Nanobeam X-ray fluorescence and diffraction computed tomography on human bone with a resolution better than 120 nm.

Studying nanostructured hierarchical materials such as the biomineralized bone is challenging due to their complex 3D structures that call for high spatial resolution. One route to study such materials is X-ray powder diffraction computed tomography (XRD-CT) that reveals the 3D distribution of crystalline phases and X-ray fluorescence computed tomography (XRF-CT) that provides element distributions. However, the spatial resolution of XRD-CT has thus far been limited. Here we demonstrate better than 120 nm 3D resolution on human bone in XRD-CT and XRF-CT measured simultaneously using X-ray nanobeams. The results pave the way for nanoscale 3D characterization of nanocrystalline composites like bone at unprecedented detail.

Investigation of transmission computed tomography (CT) image quality and x-ray dose achievable from an experimental dual-mode benchtop x-ray fluorescence CT and transmission CT system.

OBJECTIVE: To investigate the image quality and x-ray dose associated with a transmission computed tomography (CT) component implemented within the same platform of an experimental benchtop x-ray fluorescence CT (XFCT) system for multimodal preclinical imaging applications. METHODS: Cone-beam CT scans were performed using an experimental benchtop CT + XFCT system and a cylindrically-shaped 3D-printed polymethyl methacrylate phantom (3 cm in diameter, 7 cm in height) loaded with various concentrations (0.05-1 wt. %) of gold nanoparticles (GNPs). Two commercial CT quality assurance phantoms containing 3D line-pair (LP) targets and contrast targets were also scanned. The x-ray beams of 40 and 62 kVp, both filtered by 0.08 mm Cu and 0.4 mm Al, were used with 17 ms of exposure time per projection at three current settings (2.5, 5, and 10 mA). The ordered-subset simultaneous algebraic reconstruction and total variation-minimization methods were used to reconstruct images. Sparse projection and short scan were considered to reduce the x-ray dose. The contrast-to-noise ratio (CNR) and modulation transfer function (MTF) were calculated. RESULTS: The lowest detectable concentration of GNPs (CNR > 5) and the highest spatial resolution (per MTF50%) were 0.10 wt. % and 9.5 LP/CM, respectively, based on the images reconstructed from 360 projections of the 40 kVp beam (or x-ray dose of 3.44 cGy). The background noise for the image resulting in the lowest GNP detection limit was 25 Hounsfield units. CONCLUSION: The transmission CT component within the current experimental benchtop CT + XFCT system produced images deemed acceptable for multimodal (CT + XFCT) imaging purposes, with less than 4 cGy of x-ray dose.

High-sensitivity and spatial resolution benchtop cone beam XFCT imaging system with pixelated photon counting detectors using enhanced multipixel events correction method.

Objective.High atomic number element nanoparticles have shown potential in tumor diagnosis and therapy. X-ray fluorescence computed tomography (XFCT) technology enables quantitative imaging of high atomic number elements by specifically detecting characteristic x-ray signals. The potential for further biomedical applications of XFCT depends on balancing sensitivity, spatial resolution, and imaging speed in existing XFCT imaging systems.Approach.In this study, we utilized a high-energy resolution pixelated photon-counting detector for XFCT imaging. We tackled degradation caused by multi-pixel events in the photon-counting detector through energy and interaction position corrections. Sensitivity and spatial resolution imaging experiments were conducted using PMMA phantoms to validate the effectiveness of the multi-pixel events correction algorithm.Main results.After correction, the system's sensitivity and spatial resolution have both improved. Furthermore, XFCT/CBCT dual-modality imaging of gadolinium nanoparticles within mice subcutaneous tumor was successfully achieved.Significance.These results demonstrate the preclinical research application potential of the XFCT/CBCT dual-modality imaging system in high atomic number nanoparticle-based tumor diagnosis and therapy.

Contrast-to-noise ratio comparison between X-ray fluorescence emission tomography and computed tomography.

