3D Ultrasound-Guided Photoacoustic Imaging to Monitor the Effects of Suboptimal Tyrosine Kinase Inhibitor Therapy in Pancreatic Tumors

Abstract

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.

Ultrasound-guided Photoacoustic image Annotation Toolkit in MATLAB (PHANTOM) for preclinical applications

“…In addition to HbT, StO 2 is an invaluable prognostic marker gathered from multi-wavelength photoacoustic imaging for diagnosis and monitoring of diseases[27, 64, 70, 93]. The StO 2 data of the blood inside the phantom is visualized in 2D and 3D in Fig.…”

“…3B, blue dots) flattened this curve, showing a consistent measurement of HbT as tissue thickness increased. In addition to HbT, StO 2 is an invaluable prognostic marker gathered from multi-wavelength photoacoustic imaging for diagnosis and monitoring of diseases [27,64,70,93].The StO 2 data of the blood inside the phantom is visualized in 2D and 3D in Fig. 4A and Fig.…”

“…The effect is known as spectral coloring and is a well-known confounding factor that compromises the accuracy of blood oxygen saturation (StO 2 ) measurements [22,[24][25][26]. StO 2 has been shown to be a valuable prognostic marker for several clinical and pre-clinical applications and ensuring the accuracy of this parameter will aid in promoting the clinical translation of PAI as an imaging modality [27][28][29][30][31][32][33][34][35][36].…”

Conjugated Nanoparticles for Solid Tumor Theranostics: Unraveling the Interplay of Known and Unknown Factors

“…Many studies have also been done with light-sensitive nanotheranostics for treating solid tumors. However, despite their biocompatibility and light-sensitive ability, this tool’s primary challenge is the drug field’s poor pharmacokinetics. , Additionally, low permeation of light-sensitive drugs via nanotheranostics into the solid tumor is associated with phototoxicity, which stays in the systemic circulation for several weeks, which limits its use as a nanotheranostic. , Photosensitive nanotheranostics also pose the challenge of photobleaching, making room for more improvements. Critical challenges associated with metallic nanotheranostics − include retarded degradation and high cytotoxicity.…”

Multi-spectral photoacoustic imaging combined with acoustic radiation force impulse imaging for applications in tissue engineering

“…To obtain compositional and functional data at ample penetration depths and sufficient resolution while leveraging the advantages of optical contrast, ultrasound based photoacoustic (PA) imaging that relies on the photoacoustic effect to convert optical to acoustic energy may be used. PA imaging traditionally utilizes multi-wavelength sources to capture spectral data which is unmixed to provide the compositional and functional data, most notably highly absorbing contrast agents or blood oxygenation [10][11][12][13][14][15]. PA is commonly combined with US due to their similar receiver electronics and complementary data sets.…”