UC Merced

X-ray luminescence computed tomography (XLCT) is a hybrid molecular imaging modality with the merits of both x-ray imaging (high spatial resolution) and optical imaging (high sensitivity to trace nanophosphors). Narrow x-ray beam based XLCT imaging has shown promise for both the high spatial resolution of X-ray imaging and high molecular sensitivity of optical imaging. However, its slow scan speed limits its applications for in vivo and three-dimensional imaging. We have improved the imaging speed of the pencil beam based XLCT by introducing a fly-scanning scheme. In the fly-scanning scheme, the main factor limiting the scanning speed is the data acquisition time at each interval position. To further increase the imaging speed, we used a gated photon counter (SR400, Stanford Research Systems) to replace the high-speed oscilloscope (MDO3104, Tektronix) to acquire measurement data. The photon counter records much less data without losing acquired signals (the peaks). We have achieved 43 seconds per transverse scan, which is 28.6 times faster than before without compromising the XLCT image quality. To perform quantitative study of pencil beam XLCT in imaging x-ray excitable nanophosphor targets in deep scattering media, we then have scanned a cylindrical agar phantom containing twelve targets filled in with three different phosphor concentrations (2.5 mg/ml, 5 mg/ml, and 10 mg/ml) using an upgraded XLCT imaging system in our laboratory. We have, for the first time, quantitatively analyzed the reconstructed phosphor concentrations of deep targets of pencil beam XLCT and evaluated the performance of filtered back-projection (FBP) algorithm using setups of one, two, and four detectors. Then we have scanned phantoms with 3D printed targets and obtain 3D functional images and 3D structural images simultaneously. Then, based on all the work we have done in XLCT imaging, we have designed, built and developed a first-of-its-kind three-dimensional focused X-ray luminescence tomography (FXLT) imaging system for small animals. There is a co-registered microCT imaging system using a cone beam X-ray tube. We are able to perform both FXLT imaging and a pencil beam based microCT using the superfine focused X-ray tube. The system is specially designed for in vivo imaging of small animals. All the major devices rotate on a powerful rotary gantry while the small animals lie down and keep stationary on a linear stage. We developed a lab-made C++ program to control and automate all data acquisition. We applied a high scanning speed method to obtain high-resolution 3D XLCT images in a reasonable time. To evaluate the performance of the FXLT system, we performed both 2D phantom experiments and 3D phantom experiments and achieved good DICE coefficient. In the end, we have performed mice experiments using the proposed FXLT imaging system. We first have scanned two euthanized nude mice with glass capillary tube targets of different sizes filled with phosphor particles. Then we scanned a live nude mouse with two xenografted tumors for in vivo imaging at four different transverse slices. Before scanning, for each tumor, we intratumorally administrated 0.1 mL of nanoparticle Gd2O2S:Eu3+ solution at a concentration of 1 mg/mL. After the in vivo experiment, the mouse was euthanized. Then, we performed a 10-slice FXLT scan of the euthanized mouse. After all the scans were finished, the tumors were sliced and imaged with an electron-multiplying charged coupled device (EMCCD) camera when excited by a cone beam X-ray tube. Finally, the tumor slices were also scanned by an optical microscope for cross validation. We have, for the first time, reconstructed 3D in vivo XLCT images of nanoparticles at superhigh resolution, which demonstrated that the FXLT system is a power tool in molecular imaging and has the capabilities of performing in vivo and 3D imaging for small animals.