C01 Multiscale mechanical properties of tumors and tumor environment – from tissue specimens to patients

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More than 80% of hepatocellular carcinomas (HCC) are found in fibrotic or cirrhotic livers, suggesting that liver fibrosis creates a premalignant environment for tumor development. However, little is known about the causes of the differential aggressiveness of HCC in different parenchymal environments. During hepatocarcinogenesis, multiple mechanisms and distinct cytogenetic pathways collectively upregulate growth factor signaling and are closely associated with changes in mechanical properties, which can be detected by MRE. Like HCC, pancreatic ductal adeno-carcinoma (PDAC) is often diagnosed at advanced stages with the liver as the main site of metastases. During tumor progression, PDAC and HCC cells undergo epithelial-mesenchymal transition, which can be triggered and promoted by altering the mechanical properties of the tumor stroma. The objective here is to use in vivo multiparametric quantitative MRI (qMRI), tomoelastography and multiscale-multifrequency MRE (mMRE) for investigating the coevolution of tumor and niche from a physics perspective. To this end, we plan to develop tools for automated texture analysis to reveal the mechanical heterogeneity of in vivo tissue based on stiffness and fluidity maps. Together with ex vivo multiparametric qMRI/mMRE, clinical serum markers, and histopathology, we aim to identify the mechanical signature of malignant tumor niches in the liver and pancreas. We hypothesize that the development of hepato-pancreatic tumors in vivo is critically influenced by the mechanical interactions between tumor and microenvironment. Biophysical and biomechanical imaging parameters including viscoelastic dispersion, mechanical heterogeneity, and solid stress can help identify the biomechanical traits that predict tumor aggressiveness, malignant transformation, and response to therapy. The goal of this sub-project is to develop novel imaging markers that can detect spatial heterogeneity in the mechanical properties of tumor/niche tissues and evaluate how stiffness dispersion, heterogeneity, and tissue fluidity change with the progression of HCC, liver metastases, and PDAC. We will create a library of the biophysical and biomechanical hallmarks of hepatic and pancreatic tumors in patients and surgically resected tissue samples across tissue length scales. To create a roadmap of predictive tumor imaging markers, we will compile a database of tumor biophysical properties and clinical parameters in collaboration with C03 and the coordination project. C01 is a key component of our research unit, acquiring clinical imaging data of hepato-pancreatic tumors for analysis of mechanical heterogeneity, dispersion (C02), and solid stress (C03), and providing tissues for various analyses including micromechanical studies of tumor-matrix interactions (A01), jamming/unjamming analyses (A03), metabolic profiling (A02), and decellularization/recellularization of hepatic and pancreatic tumors (B03).