Pancreatic cancer is a disease with an incredibly poor survival rate. As only about 20% of patients are eligible for surgical resection, neoadjuvant treatments that can relieve symptoms and shrink tumors for surgical resection become critical. Many forms of treatments rely on increased vulnerability of cancerous cells, but tumors or regions within the tumors that may be hypoxic could be drug resistant. Particularly for neoadjuvant therapies such as the tyrosine kinase inhibitors utilized to shrink tumors, it is critical to monitor changes in vascular function and hypoxia to predict treatment efficacy. Current clinical imaging modalities used to obtain structural and functional information regarding hypoxia or oxygen saturation (StO2) do not provide sufficient depth penetration or require the use of exogenous contrast agents. Recently, ultrasound-guided photoacoustic imaging (US-PAI) has garnered significant popularity, as it can noninvasively provide multiparametric information on tumor vasculature and function without the need for contrast agents. Here, we built upon existing literature on US-PAI and demonstrate the importance of changes in StO2 values to predict treatment response, particularly tumor growth rate, when the outcomes are suboptimal. Specifically, we image xenograft mouse models of pancreatic adenocarcinoma treated with suboptimal doses of a tyrosine kinase inhibitor cabozantinib. We utilize the US-PAI data to develop a multivariate regression model that demonstrates that a therapy-induced reduction in tumor growth rate can be predicted with 100% positive predictive power and a moderate (58.33%) negative predictive power when a combination of pretreatment tumor volume and changes in StO2 values pretreatment and immediately posttreatment was employed. Overall, our study indicates that US-PAI has the potential to provide label-free surrogate imaging biomarkers that can predict tumor growth rate in suboptimal therapy.

There is an increasing need for 3D ultrasound and photoacoustic (USPA) imaging technology for real-time monitoring of dynamic changes in vasculature or molecular markers in various malignancies. Current 3D USPA systems utilize expensive 3D transducer arrays, mechanical arms or limited-range linear stages to reconstruct the 3D volume of the object being imaged. In this study, we developed, characterized, and demonstrated an economical, portable, and clinically translatable handheld device for 3D USPA imaging. An off-the-shelf, low-cost visual odometry system (the Intel RealSense T265 camera equipped with simultaneous localization and mapping technology) to track free hand movements during imaging was attached to the USPA transducer. Specifically, we integrated the T265 camera into a commercially available USPA imaging probe to acquire 3D images and compared it to the reconstructed 3D volume acquired using a linear stage (ground truth). We were able to reliably detect 500 µm step sizes with 90.46% accuracy. Various users evaluated the potential of handheld scanning, and the volume calculated from the motion-compensated image was not significantly different from the ground truth. Overall, our results, for the first time, established the use of an off-the-shelf and low-cost visual odometry system for freehand 3D USPA imaging that can be seamlessly integrated into several photoacoustic imaging systems for various clinical applications.