Noninvasive assessment of muscle mechanics using biomedical ultrasound and acoustoelasticity theory : from simulation to phantom fabrication and in vivo studies

Abstract

Depending on their types, muscles govern locomotion, heat generation, cardiac function, peristalsis, or vasoconstriction. To improve life quality or assist clinical diagnosis, muscle conditions can be assessed from the perspective of mechanics. Despite being the gold standard, conventional mechanical tests (e.g., uniaxial tensile test) measure muscle mechanical properties destructively. However, ex vivo and in vivo muscle mechanical properties differ essentially. It is thus imperative to evaluate muscles in a completely noninvasive and in vivo way. The collective advantages of biomedical ultrasound imaging (e.g., real-time, non-ionizing radiation, and cost-effectiveness) render it an appealing tool of choice. Muscle microstructures (e.g., cellular level) result in complex macro mechanical properties (e.g., nonlinearity, anisotropy). This necessitates realistic theoretical models to link muscle’s composite microstructures and its macro mechanical properties for informative interpretation. Ultrasound imaging methods that can dictate muscle nonlinear and anisotropic properties comprehensively are also indispensable, but controllable muscle-mimicking phantoms as experimental ground truth for validation are lacking. This thesis therefore tackles the aforementioned challenges by 1) building a new theoretical model using the acoustoelasticity theory for the mathematical description of muscle mechanics; 2) developing an ultrasound imaging method that combines shear wave imaging (SWI) and strain imaging (SI) as a noninvasive assessment tool; 3) using finite element (FE) simulations and 3D-printed hydrogel phantoms for quantitative validation of the developed ultrasound imaging method; and 4) proposing a new fabrication method of ultrasound vessel-mimicking phantoms (VMPs) for smooth muscle evaluation. Specifically, • for skeletal muscle evaluation, a theoretical model was first established to link shear wave speed, material deformation, and material parameters (MPs) based on 1) a composite constitutive model which macroscopically exhibits hyperelasticity and transversely isotropy and 2) the acoustoelasticity theory in validation with FE simulations. Combining SWI and SI, an ultrasound imaging sequence was conducted on in vivo passive human biceps brachii muscles. Fitting the experimental data with the theoretical equations, muscle microstructure-related MPs, including myofiber stiffness, stiffness ratio of myofiber to extracellular matrix (ECM), and ECM volume ratio, were estimated and agreed well with the literature. Using FE models and 3D-printed hydrogel phantoms, the theoretical model was validated quantitatively. The in silico and in vitro MPs agreed well with the ground truth, thus confirming the accuracy of the theoretical model incorporated with SWI for muscle assessment. • For smooth muscle evaluation, customized VMPs with complicated lumen geometries were fabricated using 3D printing with a water-soluble polyvinyl alcohol (PVA) filament. B-mode imaging and power Doppler imaging (PDI) were conducted on VMPs to confirm good phantom fabrication quality. Flow velocities from ultrasound-based ultrafast Doppler (uDoppler) imaging and shear wave speeds from SWI agreed well with the simulation results. The fabrication method is foreseen to facilitate the development of ultrasound imaging techniques for blood vessels. Regarded as a preliminary but a fundamental step towards comprehensive muscle assessment using biomedical ultrasound, this thesis provides theoretical, computational, and experimental frameworks for noninvasive assessment of muscle mechanics, especially for in vivo skeletal muscles.