Abstract

To date, few optical imaging systems are available in clinical practice to perform noninvasive measurements transcutaneously. Instead, functional imaging is performed using ionizing radiation or intense magnetic fields in most cases. The applicability of fluorescence imaging (e.g., for the detection of fluorescently labeled objects, such as tumors) is limited due to the restricted tissue penetration of light and the required long exposure time. Thus, the development of highly sensitive and easily manageable instruments is necessary to broaden the utility of optical imaging. To advance these developments, an improved fluorescence imaging system was designed in this study that operates on the principle of noncontact laser-induced fluorescence and enables the detection of fluorescence from deeper tissue layers as well as real-time imaging. The high performance of the developed optical laser scanner results from the combination of specific point illumination, an intensified charge-coupled device (ICCD) detector with a novel light trap, and a filtering strategy. The suitability of the laser scanner was demonstrated in two representative applications and an in vivo evaluation. In addition, a comparison with a planar imaging system was performed. The results show that the exposure time with the developed laser scanner can be reduced to a few milliseconds during measurements with a penetration depth of up to 32 mm. Due to these short exposure times, real-time fluorescence imaging can be easily achieved. The ability to measure fluorescence from deep tissue layers enables clinically relevant applications, such as the detection of fluorescently labeled malignant tumors.

Highlights

  • The International Cancer Research Agency has estimated that more than 8.2 million people died of cancer in 2012 [1]

  • In currently available optical imaging systems, high fluorescent dye concentrations and/or a high laser power combined with a sensitive low-noise charge-coupled device (CCD) or complementary metal-oxide-semiconductor (CMOS) detectors are required for the imaging of deep tissue layers [10,25,28]

  • Experiments to detect fluorescence originating from deep tissue layers were performed to determine the maximum penetration depth in tissue achievable using the developed laser scanner

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Summary

Introduction

The International Cancer Research Agency has estimated that more than 8.2 million people died of cancer in 2012 [1]. Optical imaging provides a highly sensitive and cost-effective imaging technique for use with tissues and diseases and is worth exploring further [4,7,8,9,10,11]. A common problem is that light from the secondary light path is multiply scattered due to the tissue properties, and the objects cannot be sharply imaged. This reduces the resolution of the imaging system. An additional disadvantage of the present noncontact CW in vivo optical imaging systems is that their low signal intensities require the use of long integration times to produce acceptable images with sufficient signal-to-noise ratios (SNRs) [33]

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