Quantitative Imaging of Gd Nanoparticles in Mice Using Benchtop Cone-Beam X-ray Fluorescence Computed Tomography System.

Siyuan Zhang,Zhiqiang Chen,Liang Li,Wenli Zhang,Hongbing Lu,Jiayou Chen

doi:10.3390/ijms20092315

Abstract

Nanoparticles (NPs) are currently under intensive research for their application in tumor diagnosis and therapy. X-ray fluorescence computed tomography (XFCT) is considered a promising non-invasive imaging technique to obtain the bio-distribution of nanoparticles which include high-Z elements (e.g., gadolinium (Gd) or gold (Au)). In the present work, a set of experiments with quantitative imaging of GdNPs in mice were performed using our benchtop XFCT device. GdNPs solution which consists of 20 mg/mL NaGdF4 was injected into a nude mouse and two tumor-bearing mice. Each mouse was then irradiated by a cone-beam X-ray source produced by a conventional X-ray tube and a linear-array photon counting detector with a single pinhole collimator was placed on one side of the beamline to record the intensity and spatial information of the X-ray fluorescent photons. The maximum likelihood iterative algorithm with scatter correction and attenuation correction method was applied for quantitative reconstruction of the XFCT images. The results show that the distribution of GdNPs in each target slice (containing liver, kidney or tumor) was well reconstructed and the concentration of GdNPs deposited in each organ was quantitatively estimated, which indicates that this benchtop XFCT system provides convenient tools for obtaining accurate concentration distribution of NPs injected into animals and has potential for imaging of nanoparticles in vivo.

Highlights

Nanoparticle drugs are currently under intensive research for their application in tumor diagnosis and therapy [1,2]
The phantom was scanned by Cone-beam computed tomography (CBCT) and one axial slice was selected to perform X-ray fluorescence computed tomography (XFCT) scan (Figure 1c)
It is noticed that the reconstructed values of XFCT images are accurate only when the scatter background is removed and the attenuation of incident beam and X-ray fluorescent (XRF) photons in the object are corrected

Summary

Introduction

Nanoparticle drugs are currently under intensive research for their application in tumor diagnosis and therapy [1,2]. As research on the medicinal property and application of nanoparticle drugs relies on in vivo experiments, a noninvasive detection technique is necessary for researchers to obtain the real-time information of the drugs injected into the animals. The approach of nanoparticle detection and quantitative imaging has become a research hotspot in recent years. Fluorescence based imaging of nanoparticles is a widely used technique for biomedical imaging [3]. As hemoglobin and water have a lower absorption coefficient in the near-infrared (NIR) region (650–900 nm) compared with the visible region, NIR fluorescence imaging is routinely used for imaging of deeper tissues [4,5,6]. As it is known that characteristic X-rays ( called X-ray fluorescence) stimulated from atoms have much higher energies and penetrability than visible light photons, X-ray fluorescence imaging may further increase the imaging sensitivity of deeper organs

Methods

Results

Conclusion