Ultrasonic Rotational 3D Shear Wave Elasticity Imaging of In Vivo Skeletal Muscle

Ultrasound shear wave elasticity imaging (SWEI) has the potential to fill a critical clinical gap by providing biomarkers of muscle health that are noninvasive, inexpensive, and quantitative, which could augment or replace the current limited clinical options. However, skeletal muscle does not obey the typical isotropic assumption of SWEI systems, and instead has different properties in directions parallel and perpendicular to the muscle fibers (commonly modeled as a transversely isotropic material), complicating muscle characterization. Studies using traditional 2D-SWEI systems in skeletal muscle have been challenged by a high degree of variability, an inability to consistently measure properties perpendicular to the muscle fibers, and a reliance on manual probe alignment to the fiber direction. This dissertation investigates the ability of a rotational 3D-SWEI system to mitigate these limitations and presents preliminary research to move rotational 3D-SWEI for in vivo skeletal muscle characterization towards clinical translation.

Chapter 3 demonstrates the ability of a 3D-SWEI system to reconstruct shear wave speed (SWS) values along and across the muscle fibers without any manual probe alignment in the vastus lateralis of 10 healthy volunteers. The study demonstrates that 3D-SWEI improves the repeatability of SWS measurements both along and across the muscle fibers compared to 2D-SWEI measurements. Additionally, SWS in both dominant and non-dominant legs is evaluated, and no significant difference in SWS due to leg dominance is found along or across the fibers.

Chapter 4 presents the development and optimization of an algorithm for the automatic processing of 3D-SWEI skeletal muscle data. The results of several automatic algorithm implementations are compared to the results obtained using manual processing in 130 in vivo 3D-SWEI datasets, with analysis metrics including the percent of valid acquisitions (non-gross-error), percent bias, and absolute percent error. The optimal algorithm choice for relaxed muscle is determined to be a fixed lateral range (2–18 mm) Radon Sum method with multiwave detection and a shear wave speed ellipse fitting in the plane of symmetry. Additional results and conclusions are presented that can guide algorithm optimization for other applications.

In Chapter 5, the 3D-SWEI system and automatic analysis methods are used to evaluate the change in muscle stiffness with passive stretch in 10 healthy volunteers. A BioDex system is used to change the knee flexion angle, modulating the passive stretch of the vastus lateralis. These data are fit to report values of potential biomarkers that capture the change in muscle stiffness along and across the fibers with changing knee flexion, and the median within-subject variability of these biomarkers is found to be <16%. Additionally, the performance of the SWEI system is found to be best at high passive stretch states. The amplitude of shear waves propagating in different directions relative to the muscle fibers is also evaluated. This analysis shows that shear wave signal amplitude is higher along the fibers than across the fibers, that the difference in signal amplitude between the directions increases with increasing stretch, and that the magnitude of the difference is not explained by on-axis push strength differences or differences seen in TI material Green’s function simulations with matched shear moduli.

Overall, this work illustrates use of 3D-SWEI for in vivo skeletal muscle characterization and addresses key questions in the implementation of this technology for clinical use, including the repeatability of the system, methods to automatically analyze data, and the effects of passive stretch and joint position on 3D-SWEI measurements. This research can inform and enable further studies exploring the clinical application and development of 3D-SWEI biomarkers for skeletal muscle health.