Thesis (Ph. D.)--University of Rochester. Department of Electrical and Computer Engineering, 2019.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
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 contents 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 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 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 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