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Elastographic Imaging of Pancreatic Cancer Tumor Microenvironment

Hexuan Wang

Supervised by Professor Marvin Doyley

Goergen Hall 108 Eisenberg Room

Pancreatic ductal adenocarcinoma (PDAC) is a common and aggressive malignancy with a 5-year survival rate of less than 5%. Surgical resection with targeted neoadjuvant therapy remains the most effective treatment plan available. Despite extensive research, targeted therapies have made minimally incremental improvement in efficacy for PDAC patients. The unique abnormal PDAC tumor microenvironment has been postulated to promote tumor growth and inhibit drug delivery. The role of the dense stroma con- tents and high interstitial pressure are under active investigation regarding their role in vascular compression.

An imaging technique that can measure the tumor stroma stiffness would provide crucial information on how the tumor microenvironment changes during different therapies. Contrast agent-based computed tomography, and magnetic resonance imaging modalities are faced with contrast pooling and poor contrast delivery, also a result of the abnormal tumor microenvironment. The objective of this thesis is to establish shear modulus as a surrogate biomarker for tissue pressure in pancreatic cancer tumors using ultrasound elastography including model-based iterative reconstruction schemes and shear wave elasticity imaging. To achieve this goal, the following objectives are to be satisfied: (1) establish the relationship between shear modulus and stromal components of the pancreatic cancer tumor microenvironment; (2) investigate how shear modulus impacts drug delivery and vascular patency in pancreatic cancer tumors; (3) assess the effects of radiotherapy and immunotherapy on shear modulus and the underlying tissue components.

The results of these studies showed that the shear modulus is an excellent surrogate imaging biomarker for tissue pressure in pancreatic cancer tumors. We demonstrated through three animal studies that shear modulus is inversely related to drug delivery in pancreatic adenocarcinoma tumors. Shear modulus also changes in response to modifications in tumor stroma attributes due to emerging treatment regimens such as immunotherapy and stereotactic body radiation therapy.