There is currently no reliable method for early characterization of breast cancer response to neoadjuvant chemotherapy (NAC) [1,2]. Given that disruption of normal structural architecture occurs in cancer-bearing tissue, we hypothesize that further structural changes occur in response to NAC. Consequently, we are investigating the use of modalityindependent elastography (MIE) [3-8] as a method for monitoring mechanical integrity to predict long term outcomes in NAC. Recently, we have utilized a Demons non-rigid image registration method that allows 3D elasticity reconstruction in abnormal tissue geometries, making it particularly amenable to the evaluation of breast cancer mechanical properties. While past work has reflected relative elasticity contrast ratios , this study improves upon that work by utilizing a known stiffness reference material within the reconstruction framework such that a stiffness map becomes an absolute measure. To test, a polyvinyl alcohol (PVA) cryogel phantom and a silicone rubber mock mouse tumor phantom were constructed with varying mechanical stiffness. Results showed that an absolute measure of stiffness could be obtained based on a reference value. This reference technique demonstrates the ability to generate accurate measurements of absolute stiffness to characterize response to NAC. These results support that ‘referenced MIE' has the potential to reliably differentiate absolute tumor stiffness with significant contrast from that of surrounding tissue. The use of referenced MIE to obtain absolute quantification of biomarkers is also translatable across length scales such that the characterization method is mechanics-consistent at the small animal and human application.
Clinical observations have long suggested that cancer progression is accompanied by extracellular matrix remodeling and concomitant increases in mechanical stiffness. Due to the strong association of mechanics and tumor progression, there has been considerable interest in incorporating methodologies to diagnose cancer through the use of mechanical stiffness imaging biomarkers, resulting in commercially available US and MR elastography products. Extension of this approach towards monitoring longitudinal changes in mechanical properties along a course of cancer therapy may provide means for assessing early response to therapy; therefore a systematic study of the elasticity biomarker in characterizing cancer for therapeutic monitoring is needed. The elastography method we employ, modality independent elastography (MIE), can be described as a model-based inverse image-analysis method that reconstructs elasticity images using two acquired image volumes in a pre/post state of compression. In this work, we present preliminary data towards validation and reproducibility assessment of our elasticity biomarker in a pre-clinical model of breast cancer. The goal of this study is to determine the accuracy and reproducibility of MIE and therefore the magnitude of changes required to determine statistical differences during therapy. Our preliminary results suggest that the MIE method can accurately and robustly assess mechanical properties in a pre-clinical system and provide considerable enthusiasm for the extension of this technique towards monitoring therapy-induced changes to breast cancer tissue architecture.