INNOvations in elastography to quantify Viscosity and ANisotropy of muscle – INNOVAN

Ultrasound (US) shear wave elastography (SWE) has become popular in both basic and clinical sciences to measure the localized mechanical properties of biological tissues non-invasively. As such, SWE demonstrated potential for diagnosis of various pathologies in which tissue stiffness is altered (e.g., breast cancer, liver fibrosis). SWE is also widely used to assess muscle stiffness in health and disease. However, for anisotropic, viscous and stiff tissues such as muscles, SWE suffers from two main drawbacks that limit its application. First, 2D SWE measurements are not sufficient to describe the 3D behavior of the muscle and are not able to account for muscle anisotropy due to fibers. This is a major limitation because the muscle fibers move in the 3D space, inducing a bias on 2D muscle SWE measurements. Second, while viscosity is a crucial property for the muscle, current SWE technologies cannot provide viscosity measurements. Therefore the first aim of the INNOVAN project is to tackle these two main drawbacks, in order to strongly extend the potential of SWE. First, a motorized probe and a technique for tilting the propagation of the shear wave will be developed in order to characterize the muscle in 3D (task 2). Second, a newly designed US sequence that account for diffraction effects will allow measurement of the shear wave attenuation (task 3). Therefore, both tasks will enable to measure the conservation and loss moduli in 3D, leading to a full characterization of muscle rheological properties (final product 1). This will be confirmed by using MR-Elastography as a comparison method (task. 4). The second aim of this project if to use the final product 1 to provide a better fundamental understanding of the 3D muscle mechanical behavior (task 5). We will determine the best rheological model depending on the space direction, the stretching level and the contraction level. In addition we hypothesize that the muscle tension level would increase both elastic and viscous anisotropy of muscle (hypothesis 1). Finally, we will construct a model to correct SWE measurements when the shear wave does not propagate along the muscle fiber direction (final product 2). This is crucial because measurements performed on pennate muscles, the vast majority of muscles, using commercialized SWE techniques are biased due to the inability to align the shear wave propagation with the muscle fiber direction. The third aim is to use the final product 1 for two clinical applications. The task 6 aims to determine: 1) whether muscle viscosity affects the amount of muscle injury induced by a strenuous exercise and 2) whether the changes in muscle structure associated with muscle injury can be quantified from anisotropy measurements. We hypothesize (hypothesis 2) that 1) muscles with higher viscosity would have less damage, thanks to more energy dissipation during the eccentric exercise; and 2) muscle anisotropy would be affected due to the muscle damage and would be correlated to the changes in functional impairments. Muscle anisotropy and viscosity measurements could therefore be relevant indicators of muscle injury and the possible susceptibility of muscle weakness. The task 7 aims to determine: 1) how muscle 3D viscoelastic properties are affected in children with Duchene muscular Dystrophy (DMD) and 2) whether changes in muscle 3D viscoelastic properties correlate with alteration in function at 1 year. We hypothesize that anisotropy and viscosity are dramatically altered in DMD muscles (hypothesis 3), leading to a simple non-invasive method to follow-up muscle function changes induced by DMD. Therefore the ambition of the multidisciplinary INNOVAN project is to propose innovations in US imaging in order to 1) obtain a better fundamental understanding of muscle behavior and 2) perform important clinical applications. For that purpose, we have brought together a consortium of leading research groups in physics, biomechanics, physiology and medicine.