Synopsis

Noninvasive measurement of mechanical properties of brain tissue using Magnetic Resonance Elastography has been a promising method for investigating neurological disorders such as multiple sclerosis, hydrocephalus and Alzheimer’s. However, due to regional and directional dependency of brain stiffness, estimating anisotropic stiffness is important. Previous studies have investigated anisotropic and isotropic stiffness separately but none of them investigated the two together. Objective of this study is to investigate both isotropic and anisotropic stiffness together and independently compare with age and with each other. Results demonstrated a significant decrease in isotropic and anisotropic stiffness with age in some regions of the brain.

Introduction

Methods

Brain MRE and Diffusion Tensor Imaging(DTI) was performed on 28 healthy subjects(n = 17 males, n = 11 females; mean age: 34.3 years, age range 18-62 years). A written informed consent was obtained from each subject after an IRB approval. All imaging was performed on a 3T MRI scanner(Tim Trio, Siemens Healthcare, Erlangen, Germany). Figure 1 shows shows the experimental setup with a pneumatic driver(Resoundant Inc, Rochester, MN). MRE and DTI scans were performed subsequently with the same resolution. FOV:320mmx320mm; slice-thickness=2.5mm;resolution:2.5x2.5x2.5mm³;matrix:128x128; scan time ~20minutes.

MRE: A GRE MRE sequence with imaging parameters: FA:16°; TR/TE: 25/20.7ms; motion encoding gradient:60Hz; phase offsets:4; slices:55-60; Masks of different brain regions were generated using SPM12 software(The FIL Methods group, UCL, UK). Curl processing was performed to remove longitudinal waves and directional filter was applied to remove reflected waves. Isotropic shear stiffness maps were generated using MRE-Lab software(Mayo Clinic, Rochester, MN, USA) using 3D Local Frequency Estimation(LFE) inversion algorithm.

DTI: A diffusion-weighted (DW) single shot spin-echo echo-planar imaging multi-slice sequence was used with imaging parameters: diffusion encoding directions=256; TR=6400ms; TE=87ms; b-value=1000s/mm²; averages=1. A spatial-spectral filter was applied to the first harmonic of MRE displacements using a spectral window(5x5x5) followed by Helmholtz decomposition to separate compressional and shear components. Principal frequency of the spatially-spectrally filtered first harmonic displacement data was computed[16]. Approximate wavenumbers in each direction was obtained followed by narrowband spatial spectral filters with window of +/- 20 rad/m. Stiffness tensor was solved using the following equation of motion:

C_ii (δ²u^j_k(n_l)/δ²x^j_k(n_l)) = ρω²u^j_k(n_l)

where, u(n_l) and x_l(l=1,2,3) represent the directionally filtered displacements and the differential parameters along the local axes (n₁,n₂,n₃) respectively. C₁₁, C₂₂, C₃₃ are the compressional components and C₄₄, C₅₅, C₆₆ are shear components parallel and perpendicular to the fibres.

Statistical analysis was performed using Spearman correlation method(SAS14, SAS Institute Inc, NC) and graphs were generated using Minitab 17(Minitab Inc, PA).

Results

Figure 2 shows the magnitude, snapshots of 4 phase offsets and corresponding stiffness map.

Figure 3 shows spearman correlation for isotropic stiffness versus age. Moderate negative correlation (r_s=-0.43) with a significant p=0.02 was found in thalamus. Other regions did not show any significant correlation.

Table 1 shows spearman correlation for anisotropic stiffness versus age. C₃₃ demonstrated a significant decrease with age in whole brain (r_s=-0.52; p=0.004), gray matter (r_s=-0.50; p=0.005) and white matter (r_s=-0.50; p=0.005). C₁₁, C₂₂, C₄₄, C₅₅ and C₆₆ demonstrated no significant trend with age.

Table 2 shows spearman correlation for anisotropic versus isotropic stiffness. C₃₃ showed moderate positive correlation with isotropic stiffness in corpus callosum(r_s=0.45; p=0.01) and gray matter(r_s=0.42; p=0.02). However, C₂₂ showed moderate negative correlation with isotropic stiffness in whole brain(r_s=-0.43; p=0.02) and gray matter(r_s=-0.42; p=0.02). C₁₁, C₄₄, C₅₅, and C₆₆ did not demonstrate any trend with isotropic stiffness.

Discussion

A decrease in brain isotropic stiffness with age was more evident in thalamus than corpus callosum, white matter, gray matter and whole brain and this trend agrees with previous studies[3, 4, 17]. On the other hand, a decrease in anisotropic stiffness component(C₃₃) was found in white matter, gray matter and whole brain with age. While comparing isotropic with anisotropic stiffness, there was a moderate positive correlation found in anisotropic component C₃₃ in corpus callosum and gray matter while a moderate negative correlation in anisotropic direction C₂₂ in whole brain and gray matter and C₆₆ in thalamus. This suggests that brain stiffness varies regionally, and is directional and age dependent.

Conclusion

Acknowledgements

NIH-NHLBI: R01HL124096

Mayo clinic (Dr. Richard Ehman for providing the pillow driver)

References

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