X-ray Luminescence Computed Tomography Imaging Research Articles

Oxygenation imaging in deep tissue with X-Ray luminescence computed tomography (XLCT).

Oxygenation concentration of tissue is an important factor in culturing stem cells and in studying the therapy response of cancer cells. The hypoxia bone marrow is the site to harbor cancer cells. Thus, direct high-resolution measurements of molecular 𝑂2 would provide powerful means of monitoring cultured stem cells and therapied cancer cells. We proposed an imaging approach to measure oxygenation concentration in deep tissues, based on the XLCT, with combined strengths of high chemical sensitivity and high spatial resolution. We have developed different biosensing films for oxygenation measurements and tested these films with X-ray luminescent experiments. We have also performed phantom experiments with multiple targets to validate the XLCT imaging system with measurements at two channels.

Superfast Scan of Focused X-Ray Luminescence Computed Tomography Imaging.

X-ray luminescence computed tomography (XLCT) is a hybrid molecular imaging modality having the high spatial resolution of x-ray imaging and high measurement sensitivity of optical imaging. Narrow x-ray beam based XLCT imaging has shown promise for high spatial resolution imaging of luminescent targets in deep tissues, but the slow acquisition speed limits its applications. In this work, we have introduced a superfast XLCT scan scheme based on the photon counter detector and a fly-scanning method. The new scan scheme is compared with three other scan methods. We have also designed and built a single-pixel x-ray detector to detect object boundaries automatically. With the detector, we can perform the parallel beam CT imaging with the XLCT imaging simultaneously. We have built the prototype XLCT imaging system to verify the proposed scan scheme. A phantom embedded with a set of four side-by-side cylindrical targets was scanned. With the proposed superfast scan scheme, we have achieved 43 seconds per transverse scan, which is 28.6 times faster than before with slightly better XLCT image quality. The superfast scan allows us to perform 3D pencil beam XLCT imaging in the future.

Super-Fast Three-Dimensional Focused X-ray Luminescence Computed Tomography with a Gated Photon Counter.

X-ray luminescence computed tomography (XLCT) is a hybrid molecular imaging modality combining the merits of both x-ray imaging (high spatial resolution) and optical imaging (high sensitivity to tracer nanophosphors). Narrow x-ray beam based XLCT imaging has shown promise for high spatial resolution imaging, but the slow acquisition speed limits its applications for in vivo imaging. We introduced a continuous scanning scheme to replace the selective excitation scheme to improve imaging speed in a previous study. Under the continuous scanning scheme, the main factor that limits the scanning speed is the data acquisition time at each interval position. In this work, we have used a gated photon counter (SR400, Stanford Research Systems) to replace the high-speed oscilloscope (MDO3104, Tektronix) to acquire measurement data. The gated photon counter only counts the photon peaks in each measurement interval, while the oscilloscope records the entire waveform including both background noise data and photon peak data. The photon counter records much less data without losing any relevant information, which makes it ideal for super-fast three-dimensional (3D) imaging. We have built prototype XLCT imaging systems of both types and performed both single target and multiple target phantom experiments in 3D. The results have verified the feasibility of our proposed photon counter based system and good 3D imaging capabilities of XLCT within a reasonable time, yielding a 14 times faster scanning time compared with the oscilloscope based XLCT system. Now, the total scan time is reduced to 27 seconds per transverse section.

OPK_SNCA: Optimized prior knowledge via sparse non-convex approach for cone-beam X-ray luminescence computed tomography imaging

