Healthy aging affects the local mechanical properties of the human brain tissue but their estimation remains a challenge, especially in strongly anisotropic white matter regions. This study merges previous MRE aging research involving high-resolution, full-coverage, and multi-excitation MRE imaging with the ability to estimate anisotropic shear moduli locally. We identified important anisotropic differences in the storage modulus in the corpus callosum, which help differentiate old from the young.
Using isotropic tissue models for inversion, prior MRE studies have shown that there is a general decrease of the human brain stiffness during normal aging [1-5]. A class of anisotropic inversion methods rely on directional filtering of the displacement fields in judiciously chosen regions of the brain, followed by direct extraction of certain components of the stiffness tensor, which are assumed uniform in the chosen regions [6,7]. Romano et al. [6] found that one of the shear moduli decreases in the corticospinal tract of amyotrophic lateral sclerosis patients in-vivo. Schmidt et al. [7] reported good agreement of the anisotropic moduli with shear tests in an ex-vivo study of the porcine corpus callosum. Here we report a novel iterative inversion scheme based on a transversely isotropic tissue model, and we apply it for the in-vivo study of the human corpus callosum. We incorporate the data obtained in multi-excitation MRE and diffusion tensor imaging (DTI) study of the brain [8,9] in an iterative scheme that allows the estimation of shear moduli parallel and perpendicular to the local axon direction, and then compare the regional average values between two cohorts of healthy young and old adults.
A previous study [9] generated anterior-posterior (AP) excitation MRE, and left-right (LR) excitation brain MRE data for four young (24-32 years old) and 4 older (55-76 years old) males. Using a 3D multislab, multishot spiral MRE sequence [10], 3D complex displacement field data was collected at 50 Hz with 2mm3 isotropic spatial resolution. The isotropic viscoelastic properties were estimated for both AP and LR data using nonlinear inversion (NLI). Additionally, matched field-of-view and resolution (relative to MRE) diffusion tensor imaging (DTI) and high-resolution anatomical MPRAGE at 0.9mm3 isotropic resolution (TR/TI/TE = 2000/900/2.2 ms) were acquired, to register the subjects to the MNI JHU white matter atlas. Fig. 1 presents the scheme introduced here, which is labeled as ITI, for “Inverse Transversely Isotropic”. Under ITI, we use both AP and LR data, in conjunction with DTI, to extract the shear moduli of the transversely isotropic model. Fig. 1(A), focuses on an ROI consisting of 18x18x18 voxels, centered on the body of the corpus callosum of each subject. Based on Eq. (1), strain tensors for AP and LR excitations are obtained from the 3D displacement fields, as measured by MRE on world coordinates. For each voxel the strain fields are transformed to the local coordinate system aligned with the principal fiber direction Fig. 1(B). The linear stress-strain relationship for a nearly-incompressible, transversely isotropic medium is given by Eq. (3). The shear moduli correspond to shear stiffness parallel (μ1) and transverse (μ2) to the principal fiber direction, both complex in the case of harmonic waves in viscoelastic materials. Here we take the ratio of E1 / E2 = 2.7 [11] and ν12 = 0.4999. ITI inversion involves the following steps: a weak form of the governing equation is derived by multiplying it with a judiciously chosen function F(r) and integrating over the voxel volume(Eq. (4)). The integral is discretized using a higher order spatial scheme, which results in a system of linear equations for the pair of complex moduli that is solved iteratively.
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