Focused x-ray luminescence imaging system for small animals based on a rotary gantry

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.

Development of fast and three-dimensional focused x-ray luminescence tomography system

“…We are scanning both euthanize mice with inserted capillary tubes as targets and in vivo mice with tumor targets and the experimental results will be reported soon. We will also use the machine learning algorithms for better XLCT reconstruction and will apply the bright nanoparticle to save the measurement time further [11].…”

“…A PMT (H8259-01, Hamamatsu) connected with the scintillator via light guide was also mounted on the gantry. We used a heavy-duty linear stage (NLS4-20-12, Newmark Systems Inc.) to translate the XOS X-ray tube at a high speed and a good position precision [11]. The heavy-duty linear stage was also mounted on the rotary gantry.…”

“…Furthermore, we have showed that the data acquisition time can be further reduced by using a gated photon counter to replace the high-speed oscilloscope [10]. In another work, we have developed a deep-learning based reconstruction algorithm to reduce the number of angular projection views [11]. To perform multi-color FXLT imaging, we have synthesized biocompatible nanophosphors with bright and distinct X-ray luminescence spectra and compared them with commercially available nanophosphors [12].…”

Oxygenation imaging in deep tissue with x-ray luminescence computed tomography (XLCT)

“…Figure 3 shows photos of the XLCT imaging systems with two measurement fiber bunders. The XLCT imaging system has been described in other publications [6][7][8][9][10][11][12][13]. Briefly, an X-ray tube (X-Beam Powerflux [Mo anode], XOS) was operated at 30 KVp and 0.5 mA with the beam diameter of 100 m.…”

“…In this work, we proposed an imaging approach to measure the oxygenation concentration in deep tissues, based on the XLCT system [6][7][8][9][10][11][12][13], with the combined strengths of high measurement sensitivity and high spatial resolution. The proposed method measures the oxygen concentration by exciting X-ray scintillators which emits optical photons to excite oxygen-dependent phosphorescence dyes [14].…”