Vascular regional analysis unveils differential responses to anti-angiogenic therapy in pancreatic xenografts through macroscopic photoacoustic imaging

Abstract

Pancreatic cancer (PC) is a highly lethal malignancy and the third leading cause of cancer deaths in the U.S. Despite major innovations in imaging technologies, there are limited surrogate radiographic indicators to aid in therapy planning and monitoring. Amongst the various imaging techniques Ultrasound-guided photoacoustic imaging (US-PAI) is a promising modality based on endogenous blood (hemoglobin) and blood oxygen saturation (StO2) contrast to monitor response to anti-angiogenic therapies. Adaptation of US-PAI to the clinical realm requires macroscopic configurations for adequate depth visualization, illuminating the need for surrogate radiographic markers, including the tumoral microvessel density (MVD). In this work, subcutaneous xenografts with PC cell lines AsPC-1 and MIA-PaCa-2 were used to investigate the effects of receptor tyrosine kinase inhibitor (sunitinib) treatment on MVD and StO2. Through histological correlation, we have shown that regions of high and low vascular density (HVD and LVD) can be identified through frequency domain filtering of macroscopic PA images which could not be garnered from purely global analysis. We utilized vascular regional analysis (VRA) of treatment-induced StO2and total hemoglobin (HbT) changes. VRA as a tool to monitor treatment response allowed us to identify potential timepoints of vascular remodeling, highlighting its ability to provide insights into the TME not only for sunitinib treatment but also other anti-angiogenic therapies.