Abstract

.Significance: The ability to detect and localize specific molecules through tissue is important for elucidating the molecular basis of disease and treatment. Unfortunately, most current molecular imaging tools in tissue either lack high spatial resolution (e.g., diffuse optical fluorescence tomography or positron emission tomography) or lack molecular sensitivity (e.g., micro-computed tomography, ). X-ray luminescence imaging emerged about 10 years ago to address this issue by combining the molecular sensitivity of optical probes with the high spatial resolution of x-ray imaging through tissue. In particular, x-ray luminescence computed tomography (XLCT) has been demonstrated as a powerful technique for the high-resolution imaging of deeply embedded contrast agents in three dimensions (3D) for small-animal imaging.Aim: To facilitate the translation of XLCT for small-animal imaging, we have designed and built a small-animal dedicated focused x-ray luminescence tomography (FXLT) scanner with a scanner, synthesized bright and biocompatible nanophosphors as contrast agents, and have developed a deep-learning-based reconstruction algorithm.Approach: The proposed FXLT imaging system was designed using computer-aided design software and built according to specifications. nanophosphors doped with europium or terbium were synthesized with a silica shell for increased biocompatibility and functionalized with biotin. A deep-learning-based XLCT image reconstruction was also developed based on the residual neural network as a data synthesis method of projection views from few-view data to enhance the reconstructed image quality.Results: We have built the FXLT scanner for small-animal imaging based on a rotational gantry. With all major imaging components mounted, the motor controlling the gantry can be used to rotate the system with a high accuracy. The synthesized nanophosphors displayed distinct x-ray luminescence emission, which enables multi-color imaging, and has successfully been bound to streptavidin-coated substrates. Lastly, numerical simulations using the proposed deep-learning-based reconstruction algorithm has demonstrated a clear enhancement in the reconstructed image quality.Conclusions: The designed FXLT scanner, synthesized nanophosphors, and deep-learning-based reconstruction algorithm show great potential for the high-resolution molecular imaging of small animals.

Highlights

  • During the past decade, the concept of x-ray luminescence imaging (XLI) emerged and demonstrated great potential for molecular imaging in small animals by combining the high-spatial resolution of traditional x-ray imaging and the superb measurement sensitivity of optical imaging

  • Lun et al.: Focused x-ray luminescence imaging system for small animals based on a rotary gantry optical fiber bundle

  • We have first shown the design and build of our small-animal dedicated focused x-ray luminescence tomography (FXLT) scanner that can perform both μCT imaging and 3D high-resolution x-ray luminescence computed tomography (XLCT) imaging in one system

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Summary

Introduction

The concept of x-ray luminescence imaging (XLI) emerged and demonstrated great potential for molecular imaging in small animals by combining the high-spatial resolution of traditional x-ray imaging and the superb measurement sensitivity of optical imaging. A focused or collimated beam of x-ray photons are used to penetrate deeply through the tissue samples, with minimal scatter; x-ray excitable contrast agents within the x-ray beam path absorb the x-ray energy, causing a photophysical cascade of events, eventually leading to the emission of many optical photons, which can pass through the tissue and escape from the skin. Sensitive photodetectors, such as electron multiplying chargecoupled device (EMCCD) cameras or photomultiplier tubes (PMTs), can detect the optical photons for image reconstruction. Several research groups, including our own, improved several aspects of XLCT including the XLCT imaging systems,[3,4,5,6,7,8,9,10,11,12,13] robust reconstruction algorithms,[4,14] and designing efficient, bright, and biocompatible XLCT imaging probes.[15,16,17,18,19,20]

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