The quantification of mechanical properties of soft tissues has been of great interest for more than two decades because they have the potential of being used as biomarkers for disease diagnosis. Indentation techniques, the most recognized techniques for characterizing mechanical properties, are widely used for basic science investigations in research labs. The use of elastography techniques coupled with imaging technologies has been growing rapidly in recent years, which is promising for clinical applications. Each technique produces different mechanical behaviors due to the interaction of the stimuli and the structure of the tissue.An appropriate model will parameterize these behaviors to reflect the corresponding tissue microscopic features with high fidelity. The objective of this thesis is to identify combinations of techniques and models that will yield mechanical parameters with diagnostic interpretations about tissue microenvironment.Three techniques for characterizing tissue viscoelastic properties were developed and validated, each offers strengths in a large variety of applications. Indentation based techniques measure low-frequency force-displacement curves under different loading profiles. Ultrasound-based techniques and optical based techniques measure the dispersion behaviors of the propagating wave velocities at mid-to-high frequency ranges. When a material is linear, isotropic, and contains only elastic components, the “intrinsic” elastic modulus of the material can be obtained independently of the technique used when corrections are properly made to eliminate the bias from boundary effects. If the material includes time-dependent components, models must be included in the analysis to provide parametric estimates. Classical models for viscoelastic solids such as the Kelvin-Voigt model do not fully represent mechanical measurements in tissues because they are not material continua. Tissue properties are determined in part by fluid movement in the open- and closed-cell compartments found within a viscoelastic collagen matrix that is actively maintained by the embedded cells to meet programmed needs. These biphasic (solid/fluid) media exhibit multifaceted deformation responses that are particularly difficult to model using a concise feature set.The Kelvin-Voigt fractional derivative (KVFD) model introduced in this study represents the measurement data of a broad range in both time and frequency domain with a small number of parameters, and it yields stable estimates for many types of phantoms and tissues. It is superior to the integer derivative models for the materials and techniques we used in this study. Moreover, the KVFD model provides a three-dimensional feature space of mechanical properties that properly characterizes the composition and structure of a material. This was validated through measurements on gelatin-cream emulsion samples exhibiting viscoelastic behavior, as well as ex vivo liver tissue samples. For the elastic property, KVFD parameter E_0 mainly represents the elasticity of the solid matrix and is approximately equal to the shear modulus no matter which technique is used. For the viscous property, when combined with different measurement techniques, KVFD model parameter α and τ represent different tissue components. The combination of these techniques and the KVFD model have the potential to be able to distinguish between healthy and pathological tissues described by the histological features.
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Soft tissue viscoelastic properties: measurements, models and interpretation