Abstract

BackgroundIn vivo bioluminescence, fluorescence, and single-photon emission computed tomography (SPECT) imaging provide complementary information about biological processes. However, to date these signatures are evaluated separately on individual preclinical systems. In this paper, we introduce a fully integrated bioluminescence-fluorescence-SPECT platform. Next to an optimization in logistics and image fusion, this integration can help improve understanding of the optical imaging (OI) results.MethodsAn OI module was developed for a preclinical SPECT system (U-SPECT, MILabs, Utrecht, the Netherlands). The applicability of the module for bioluminescence and fluorescence imaging was evaluated in both a phantom and in an in vivo setting using mice implanted with a 4 T1-luc + tumor. A combination of a fluorescent dye and radioactive moiety was used to directly relate the optical images of the module to the SPECT findings. Bioluminescence imaging (BLI) was compared to the localization of the fluorescence signal in the tumors.ResultsBoth the phantom and in vivo mouse studies showed that superficial fluorescence signals could be imaged accurately. The SPECT and bioluminescence images could be used to place the fluorescence findings in perspective, e.g. by showing tracer accumulation in non-target organs such as the liver and kidneys (SPECT) and giving a semi-quantitative read-out for tumor spread (bioluminescence).ConclusionsWe developed a fully integrated multimodal platform that provides complementary registered imaging of bioluminescent, fluorescent, and SPECT signatures in a single scanning session with a single dose of anesthesia. In our view, integration of these modalities helps to improve data interpretation of optical findings in relation to radionuclide images.

Highlights

  • In vivo bioluminescence, fluorescence, and single-photon emission computed tomography (SPECT) imaging provide complementary information about biological processes

  • Fluorescence techniques suffer from tissue autofluorescence, resulting in an unwanted background signal. These negative features can be partly overcome by using emissions in the near-infrared (NIR) spectrum, but optical imaging cannot equal the detailed view and quantitative accuracy that SPECT provides at larger depths

  • We developed and tested a low-cost prototype system consisting of an add-on planar bioluminescence/fluorescence optical module for a dedicated small animal SPECT device (U-SPECTII, MILabs B.V., Utrecht, the Netherlands) [21,22,23,24]

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Summary

Introduction

Fluorescence, and single-photon emission computed tomography (SPECT) imaging provide complementary information about biological processes. Studies of human disease in animal models often provide an essential link between chemistry, fundamental research at the molecular level, and the development/ evaluation of new diagnostic and therapeutic methods. Molecular imaging modalities such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), bioluminescence, and fluorescence. Fluorescence techniques suffer from tissue autofluorescence, resulting in an unwanted background signal These negative features can be partly overcome by using emissions in the near-infrared (NIR) spectrum, but optical imaging cannot equal the detailed view and quantitative accuracy that SPECT provides at larger depths. One of the great challenges today is to place these two modalities in perspective and to determine the added value of optical imaging within the field of nuclear medicine [9]

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