Imaging of X-Ray-Excited Emissions from Quantum Dots and Biological Tissue in Whole Mouse

Sean G Ryan,Martin Pule,Matthew N Butler,Segun S Adeyemi,May Zaw Thin,Tammy Kalber,Mark F Lythgoe,Ian F Harrison,P Stephen Patrick,Daniel J Stuckey

doi:10.1038/s41598-019-55769-5

Sean G Ryan, Martin Pule + Show 8 more

Open Access

https://doi.org/10.1038/s41598-019-55769-5

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Abstract

Optical imaging in clinical and preclinical settings can provide a wealth of biological information, particularly when coupled with targetted nanoparticles, but optical scattering and absorption limit the depth and resolution in both animal and human subjects. Two new hybrid approaches are presented, using the penetrating power of X-rays to increase the depth of optical imaging. Foremost, we demonstrate the excitation by X-rays of quantum-dots (QD) emitting in the near-infrared (NIR), using a clinical X-ray system to map the distribution of QDs at depth in whole mouse. We elicit a clear, spatially-resolved NIR signal from deep organs (brain, liver and kidney) with short (1 second) exposures and tolerable radiation doses that will permit future in vivo applications. Furthermore, X-ray-excited endogenous emission is also detected from whole mouse. The use of keV X-rays to excite emission from QDs and tissue represent novel biomedical imaging technologies, and exploit emerging QDs as optical probes for spatial-temporal molecular imaging at greater depth than previously possible.

Highlights

Over the last four decades, biomedical imaging has revolutionised preclinical and clinical medicine with highly detailed structural and functional scanning
Our measurements have shown that X-ray excitation of NIR emission from CdTe core-type Quantum dots (QDs) and ZnCuInS/ ZnS core-shell QDs can be achieved using clinically-relevant X-ray energies (20–120 keV) and doses, and that the emission is intense enough to be imaged in 1 sec using a sensitive EM-CCD detector
This result ushers in a new, practical and convenient biomedical imaging technology that benefits from a gain in the depth of imaging due to the penetrating power of X-rays compared to UV/optical exciters of fluorescence, yielding NIR emission that experiences low absorption by water and blood[1]

Summary

Introduction

Over the last four decades, biomedical imaging has revolutionised preclinical and clinical medicine with highly detailed structural and functional scanning. One approach aimed at overcoming these limitations uses penetrating X-rays to excite radio-luminescent nanoparticles in such a way that optical/near-infrared (NIR) light emitted can be detected externally. These techniques include X-ray luminescence computed tomography (XLCT)[6,7,8,9], known as X-ray radio-luminescence CT and X-ray scintillation CT, where the scintillating chemical is often the rare-earth phosphor Eu (e.g. Gd2O2S:Eu, BaYF5:Eu3+, Gd2O3:Eu3+)[9,10], and X-ray luminescent optical tomography (XLOT) utilising Gd2O2S:Eu3+11. Excess signal in ROI (relative to water control) for four CdTe concentrations: 0.016 mg 0.13 mg 0.46 mg [photons s−1]

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