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

Naila Rahman,Kathy Xu,Corey A Baron,Matthew D Budde,Arthur Brown,Mohammad Omer,Niels Bergsland

doi:10.1371/journal.pone.0255711

Naila Rahman, Kathy Xu + Show 5 more

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https://doi.org/10.1371/journal.pone.0255711

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Abstract

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. 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. Bland-Altman plots showed negligible biases between test and retest sessions. ROI-based CVs revealed high reproducibility for most metrics (CVs < 15%). Voxel-wise CV maps revealed high reproducibility for μA (CVs ~ 10%), but low reproducibility for OGSE metrics (CVs ~ 50%). 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 (> 6%), respectively.

Highlights

Diffusion MRI provides a non-invasive means to capture microstructure changes in the brain during development, aging, disease, and injury by probing the diffusion of water molecules [1]
Most of the μA diffusion MRI (dMRI) metrics are reproducible in both ROI-based and voxel-wise analysis, while the Oscillating gradient spin echo (OGSE) dMRI metrics are only reproducible in ROI-based analysis
diffusion tensor imaging (DTI) assumes the dMRI signal is entirely characterized by Gaussian diffusion [2] and utilizes a diffusion tensor model to estimate metrics such as mean diffusivity (MD) and fractional anisotropy (FA)

Summary

Introduction

Diffusion MRI (dMRI) provides a non-invasive means to capture microstructure changes in the brain during development, aging, disease, and injury by probing the diffusion of water molecules [1]. DKI provides more information about the underlying tissue via the diffusion kurtosis, which quantifies the deviation from Gaussian diffusion [3] Both DTI and DKI are unable to distinguish between microstructural changes and neuron fiber orientation dispersion [2, 4], reducing their specificity to microstructural changes in brain regions with crossing fibers. 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

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