Interrogation of the Limitations and Capabilities of the Model-Gel-Tissue Assay and Application to Soft Tissue Modulus Evaluation

Abstract

The correlation between changes in mechanical properties and the onset of disease has led to an increased interest in assessing the elastic modulus of soft tissues as a biomarker for disease progression. In addition, soft tissue mechanical properties are desired for biomechanical modeling for surgical procedure planning and intraoperative guidance. Unfortunately, soft tissue modulus evaluation has proven inherently difficult due to tissue consistency and shape, and the approaches are highly variant. The work presented in this thesis focuses on the development, application, and interrogation of a novel soft tissue mechanical property evaluation technique, termed the Model-Gel-Tissue (MGT) assay, which utilizes a combination of a gel embedding process, direct mechanical testing, and computational modeling to analyze the elastic properties of a soft tissue sample. The goal was to develop a repeatable and adaptable evaluation technique that also allowed for irregularly shaped specimens and standardization of the implementation. This was accomplished by a rapid-embedding of the tissue in a gel with surfaces of known and uniform shape. The mechanical testing output is then utilized in a finite element model of the system developed from computed tomography (CT) scans of the specimen, in order to evaluate the mechanical properties of the embedded tissue. Preliminary testing of the MGT assay was implemented using fibrotic murine livers to assess the capability of the technique relative to traditional indentation testing. The assay was then used to investigate the correlation between microstructural collagen content and macroscopic tissue modulus in a murine model of breast cancer. Subsequently, the assay was used to investigate the propensity of modulus as an indicator of treatment resistance in a second murine model of breast cancer. Finally, extensive sensitivity tests were performed to qualify the fidelity of the system. The results of this work show that modulus assessment via the MGT assay correlates to traditional testing, as well as to tissue collagen content, and the concatenation of the work indicates that the MGT assay serves as a reliable and adaptable soft tissue modulus evaluation system.