Viscoelasticity of subcortical gray matter structures

Abstract

Viscoelastic mechanical properties of the brain assessed with magnetic resonance elastography (MRE) are sensitive measures of microstructural tissue health in neurodegenerative conditions. Recent efforts have targeted measurements localized to specific neuroanatomical regions differentially affected in disease. In this work, we present a method for measuring the viscoelasticity in subcortical gray matter (SGM) structures, including the amygdala, hippocampus, caudate, putamen, pallidum, and thalamus. The method is based on incorporating high spatial resolution MRE imaging (1.6 mm isotropic voxels) with a mechanical inversion scheme designed to improve local measures in pre-defined regions (soft prior regularization [SPR]). We find that in 21 healthy, young volunteers SGM structures differ from each other in viscoelasticity, quantified as the shear stiffness and damping ratio, but also differ from the global viscoelasticity of the cerebrum. Through repeated examinations on a single volunteer, we estimate the uncertainty to be between 3 and 7% for each SGM measure. Furthermore, we demonstrate that the use of specific methodological considerations-higher spatial resolution and SPR-both decrease uncertainty and increase sensitivity of the SGM measures. The proposed method allows for reliable MRE measures of SGM viscoelasticity for future studies of neurodegenerative conditions. Hum Brain Mapp 37:4221-4233, 2016. © 2016 Wiley Periodicals, Inc.

Keywords: brain; elastography; gray matter; hippocampus; thalamus; viscoelasticity.

Figure 1

Overview of proposed method for measuring SGM viscoelasticity: (A) high‐resolution MRE imaging of complex, full vector displacement field in the brain; (B) segmentation of SGM structures from T ₁‐weighted image (amygdala, Am; hippocampus, Hc; caudate, Ca; putamen, Pu; pallidum, Pa; and thalamus, Th); (C) estimation of viscoelastic shear stiffness, μ, and damping ratio, ξ, from displacement data using NLI with SPR to promote local homogeneity in SGM structures defined by the registered segmentation masks, along with the corresponding high‐resolution, T ₂‐weighted anatomical image. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Overview of shear stiffness, μ, measurements at 50 Hz in the population: (A) distribution of properties of each SGM structure and the cerebrum (CB), with line indicating population mean; (B) mean properties of each structure in standard space; (C) chart indicating significant differences between structures found through post hoc paired t‐test (P < 0.05 after Holm–Bonferroni correction). [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Overview of damping ratio, ξ, measurements at 50 Hz in the population: (A) distribution of properties of each SGM structure and the cerebrum (CB), with line indicating population mean; (B) mean properties of each structure in standard space; (C) chart indicating significant difference between structures found through post hoc paired t‐test (P < 0.05 after Holm–Bonferroni correction). [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 4

Measured properties of each structure at 50 Hz for all subjects, sorted by the properties of the cerebrum: (A) μ and (B) ξ. Charts indicating significant relationships between structures found through post hoc linear correlations: (C) μ and (D) ξ; and (E‐F) the relationships using cerebrum properties as a control variable. Significance is determined at P < 0.05 after Holm–Bonferroni correction. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 5

The use of soft prior regularization (SPR) improves the SGM viscoelastic property measures, μ and ξ. (A) Coefficient of variation, CV, for each SGM property measured with and without SPR. Without SPR, the CV for each measure is much larger indicating greater measurement uncertainty. (B) Effect size (Cohen's d) of difference between SGM properties and those of the entire cerebrum (CB) as measured using SPR and without. For all measures, d is greater with SPR, demonstrating the improved measurement sensitivity. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 6

Lower spatial resolution increases measurement uncertainty and reduces sensitivity. Comparison of coefficient of variation, CV, and effect size, d, for (A) μ and (B) ξ measurements from data at 1.6 and 2.0 mm isotropic voxel size (arrows point from 1.6 to 2.0 mm for each structure). For all measures except Th μ, the use of the lower 2.0 mm resolution resulted in both higher CV and lower d, demonstrating the gains from using higher resolution imaging when investigating SGM structures. [Color figure can be viewed at http://wileyonlinelibrary.com]