Purpose: We provide a comparison of X-ray fluorescence emission tomography (XFET) and computed tomography (CT) for detecting low concentrations of gold nanoparticles (GNPs) in soft tissue and characterize the conditions under which XFET outperforms energy-integrating CT (EICT) and photon-counting CT (PCCT). Approach: We compared dose-matched Monte Carlo XFET simulations and analytical fan-beam EICT and PCCT simulations. Each modality was used to image a numerical mouse phantom and contrast-depth phantom containing GNPs ranging from 0.05% to 4% by weight in soft tissue. Contrast-to-noise ratios (CNRs) of gold regions were compared among the three modalities, and XFET's detection limit was quantified based on the Rose criterion. A partial field-of-view (FOV) image was acquired for the phantom region containing 0.05% GNPs. Results: For the mouse phantom, XFET produced superior CNR values ( CNRs = 24.5 , 21.6, and 3.4) compared with CT images obtained with both energy-integrating ( CNR = 4.4 , 4.6, and 1.5) and photon-counting ( CNR = 6.5 , 7.7, and 2.0) detection systems. More generally, XFET outperformed CT for superficial imaging depths ( < 28.75 mm ) for gold concentrations at and above 0.5%. XFET's surface detection limit was quantified as 0.44% for an average phantom dose of 16 mGy compatible with in vivo imaging. XFET's ability to image partial FOVs was demonstrated, and 0.05% gold was easily detected with an estimated dose of ∼ 81.6 cGy to a localized region of interest. Conclusions: We demonstrate a proof of XFET's benefit for imaging low concentrations of gold at superficial depths and the feasibility of XFET for in vivo metal mapping in preclinical imaging tasks.

Full-fieldin vivoimaging of nanoparticles using benchtop cone-beam XFCT system with pixelated photon counting detector.

Objective.X-ray fluorescence computed tomography (XFCT) is a promising noninvasive technique forin vivoimaging of high-Z elements (e.g. gadolinium (Gd) or gold (Au)). In this study we upgraded our experimental XFCT system using a flat panel photon counting detector with redesigned pinhole collimation in order to achieve 3D XFCT images during one scan.Approach.Aiming at the characteristics of pinhole-collimated cone-beam XFCT imaging, a new scatter correction algorithm was proposed to estimate the normalized spectrum of scatter background based on K-N formula and realize correction by a weighted least squares method. Then, images were quantitatively reconstructed by a maximum likelihood iterative algorithm with the attenuation correction.Main results.The potential on full-fieldin vivoXFCT imaging of this new system was investigated. An imaging experiment of a PMMA phantom with the diameter of 35 mm was carried out for quantitative evaluation of the system performance. Results show that 2 mg ml-1Gd solutions can be successfully reconstructed with a 45 min cone-beam XFCT scan.In vivoXFCT imaging experiments of mice with injection of Gd nanoparticles (GdNPs) were also performed and demonstrated in this paper. A mouse was injected through the tail vein with 20 mg ml-1NaGdF4 solution and then anesthetized with isoflurane during the cone-beam XFCT scan.Significance.The distribution of the GdNPs inside the mouse can be well reconstructed so that the deposition of NPsin vivocan be clearly observed, which indicates the feasibility of the proposed system for full-field XFCT of small animals and further potential in relevantin vivoresearch.

Use of the Fully Spectroscopic Pixelated Cadmium Telluride Detector for Benchtop X-Ray Fluorescence Computed Tomography.

In this work, we integrated a commercially-available fully-spectroscopic pixelated cadmium telluride (CdTe) detector system as a two-dimensional (2D) array detector into our existing benchtop cone-beam x-ray fluorescence computed tomography (XFCT) system. After integrating this detector, known as High-Energy X-ray Imaging Technology (HEXITEC), we performed quantitative imaging of gold nanoparticle (GNP) distribution in a small animal-sized phantom using our benchtop XFCT system. Owing to the upgraded detector component within our benchtop XFCT system, we were able to conduct this phantom imaging in an unprecedented manner by volumetric XFCT scans followed by XFCT image reconstruction in 3D. The current results showed that adoption of HEXITEC, in conjunction with a custom-made parallel-hole collimator, drastically reduced the XFCT scan time/dose. Compared with the previous work performed with our original benchtop XFCT system adopting a single crystal CdTe detector, the currently observed reduction was up to a factor of 5, while achieving comparable GNP detection limit under similar experimental conditions. Overall, we demonstrated, for the first time to the best our knowledge, the feasibility of benchtop XFCT imaging of small animal-sized objects containing biologically relevant GNP concentrations (on the order of 0.1 mg Au/cm3 or 100 parts-per-million/ppm), with the scan time (on the order of 1 minute)/x-ray dose (on the order of 10 cGy) that are likely meeting the minimum requirements for routine preclinical imaging applications.

Characterization of a Pixelated Cadmium Telluride Detector System Using a Polychromatic X-Ray Source and Gold Nanoparticle-Loaded Phantoms for Benchtop X-Ray Fluorescence Imaging.