BackgroundThe development of Cone-beam X-ray luminescence computed tomography (CB-XLCT) has allowed the quantitative in-depth biological imaging, but with a greatly ill-posed and ill-conditioned inverse problem. Although the predefined permissible source region (PSR) is a widely used way to alleviate the problem for CB-XLCT imaging, how to obtain the accurate PSR is still a challenge for the process of inverse reconstruction. MethodsWe proposed an optimized prior knowledge via a sparse non-convex approach (OPK_SNCA) for CB-XLCT imaging. Firstly, non-convex Lp-norm optimization model was employed for copying with the inverse problem, and an iteratively reweighted split augmented lagrangian shrinkage algorithm was developed to obtain a group of sparse solutions based on different non-convex p values. Secondly, a series of permissible regions (PRs) with different discretized mesh was further achieved, and the intersection operation was implemented on the group of PRs to get a reasonable PSR. After that, the final PSR was adopted as an optimized prior knowledge to enhance the reconstruction quality of inverse reconstruction. ResultsBoth simulation experiments and in vivo experiment were performed to evaluate the efficiency and robustness of the proposed method. ConclusionsThe experimental results demonstrated that our proposed method could significantly improve the imaging quality of the distribution of X-ray-excitable nanophosphors for CB-XLCT.

Sparse-View Cone-Beam X-Ray Luminescence Computed Tomography Imaging for Optimized Regional Prior Knowledge

Sparse-View Cone-Beam X-Ray Luminescence Computed Tomography Imaging for Optimized Regional Prior Knowledge

Radiation dose estimation for pencil beam X-ray luminescence computed tomography imaging.

Pencil beam X-ray luminescence computed tomography (XLCT) imaging provides superior spatial resolution than other imaging geometries like sheet beam and cone beam geometries. However, the pencil beam geometry suffers from long scan times, resulting in concerns overdose which discourages the use of pencil beam XLCT. The dose deposited in pencil beam XLCT imaging was investigated to estimate the dose from one angular projection scan with three different X-ray sources. The dose deposited in a typical small animal XLCT imaging was investigated. A Monte Carlo simulation platform, GATE (Geant4 Application for Tomographic Emission) was used to estimate the dose from one angular projection scan of a mouse leg model with three different X-ray sources. Dose estimations from a six angular projection scan by three different X-ray source energies were performed in GATE on a mouse trunk model composed of muscle, spine bone, and a tumor. With the Sigray source, the bone marrow of mouse leg was estimated to have a radiation dose of 44 mGy for a typical XLCT imaging with six angular projections, a scan step size of 100 micrometers, and 106 X-ray photons per linear scan. With the Sigray X-ray source and the typical XLCT scanning parameters, we estimated the dose of spine bone, muscle tissues, and tumor structures of the mouse trunk were 38.49 mGy, 15.07 mGy, and 16.87 mGy, respectively. Our results indicate that an X-ray benchtop source (like the X-ray source from Sigray Inc.) with high brilliance and quasi-monochromatic properties can reduce dose concerns with the pencil beam geometry. Findings of this work can be applicable to other imaging modalities like X-ray fluorescence computed tomography if the imaging protocol consists of the pencil beam geometry.

Restarted primal–dual Newton conjugate gradient method for enhanced spatial resolution of reconstructed cone-beam x-ray luminescence computed tomography images

Cone-beam x-ray luminescence computed tomography (CB-XLCT) has been proposed as a promising imaging tool, which enables three-dimensional imaging of the distribution of nanophosphors (NPs) in small animals. However, the reconstruction performance is usually unsatisfactory in terms of spatial resolution due to the ill-posedness of the CB-XLCT inverse problem. To alleviate this problem and to achieve high spatial resolution, a reconstruction method consisting of inner and outer iterations based on a restarted strategy is proposed. In this method, the primal–dual Newton conjugate gradient method (pdNCG) is adopted in the inner iterations to get fast reconstruction, which is used for resetting the permission region and increasing the convergence speed of the outer iteration. To assess the performance of the method, both numerical simulation and physical phantom experiments were conducted with a CB-XLCT system. The results demonstrate that compared with conventional reconstruction methods, the proposed re-pdNCG method can accurately and efficiently resolve the adjacent NPs with the least relative error.

High-resolution x-ray luminescence computed tomography.

