetic Phantoms

Purpose: To introduce a method to create 3D-printed axon-mimetic phantoms with complex fibre orientations to characterise the performance of diffusion magnetic resonance imaging (MRI) models and representations in the presence of orientation dispersion. Methods: An extension to an open-source 3D printing package was created to produce a set of five 3D-printed axon-mimetic (3AM) phantoms with various combinations of bending and crossing fibre orientations. A two-shell diffusion MRI scan of the five phantoms in water was performed at 9.4T. Diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), the ball and stick model, neurite orientation density and dispersion imaging (NODDI), and Bingham-NODDI were all fit to the resulting diffusion MRI data. A ground truth map of that phantom’s crossing angles and/or arc radius was registered to the diffusion-weighted images. Metrics from each model and representation were compared to the ground-truth maps, and a quadratic regression model was fit to each combination of output metric and ground-truth metric. Results: The mean diffusivity (MD) metric defined by DTI was insensitive to crossing angle but increased with fibre curvature. Axial diffusivity (AD) decreased with increasing crossing angle. DKI’s diffusivity metrics replicated the trends seen in DTI, and its mean kurtosis (MK) metric decreased with fibre curvature, except in regions with high crossing angles. The estimated stick volume fraction in the ball and stick model decreased with increasing fibre curvature and crossing angle. NODDI’s intra-neurite volume fraction was insensitive to crossing angle, and its orientation dispersion index (ODI) was correlated to crossing angle. Bingham-NODDI’s intra-neurite volume fraction was also insensitive to crossing angle, while its primary ODI (ODIP) was also correlated to crossing angle and its secondary ODI (ODIS) was insensitive to crossing angle. For both NODDI models, the volume fractions of the extra-neurite and CSF compartments had low reliability with no clear relationship to crossing angle. Conclusion: Inexpensive 3D-printed axon-mimetic phantoms can be used to investigate the effect of fibre curvature and crossings on diffusion MRI representations and models of diffusion signal. The dependence of several representations and models on fibre dispersion/crossing was investigated. As expected, Bingham-NODDI was best able to characterise planar fibre dispersion in the phantoms

Test-retest reproducibility of in vivo oscillating gradient and microscopic anisotropy diffusion MRI in mice at 9.4 Tesla

Background and purpose Microstructure imaging with advanced diffusion MRI (dMRI) techniques have shown increased sensitivity and specificity to microstructural changes in various disease and injury models. Oscillating gradient spin echo (OGSE) dMRI, implemented by varying the oscillating gradient frequency, and microscopic anisotropy (μA) dMRI, implemented via tensor valued diffusion encoding, may provide additional insight by increasing sensitivity to smaller spatial scales and disentangling fiber orientation dispersion from true microstructural changes, respectively. The aims of this study were to characterize the test-retest reproducibility of in vivo OGSE and μA dMRI metrics in the mouse brain at 9.4 Tesla and provide estimates of required sample sizes for future investigations. Methods Twelve adult C57Bl/6 mice were scanned twice (5 days apart). Each imaging session consisted of multifrequency OGSE and μA dMRI protocols. Metrics investigated included μA, linear diffusion kurtosis, isotropic diffusion kurtosis, and the diffusion dispersion rate (Λ), which explores the power-law frequency dependence of mean diffusivity. The dMRI metric maps were analyzed with mean region-of-interest (ROI) and whole brain voxel-wise analysis. Bland-Altman plots and coefficients of variation (CV) were used to assess the reproducibility of OGSE and μA metrics. Furthermore, we estimated sample sizes required to detect a variety of effect sizes. Results Bland-Altman plots showed negligible biases between test and retest sessions. ROI-based CVs revealed high reproducibility for most metrics (CVs \u3c 15%). Voxel-wise CV maps revealed high reproducibility for μA (CVs ~ 10%), but low reproducibility for OGSE metrics (CVs ~ 50%). Conclusion Most of the μA dMRI metrics are reproducible in both ROI-based and voxel-wise analysis, while the OGSE dMRI metrics are only reproducible in ROI-based analysis. Given feasible sample sizes (10–15), μA metrics and OGSE metrics may provide sensitivity to subtle microstructural changes (4–8%) and moderate changes (\u3e 6%), respectively