X-ray luminescence optical tomography imaging: experimental studies

Abstract

We present a hybrid imaging modality, x-ray luminescence optical tomography (XLOT), in which collimated x-ray beams are used to excite phosphor-based contrast agents. Images are reconstructed from the optical signals, using the known x-ray beam location and spatial extent as priors. We demonstrate XLOT using phantom experiments with deep targets and show that the reconstructed signal varies by <12% when the depth changes from 4.2 to 7.7 mm. For simple source distributions, we find as few as two orthogonal projection measurements are sufficient for XLOT reconstruction.Hybrid imaging combines the strengths of two imaging modalities. Examples include photoacoustic tomography [1,2] and x-ray acoustic computed tomography [3], in which a pulsed laser or x-ray source, respectively, are used to generate ultrasound inside tissue. Another example is the emerging technique of x-ray luminescence computed tomography (XLCT) that combines the high sensitivity of optical detection with the high spatial resolution of x-ray imaging [4,5]. Here, we propose a related approach, x-ray luminescence optical tomography (XLOT), which utilizes a collimated x-ray beam to excite deep embedded targets together with optical propagation modeling, permitting reconstruction of the distribution of phosphor-particle-based contrast agents in turbid media overlaid on a structural CT image. This overcomes the ill-posedness of the inverse problem in fluorescence and bioluminescence optical tomography [6][7][8] and provides a pathway for high-resolution in vivo optical molecular imaging at significant depths inside tissue.In XLOT, collimated x-ray beams are used to excite contrast agents that have been injected into the subject and are based on phosphor particles such as Eu 3+ -doped gadolinium oxysulfide (GOS:Eu 3+ ). This phosphor has a high cross section for diagnostic energy x rays, excellent light yield, and the emitted light is primarily between 600 and 750 nm, which is good for tissue penetration (Fig. 1). Nanoscale x-ray excitable particles of GOS:Eu 3+ and other Eu 3+ -doped lanthanide compounds have been successfully synthesized [9][10]. These particles can be made biocompatible (e.g., using a gold shell) and ultimately functionalized for molecular imaging applications. *Corresponding author: cli32@ucmerced.edu. Figures 1 and 2(a) show the geometry for XLOT. A collimated x-ray beam is scanned across the sample. Optical photons emitted by GOS particles in the subject are detected with an electron-multiplying charge coupled device (EMCCD). Knowing the volume of the subject excited by the x-ray beam, and using this as prior information, EMCCD measurements are used to reconstruct images of luminescence intensity (proportional to particle concentration), using a model-based reconstruction method similar to fluorescence optical tomography [11]. XLOT retains the advantage of high sensitivity common to optical detection, but its spatial resolution is dependent primarily on the x-ray beam size and is independent of the target depth. The inver...

X-ray luminescence computed tomography imaging based on X-ray distribution model and adaptively split Bregman method

“…al. used a collimated pencil beam X-ray with a beam size of 1 mm diameter to more selectively excite deep targets [8]. However, since the scanning area of the collimated pencil beam X-ray is smaller than narrow beam XLCT, this technology demands relatively longer scanning time under X-ray exposure which limits its application in biology processes.…”

“…[10]. Nevertheless, the introduction of cone beam XLCT may cause limited spatial resolution for deep targets due to light scatter, which is similar to fluorescence molecular tomography (FMT) and bioluminescence tomography (BLT) [8]. Wang et.…”

A wavelet-based single-view reconstruction approach for cone beam x-ray luminescence tomography imaging

“…X-ray luminescence computed tomography (XLCT) has been recently proposed as a new optical molecular imaging modality [1][2][3][4][5][6]. Compared with other optical molecular imaging, e.g., fluorescence molecular tomography (FMT) [7,8] or bioluminescence tomography (BLT) [9,10], an advantage of using XLCT is that autofluorescence can be avoided, which is helpful for improving the sensitivity of imaging.…”

“…In recent years, many efforts have been made to develop new XLCT imaging systems and the corresponding reconstruction methods [1][2][3][4][5][6]. Using a narrow beam XLCT imaging system [1,2], Xing et al firstly reported the tomographic images obtained with XLCT.…”

Monte Carlo simulation of an x-ray luminescence optical tomography scanner prototype

“…A main goal of this technique is that new luminescent nanoparticles could be used as molecular markers, allowing the determination of anatomical and functional information of a living system by combining the high sensitivity of optical imaging and the high spatial resolution of x-ray imaging. In order to test these ideas a couple of XLOT prototypes have been build [3,4] following the basic idea illustrated in Fig. 1.…”