A new nonlinear parameter in the developed strain-to-applied strain of the soft tissues and its application in ultrasound elasticity imaging

Strain developed under quasi-static deformation has been mostly used in ultrasound elasticity imaging (UEI) to determine the stiffness change of tissues. However, the strain measure in UEI is often less sensitive to a subtle change of stiffness. This is particularly true for Crohn's disease where we have applied strain imaging to the differentiation of acutely inflamed bowel from chronically fibrotic bowel. In this study, a new nonlinear elastic parameter of the soft tissues is proposed to overcome this limit. The purpose of this study is to evaluate the newly proposed method and demonstrate its feasibility in the UEI. A nonlinear characteristic of soft tissues over a relatively large dynamic range of strain was investigated. A simplified tissue model based on a finite element (FE) analysis was integrated with a laboratory developed ultrasound radio-frequency (RF) signal synthesis program. Two-dimensional speckle tracking was applied to this model to simulate the nonlinear behavior of the strain developed in a target inclusion over the applied average strain to the surrounding tissues. A nonlinear empirical equation was formulated and optimized to best match the developed strain-to-applied strain relation obtained from the FE simulation. The proposed nonlinear equation was applied to in vivo measurements and nonlinear parameters were further empirically optimized. For an animal model, acute and chronic inflammatory bowel disease was induced in Lewis rats with trinitrobenzene sulfonic acid (TNBS)-ethanol treatments. After UEI, histopathology and direct mechanical measurements were performed on the excised tissues. The extracted nonlinear parameter from the developed strain-to-applied strain relation differentiated the three different tissue types with 1.96 ± 0.12 for normal, 1.50 ± 0.09 for the acutely inflamed and 1.03 ± 0.08 for the chronically fibrotic tissue. T-tests determined that the nonlinear parameters between normal, acutely inflamed and fibrotic tissue types were statistically significantly different (normal/ fibrotic [p = 0.0000185], normal/acutely inflamed [p = 0.0013] and fibrotic/acutely inflamed [p = 0.0029]). This technique may provide a sensitive and robust tool to assess subtle stiffness changes in tissues such as in acutely inflamed bowel wall.