Quadruple ultrasound, photoacoustic, optical coherence, and fluorescence fusion imaging with a transparent ultrasound transducer

Significance

Multimodal imaging based on optics and ultrasound can provide guide images and complementary structural and functional information, thus improving the accuracy of medical diagnosis and treatment monitoring. However, because conventional ultrasound transducers are opaque, in multimodal imaging with optics, the optical devices must be placed off-axis from the ultrasound transducer. This off-axis arrangement is prone to misalignment, adds complexity and bulk to the system, and can result in a low signal-to-noise-ratio. Here, we present a transparent ultrasound transducer at the heart of a quadruple fusion imaging system that seamlessly integrates ultrasound imaging, photoacoustic imaging, optical coherence tomography, and fluorescence imaging, and we demonstrate the system’s use in imaging responses to both ophthalmologic injuries and oncologic diseases.

Abstract

Ultrasound and optical imagers are used widely in a variety of biological and medical applications. In particular, multimodal implementations combining light and sound have been actively investigated to improve imaging quality. However, the integration of optical sensors with opaque ultrasound transducers suffers from low signal-to-noise ratios, high complexity, and bulky form factors, significantly limiting its applications. Here, we demonstrate a quadruple fusion imaging system using a spherically focused transparent ultrasound transducer that enables seamless integration of ultrasound imaging with photoacoustic imaging, optical coherence tomography, and fluorescence imaging. As a first application, we comprehensively monitored multiparametric responses to chemical and suture injuries in rats’ eyes in vivo, such as corneal neovascularization, structural changes, cataracts, and inflammation. As a second application, we successfully performed multimodal imaging of tumors in vivo, visualizing melanomas without using labels and visualizing 4T1 mammary carcinomas using PEGylated gold nanorods. We strongly believe that the seamlessly integrated multimodal system can be used not only in ophthalmology and oncology but also in other healthcare applications with broad impact and interest.