Abstract
Photoacoustic (PA) imaging has shown tremendous promise for imaging tumor vasculature and its function at deeper penetration depths without the use of exogenous contrast agents. Traditional PA imaging systems employ expensive and bulky class IV lasers with low pulse repetition rate, due to which its availability for preclinical cancer research is hampered. In this study, we evaluated the capability of a Light-Emitting Diode (LED)-based PA and ultrasound (US) imaging system for monitoring heterogeneous microvasculature in tumors (up to 10 mm in depth) and quantitatively compared the PA images with gold standard histology images. We used a combination of a 7 MHz linear array US transducer and 850 nm excitation wavelength LED arrays to image blood vessels in a subcutaneous tumor model. After imaging, the tumors were sectioned and stained for endothelial cells to correlate with PA images across similar cross-sections. Analysis of 30 regions of interest in tumors from different mice showed a statistically significant R-value of 0.84 where the areas with high blood vessel density had high PA response while low blood vessel density regions had low PA response. Our results confirm that LED-based PA and US imaging can provide 2D and 3D images of tumor vasculature and the potential it has as a valuable tool for preclinical cancer research.
Highlights
The critical role of vasculature for tumor growth and metastasis is undisputed
Stain of frames that did not have motion artifacts were used for image analysis. (B) Hematoxylin and Eosin (H&E) stainthe of the tumor cross‐section
1–2 cm in diameter, and orthotopic tumors depending on the organ can vary between subcutaneous tumors is less than 1–2 cm in diameter, and orthotopic tumors depending on the organ3 andvary
Summary
The critical role of vasculature for tumor growth and metastasis is undisputed. Tumor aggressiveness and the extent of the aberrant tumor vascular structure and function are highly correlated.To meet the increasing needs for oxygen and nutrients, cancers induce neovascularization, one of the hallmarks of cancer [1]. Tumor aggressiveness and the extent of the aberrant tumor vascular structure and function are highly correlated. Many anti-angiogenic agents or therapies that can prune these blood vessels and prevent nutrients from reaching the tumors have been developed [5]. Several imaging modalities have been used to study changes in tumor vasculature both at structural and functional level. PA imaging involves detection of acoustic waves generated when the optical absorbers such as hemoglobin in the blood are irradiated with nanosecond pulsed light and undergo thermo-elastic expansion and contraction [11]. The acoustic waves are picked up by the ultrasound (US) transducer and processed to generate a PA image [11,12]. Two features of PA imaging that make it highly suitable to image vasculature are: 1. Two features of PA imaging that make it highly suitable to image vasculature are: 1. ability to image blood vessels
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