High-resolution imaging modalities play a critical role for advancing biomedical sciences. Recently, x-ray luminescence computed tomography (XLCT) imaging was introduced as a hybrid molecular imaging modality that combines the high-spatial resolution of x-ray imaging and molecular sensitivity of optical imaging. The narrow x-ray beam based XLCT imaging has been demonstrated to achieve high spatial resolution, even at depth, with great molecular sensitivity. Using a focused x-ray beam as the excitation source, orders of magnitude of increased sensitivity has been verified compared with previous methods with a collimated x-ray beam. In this work, we demonstrate the high-spatial resolution capabilities of our focused x-ray beam based XLCT imaging system by scanning two sets of targets, differing in the target size, embedded inside of two tissue-mimicking cylindrical phantoms. Gd2O2S:Eu3+ targets of 200 µm and 150 µm diameters were created and embedded with the same edge-to-edge distances as their diameters respectively. We scanned and reconstructed a single transverse section and successfully demonstrated that a focused x-ray beam with an average dual-cone size of 125 µm could separate the targets in both phantoms with good shape and location accuracy. We have also improved the current XLCT imaging system to make it feasible for fast three-dimensional XLCT scanning.

X-ray luminescence imaging for small animals.

X-ray luminescence imaging emerged for about a decade and combines both the high spatial resolution of x-ray imaging with the high measurement sensitivity of optical imaging, which could result in a great molecular imaging tool for small animals. So far, there are two types of x-ray luminescence computed tomography (XLCT) imaging. One uses a pencil beam x-ray for high spatial resolution at a cost of longer measurement time. The other uses cone beam x-ray to cover the whole mouse to obtain XLCT images at a very short time but with a compromised spatial resolution. Here we review these two methods in this paper and highlight the synthesized nanophosphors by different research groups. We are building a focused x-ray luminescence tomography (FXLT) imaging system, developing a machine-learning based FXLT reconstruction algorithm, and synthesizing nanophosphors with different emission wavelengths. In this paper, we will report our current progress from these three aspects. Briefly, we mount all main components, including the focused x-ray tube, the fiber detector, and the x-ray tube and x-ray detector for a microCT system, on a rotary which is a heavy-duty ring track. A microCT scan will be performed before FXLT scan. For a FXLT scan, we will have four PMTs to measure four fiber detectors at two different wavelengths simultaneously for each linear scan position. We expect the spatial resolution of the FXLT imaging will be around 100 micrometers and a limit of detection of approximately 2 μg/mL (for Gd2O2S:Eu).

Method for improving the spatial resolution of narrow x-ray beam-based x-ray luminescence computed tomography imaging.

.X-ray luminescence computed tomography (XLCT) is an emerging hybrid imaging modality which has the potential for achieving both high sensitivity and spatial resolution simultaneously. For the narrow x-ray beam-based XLCT imaging, based on previous work, a spatial resolution of about double the x-ray beam size can be achieved using a translate/rotate scanning scheme, taking step sizes equal to the x-ray beam width. To break the current spatial resolution limit, we propose a scanning strategy achieved by reducing the scanning step size to be smaller than the x-ray beam size. We performed four sets of numerical simulations and a phantom experiment using cylindrical phantoms and have demonstrated that our proposed scanning method can greatly improve the XLCT-reconstructed image quality compared with the traditional scanning approach. In our simulations, by using a fixed x-ray beam size of 0.8 mm, we were able to successfully reconstruct six embedded targets as small as 0.5 mm in diameter and with the same edge-to-edge distances by using a scanning step as small as 0.2 mm which is a 1.6 times improvement in the spatial resolution compared with the traditional approach. Lastly, the phantom experiment further demonstrated the efficacy of our proposed method in improving the XLCT image quality, with all image quality metrics improving as the step size decreased.

Focused x-ray luminescence computed tomography: experimental studies.

