Abstract

The pathophysiological progression of chronic diseases, including atherosclerosis and cancer, is closely related to compositional changes in biological tissues containing endogenous fluorophores such as collagen, elastin, and NADH, which exhibit strong autofluorescence under ultraviolet excitation. Fluorescence lifetime imaging (FLIm) provides robust detection of the compositional changes by measuring fluorescence lifetime, which is an inherent property of a fluorophore. In this paper, we present a dual-modality system combining a multispectral analog-mean-delay (AMD) FLIm and a high-speed swept-source optical coherence tomography (OCT) to simultaneously visualize the cross-sectional morphology and biochemical compositional information of a biological tissue. Experiments using standard fluorescent solutions showed that the fluorescence lifetime could be measured with a precision of less than 40 psec using the multispectral AMD-FLIm without averaging. In addition, we performed ex vivo imaging on rabbit iliac normal-looking and atherosclerotic specimens to demonstrate the feasibility of the combined FLIm-OCT system for atherosclerosis imaging. We expect that the combined FLIm-OCT will be a promising next-generation imaging technique for diagnosing atherosclerosis and cancer due to the advantages of the proposed label-free high-precision multispectral lifetime measurement.

Highlights

  • Fluorescence lifetime imaging (FLIm) [1] is a powerful imaging method that generates an image from the contrast in fluorescence lifetime, which is an intrinsic property of a fluorophore

  • Since the range of interest of the fluorescence lifetime in this study is below about 5 nsec, which corresponds to a fluorescence lifetime of lipoproteins on the higher bandwidth of >460 nm, the under-measurement tendency does not significantly affect the measurement

  • We described the development of a dual-modality system combining a highspeed swept-source optical coherence tomography (OCT) and a multispectral FLIm built based upon the AMD method for high-speed and high-precision fluorescence lifetime measurements to obtain an image with both morphological and biochemical information

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Summary

Introduction

Fluorescence lifetime imaging (FLIm) [1] is a powerful imaging method that generates an image from the contrast in fluorescence lifetime, which is an intrinsic property of a fluorophore. A multispectral FLIm that can provide information about endogenous fluorophores has the ability to characterize changes in composition and the pathophysiological progress in a label-free manner These advantages have led to several studies on FLIm imaging of atherosclerotic plaques [10, 16,17,18], brain tumors [19], oral carcinoma [20, 21], and basal cell carcinoma [22]. These studies demonstrated that FLIm showed superior performance in distinguishing compositions in biological tissues with high accuracy, making FLIm a promising diagnostic technique for atherosclerosis and cancer

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