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.

Highlights

  • Ultrasound and optical imagers are used widely in a variety of biological and medical applications

  • In a system combining optical coherence tomography (OCT) and US imaging (USI), OCT mainly images microscopic structures and functions of tissues at depths within a couple of millimeters, whereas USI, because it is based on acoustic phenomena, provides similar image information in deep tissues [14]

  • We present a practical LNO-based single-crystal TUT and a quadruple fusion imaging system for ophthalmologic and oncologic applications that seamlessly integrates USI, photoacoustic imaging (PAI), OCT, and fluorescence imaging (FLI) via the TUT

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Summary

MEDICAL SCIENCES

Photoacoustic, optical coherence, and fluorescence fusion imaging with a transparent ultrasound transducer. To investigate the in vivo capability of our quadruple fusion imaging system with the TUT, we monitored rats’ eyes after inflicting alkali burn (n = 5) and suture (n = 6) injuries After such injuries, the eye exhibits one or more of the following changes related to serious vision loss, such as CNV, morphological changes, fibrous membrane and edema induced by inflammation, and cataracts. The PA signals from the blood vessels decrease, possibly because the PEG-GNRs may have accumulated in the skin layer and absorbed the light from the skin surface This possibility can be confirmed by the strong PA signals from the skin layer shown in the B-scan images (Fig. 7 A, 8 and 9, cut along lines “i” and “ii” of Fig. 7 A, 7).

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