X-ray luminescence computed tomography (XLCT) is an emerging hybrid molecular imaging modality and has shown great promises in overcoming the strong optical scattering in deep tissues. Though the narrow x-ray beam based XLCT imaging has been demonstrated to obtain high spatial resolution at depth, it suffers from a relatively long measurement time, hindering its practical applications. Recently, we have designed a focused x-ray beam based XLCT imaging system and have successfully performed imaging in about 7.5 seconds per section for a mouse sized object. However, its high spatial resolution capacity has not been fully implemented yet. In this paper, with a superfine focused x-ray beam we design a focused-x-ray luminescence tomography (FXLT) system for spatial resolution up to 94 μm. First, we have described our design in details. Then, we estimate the performance of the designed FXLT imaging system. Lastly, we have found that the spatial resolution of FXLT can be further improved by reducing the scan step size, which has been demonstrated by numerical simulations.

Background luminescence in x-ray luminescence computed tomography (XLCT) imaging.

X-ray luminescence computed tomography (XLCT) is an emerging hybrid imaging modality. It has been recently reported that materials such as water, tissue, or even air can generate optical photons upon x-ray irradiation, which can increase the noises in measurements of XLCT. In this study, we have investigated the x-ray luminescence from water, air, as well as tissue mimicking phantoms, including one embedded with a 0.01mg/mL GOS:Eu3+ microphosphor target. We have measured the optical emission spectrum from each sample, including samples of meat and fat, using a spectrograph. Our results indicate that there are plenty of optical photons emitted by x-ray irradiation, and a small nanophosphor concentration, as low as 5.28μM in a deep background, can provide enough contrast for XLCT imaging.

X-ray luminescence computed tomography using a focused x-ray beam.

Due to the low x-ray photon utilization efficiency and low measurement sensitivity of the electron multiplying charge coupled device camera setup, the collimator-based narrow beam x-ray luminescence computed tomography (XLCT) usually requires a long measurement time. We, for the first time, report a focused x-ray beam-based XLCT imaging system with measurements by a single optical fiber bundle and a photomultiplier tube (PMT). An x-ray tube with a polycapillary lens was used to generate a focused x-ray beam whose x-ray photon density is 1200 times larger than a collimated x-ray beam. An optical fiber bundle was employed to collect and deliver the emitted photons on the phantom surface to the PMT. The total measurement time was reduced to 12.5min. For numerical simulations of both single and six fiber bundle cases, we were able to reconstruct six targets successfully. For the phantom experiment, two targets with an edge-to-edge distance of 0.4mm and a center-to-center distance of 0.8mm were successfully reconstructed by the measurement setup with a single fiber bundle and a PMT.

Collimated superfine x-ray beam based x-ray luminescence computed tomography.

X-ray luminescence computed tomography (XLCT) is a hybrid imaging modality with the potential to achieve a spatial resolution up to several hundred micrometers for targets embedded in turbid media with a depth larger than several millimeters. In this paper, we report a high spatial resolution XLCT imaging system with a collimated superfine x-ray beam in imaging the deeply embedded targets. A collimator with a 100 micrometer pinhole was mounted in the front of a powerful x-ray tube to generate a superfine x-ray pencil beam with a beam diameter of 0.175 mm. For the phantom experiment of four capillary targets with an edge-to-edge distance of 400 micrometers, we were able to reconstruct the targets in a depth of 5 mm successfully, which were validated with microCT images. We have further investigated the effect of different x-ray beam diameters on the reconstructed XLCT images with numerical simulations. Our results indicate that XLCT has the ability to image successfully multiple deeply embedded targets when the collimated x-ray beam diameter is less than or equal to the target edge-to-edge distance. Our numerical simulations also demonstrate that XLCT can achieve a spatial resolution of 200 micrometers for targets embedded at a depth of 5 mm if the scanning beam has a diameter of 100 micrometers.

Sub-10 nm Water-Dispersible β-NaGdF4:X% Eu3+ Nanoparticles with Enhanced Biocompatibility for in Vivo X-ray Luminescence Computed Tomography.