Pixelated semi-conductor detectors providing high energy resolution enable parallel acquisition of x-ray fluorescence (XRF) signals, potentially leading to performance enhancement of benchtop XRF imaging or computed tomography (XFCT) systems utilizing ordinary polychromatic x-ray sources. However, little is currently known about the characteristics of such detectors under typical operating conditions of benchtop XRF imaging/XFCT. In this work, a commercially available pixelated cadmium telluride (CdTe) detector system, HEXITEC (High Energy X-ray Imaging Technology), was characterized to address this issue. Specifically, HEXITEC was deployed into our benchtop cone-beam XFCT system, and used to detect gold Kα XRF photons from gold nanoparticle (GNP)-loaded phantoms. To facilitate the detection of XRF photons, various parallel-hole stainless steel collimators were fabricated and coupled with HEXITEC. A pixel-by-pixel spectrum merging algorithm was introduced to obtain well-defined XRF + scatter spectra with parallel-hole collimators. The effect of charge sharing addition (CSA) and discrimination (CSD) algorithms was also investigated for pixel-level CS correction. Finally, the detector energy resolution, in terms of the full-width at half-maximum (FWHM) values at two gold Kα XRF peaks (~68 keV), was also determined. Under the current experimental conditions, CSD provided the best energy resolution of HEXITEC (~1.05 keV FWHM), compared with CSA and no CS correction. This FWHM value was larger (by up to ~0.35 keV) than those reported previously for HEXITEC (at ~60 keV Am-241 peak) and single-crystal CdTe detectors (at two gold Kα XRF peaks). This investigation highlighted characteristics of HEXITEC as well as the necessity for application-specific detector characterization.

Technical Note: A benchtop cone-beam x-ray fluorescence computed tomography (XFCT) system with a high-power x-ray source and transmission CT imaging capability.

PURPOSE: This report describes upgrades and performance characterization of an experimental benchtop cone-beam x-ray fluorescence computed tomography (XFCT) system capable of determining the spatial distribution and concentration of metal probes such as gold nanoparticles (GNPs). Specifically, a high-power (~3 kW) industrial x-ray source and transmission CT capability were deployed in the same platform under the cone-beam geometry. METHODS: All components of the system are described in detail, including the x-ray source, imaging stage, cadmium-telluride detector for XFCT, and flat-panel detector for transmission CT imaging. The general data acquisition scheme for XFCT and transmission CT is also explicated. The detection limit of the system was determined using calibration samples containing water and GNPs at various concentrations. Samples were then embedded in a small-animal-sized phantom and imaged with XFCT and CT. The reconstructed XFCT and CT images were compared and analyzed using the contrast-to-noise ratio for each GNP-containing region of interest. Also, measurements of the incident beam spectra used for XFCT and CT imaging were made and the corresponding x-ray dose rates were estimated, along with the imaging dose. RESULTS: The present configuration produced a GNP detection limit of 0.03 wt. % with the delivery of an effective dose of 1.87 cGy per projection. XFCT scan of an animal-sized phantom containing low concentrations (down to 0.03 wt. %) of GNP-loaded inserts can be performed within an hour. CONCLUSIONS: The high performance of the system combined with the ability to perform transmission CT in tandem with XFCT suggests that the currently developed benchtop cone-beam XFCT/CT system, in conjunction with GNPs, can be used for routine multimodal preclinical imaging tasks with less stringent dose constraints such as ex vivo imaging. With further effort to minimize XFCT imaging dose as discussed in this report, it may also be used for in vivo imaging.

A Geant4-based Monte Carlo study of a benchtop multi-pinhole X-ray fluorescence computed tomography imaging.

BACKGROUND: X-ray fluorescence (XRF) computed tomography (XFCT) has shown promise for molecular imaging of metal nanoparticles such as gold nanoparticles (GNPs) and benchtop XFCT is under active development due to its easy access, low-cost instrumentation and operation. PURPOSE: To validate the performance of a Geant4-based Monte Carlo (MC) model of a benchtop multi-pinhole XFCT system for quantitative imaging of GNPs. METHODS: The MC mode consisted of a fan-beam x-ray source (125 kVp), which was used to stimulate the emission of XRF from the GNPs, a phantom (3 cm in diameter) which included six or nine inserts (3 mm in diameter), each of which contained the same (1 wt. %) or various (0.08-1 wt. %) concentrations of GNPs, a multi-pinhole collimator which could acquire multiple projections simultaneously and a one-sided or two-sided two-dimensional (2D) detector. Various pinhole diameters (3.7, 2, 1, 0.5 and 0.25 mm) and various particle numbers (20, 40, 80 and 100 billion) were simulated and the results for single pinhole and multi-pinhole (9 pinholes) imaging were compared. RESULTS: The image resolution for a 1 mm multi-pinhole was between 0.88 and 1.38 mm. The detection limit for multi-pinhole operation was about 0.09 wt. %, while that for the single pinhole was about 0.13 wt. %. For a fixed number of pinholes, noise increased with decreasing number of photons. CONCLUSION: The MC mode could acquire 2D slice images of the object without rotation and demonstrated that a multi-pinhole XFCT imaging system could be a potential bioimaging modality for nanomedical applications.