Abstract
Elastography has become widely used clinically for characterising changes in soft tissue mechanics that are associated with altered tissue structure and composition. However, some soft tissues, such as muscle, are not isotropic as is assumed in clinical elastography implementations. This limits the ability of these methods to capture changes in anisotropic tissues associated with disease. The objective of this study was to develop and validate a novel elastography reconstruction technique suitable for estimating the linear viscoelastic mechanical properties of transversely isotropic soft tissues. We derived a divergence-free formulation of the governing equations for acoustic wave propagation through a linearly transversely isotropic viscoelastic material, and transformed this into a weak form. This was then implemented into a finite element framework, enabling the analysis of wave input data and tissue structural fibre orientations, in this case based on diffusion tensor imaging. To validate the material constants obtained with this method, numerous in silico phantom experiments were run which encompassed a range of variations in wave input directions, material properties, fibre structure and noise. The method was also tested on ex vivo muscle and in vivo human volunteer calf muscles, and compared with a previous curl-based inversion method. The new method robustly extracted the transversely isotropic shear moduli (G⊥', G∥', G″) from the in silico phantom tests with minimal bias, including in the presence of experimentally realistic levels of noise in either fibre orientation or wave data. This new method performed better than the previous method in the presence of noise. Anisotropy estimates from the ex vivo muscle phantom agreed well with rheological tests. In vivo experiments on human calf muscles were able to detect increases in muscle shear moduli with passive muscle stretch. This new reconstruction method can be applied to quantify tissue mechanical properties of anisotropic soft tissues, such as muscle, in health and disease.
Highlights
Tissue mechanical properties have long been linked to tissue structure and function (Bayly et al, 2014; Geng et al, 2009; Llinares-Benadero and Borrell, 2019)
We have developed a novel finite element based anisotropic inversion method, and an analysis pipeline that utilises displacements measured from MR elastography (MRE) images along with fibre directions from diffusion tensor imaging (DTI) to calculate transversely isotropic linearly viscoelastic shear moduli
Using a combination of in silico tests and experimental data from ex vivo muscle tissue, we have demonstrated that the method accurately estimates the mechanical properties of anisotropic materials with minimal bias in the presence of typical levels of experimental noise in both displacement and fibre direction
Summary
Tissue mechanical properties have long been linked to tissue structure and function (Bayly et al, 2014; Geng et al, 2009; Llinares-Benadero and Borrell, 2019). Elastography relies on the knowledge that the speed and attenuation of small amplitude waves travelling through a medium are directly related to the mechanical properties of the material. Some ultrasound-based techniques use time-of-flight to estimate wave speed and elasticity, but newer ultrasound approaches and MR elastography most commonly use a sinusoidal steady-state vibration input that is imaged synchronously over the domain of interest. This timevarying displacement data is used to estimate tissue mechanical properties, typically quantified by the shear modulus. Motion-sensitive gradients are added to the imaging sequence such that the displacements are encoded in the phase images at several time points across each vibration cycle (Muthupillai et al, 1995; Sinkus et al, 2000)
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