As a novel molecular and functional imaging modality, X-ray luminescence computed tomography (XLCT) has shown its potentials in biomedical and preclinic applications. However, there are still some limitations of X-ray-excited luminescent materials, such as low luminescence efficiency, poor biocompatibility, and cytotoxicity, making in vivo XLCT imaging quite challenging. In this study, for the very first time, we present on using sub-10 nm β-NaGdF4:X% Eu3+ nanoparticles with poly(acrylic acid) (PAA) surface modification, which demonstrate outstanding luminescence efficiency, uniform size distribution, water dispersity, and biosafety, as the luminescent probes for in vivo XLCT application. The pure hexagonal phase (β-) NaGdF4 has been successfully synthesized and characterized by X-ray powder diffraction (XRD) and transmission electron microscopy (TEM), and then the results of X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectrometry (EDX), and elemental mapping further confirm Eu3+ ions doped into NaGdF4 host. Under X-ray excitation, the β-NaGdF4 nanoparticles with a doping level of 15% Eu3+ exhibited the most efficient luminescence intensity. Notably, the doping level of Eu3+ has no effect on the crystal phase and morphology of the NaGdF4-based host. Afterward, β-NaGdF4:15% Eu3+ nanoparticles were modified with PAA to enhance the water dispersity and biocompatibility. The compatibility of in vivo XLCT imaging using such nanoparticles was systematically studied via in vitro cytotoxicity, physical phantom, and in vivo imaging experiments. The ultralow cytotoxicity of PAA-modified nanoparticles, which is confirmed by over 80% cell viability of SH-SY5Y cells when treated by high nanoparticle concentration of 200 μg/mL, overcome the major obstacle for in vivo application. In addition, the high luminescence intensity of PAA-modified nanoparticles enables the location error of in vivo XLCT imaging less than 2 mm, which is comparable to that using commercially available bulk material Y2O3:15% Eu3+. The proposed nanoparticles promote XLCT research into an in vivo stage. Further modification of these nanoparticles with biofunctional molecules could enable the potential of targeting XLCT imaging.

Performance evaluation of the simplified spherical harmonics approximation for cone-beam X-ray luminescence computed tomography imaging

As an emerging molecular imaging modality, cone-beam X-ray luminescence computed tomography (CB-XLCT) uses X-ray-excitable probes to produce near-infrared (NIR) luminescence and then reconstructs three-dimensional (3D) distribution of the probes from surface measurements. A proper photon-transportation model is critical to accuracy of XLCT. Here, we presented a systematic comparison between the common-used Monte Carlo model and simplified spherical harmonics (SPN). The performance of the two methods was evaluated over several main spectrums using a known XLCT material. We designed both a global measurement based on the cosine similarity and a locally-averaged relative error, to quantitatively assess these methods. The results show that the SP3 could reach a good balance between the modeling accuracy and computational efficiency for all of the tested emission spectrums. Besides, the SP1 (which is equivalent to the diffusion equation (DE)) can be a reasonable alternative model for emission wavelength over 692[Formula: see text]nm. In vivo experiment further demonstrates the reconstruction performance of the SP3 and DE. This study would provide a valuable guidance for modeling the photon-transportation in CB-XLCT.

Multiple pinhole collimator based X-ray luminescence computed tomography.

X-ray luminescence computed tomography (XLCT) is an emerging hybrid imaging modality, which is able to improve the spatial resolution of optical imaging to hundreds of micrometers for deep targets by using superfine X-ray pencil beams. However, due to the low X-ray photon utilization efficiency in a single pinhole collimator based XLCT, it takes a long time to acquire measurement data. Herein, we propose a multiple pinhole collimator based XLCT, in which multiple X-ray beams are generated to scan a sample at multiple positions simultaneously. Compared with the single pinhole based XLCT, the multiple X-ray beam scanning method requires much less measurement time. Numerical simulations and phantom experiments have been performed to demonstrate the feasibility of the multiple X-ray beam scanning method. In one numerical simulation, we used four X-ray beams to scan a cylindrical object with 6 deeply embedded targets. With measurements from 6 angular projections, all 6 targets have been reconstructed successfully. In the phantom experiment, we generated two X-ray pencil beams with a collimator manufactured in-house. Two capillary targets with 0.6 mm edge-to-edge distance embedded in a cylindrical phantom have been reconstructed successfully. With the two beam scanning, we reduced the data acquisition time by 50%. From the reconstructed XLCT images, we found that the Dice similarity of targets is 85.11% and the distance error between two targets is less than 3%. We have measured the radiation dose during XLCT scan and found that the radiation dose, 1.475 mSv, is in the range of a typical CT scan. We have measured the changes of the collimated X-ray beam size and intensity at different distances from the collimator. We have also studied the effects of beam size and intensity in the reconstruction of XLCT.

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

X-ray luminescence computed tomography (XLCT) has become a promising imaging technology for biological application based on phosphor nanoparticles. There are mainly three kinds of XLCT imaging systems: pencil beam XLCT, narrow beam XLCT and cone beam XLCT. Narrow beam XLCT can be regarded as a balance between the pencil beam mode and the cone-beam mode in terms of imaging efficiency and image quality. The collimated X-ray beams are assumed to be parallel ones in the traditional narrow beam XLCT. However, we observe that the cone beam X-rays are collimated into X-ray beams with fan-shaped broadening instead of parallel ones in our prototype narrow beam XLCT. Hence we incorporate the distribution of the X-ray beams in the physical model and collected the optical data from only two perpendicular directions to further speed up the scanning time. Meanwhile we propose a depth related adaptive regularized split Bregman (DARSB) method in reconstruction. The simulation experiments show that the proposed physical model and method can achieve better results in the location error, dice coefficient, mean square error and the intensity error than the traditional split Bregman method and validate the feasibility of method. The phantom experiment can obtain the location error less than 1.1 mm and validate that the incorporation of fan-shaped X-ray beams in our model can achieve better results than the parallel X-rays.

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

Single-view x-ray luminescence computed tomography (XLCT) imaging has short data collection time that allows non-invasively and fast resolving the three-dimensional (3-D) distribution of x-ray-excitable nanophosphors within small animal in vivo. However, the single-view reconstruction suffers from a severe ill-posed problem because only one angle data is used in the reconstruction. To alleviate the ill-posedness, in this paper, we propose a wavelet-based reconstruction approach, which is achieved by applying a wavelet transformation to the acquired singe-view measurements. To evaluate the performance of the proposed method, in vivo experiment was performed based on a cone beam XLCT imaging system. The experimental results demonstrate that the proposed method cannot only use the full set of measurements produced by CCD, but also accelerate image reconstruction while preserving the spatial resolution of the reconstruction. Hence, it is suitable for dynamic XLCT imaging study.

Fast X-ray luminescence computed tomography imaging.

X-ray luminescence computed tomography (XLCT) opens new possibilities to perform molecular imaging with X-ray. However, challenges remain in dynamic XLCT imaging, where short scan time, good spatial resolution, and whole-body field of view should be considered simultaneously. In this paper, by the use of a single-view XLCT reconstruction method based on a compressive sensing (CS) technique, incorporating a cone beam XLCT imaging system, we implement fast 3-D XLCT imaging. To evaluate the performance of the method, two types of phantom experiments were performed based on a cone beam XLCT imaging system. In Case 1, one tube filled with the X-ray-excitable nanophosphor (Gd 2O 3 :Eu (3+)) was immerged in different positions in the phantom to evaluate the effect of the source position on single-view XLCT reconstruction accuracy. In Case 2, two tubes filled with Gd 2O 3 :Eu (3+) were immerged in different heights in the phantom to evaluate the whole-body imaging performance of single-view XLCT reconstruction. The experimental results indicated that the tubes used in previous phantom experiments can be resolved from single-view XCLT reconstruction images. The location error is less than 1.2 mm. In addition, since only one view data are needed to implement 3-D XLCT imaging, the acquisition time can be greatly reduced (∼1 frame/s) compared with previous XLCT systems. Hence, the technique is suited for imaging the fast distribution of the X-ray-excitable nanophosphors within a biological object.