X-ray Fluorescence Computed Tomography Research Articles

A High-Sensitivity Benchtop X-Ray Fluorescence Emission Tomography (XFET) System With a Full-Ring of X-Ray Imaging-Spectrometers and a Compound-Eye Collimation Aperture.

The advent of metal-based drugs and metal nanoparticles as therapeutic agents in anti-tumor treatment has motivated the advancement of X-ray fluorescence computed tomography (XFCT) techniques. An XFCT imaging modality can detect, quantify, and image the biodistribution of metal elements using the X-ray fluorescence signal emitted upon X-ray irradiation. However, the majority of XFCT imaging systems and instrumentation developed so far rely on a single or a small number of detectors. This work introduces the first full-ring benchtop X-ray fluorescence emission tomography (XFET) system equipped with 24 solid-state detectors arranged in a hexagonal geometry and a 96-pinhole compound-eye collimator. We experimentally demonstrate the system's sensitivity and its capability of multi-element detection and quantification by performing imaging studies on an animal-sized phantom. In our preliminary studies, the phantom was irradiated with a pencil beam of X-rays produced using a low-powered polychromatic X-ray source (90kVp and 60W max power). This investigation shows a significant enhancement in the detection limit of gadolinium to as low as 0.1 mg/mL concentration. The results also illustrate the unique capabilities of the XFET system to simultaneously determine the spatial distribution and accurately quantify the concentrations of multiple metal elements.

Iterative nanoparticle bioengineering enabled by x-ray fluorescence imaging.

Nanoparticles (NPs) are currently developed for drug delivery and molecular imaging. However, they often get intercepted before reaching their target, leading to low targeting efficacy and signal-to-noise ratio. They tend to accumulate in organs like lungs, liver, kidneys, and spleen. The remedy is to iteratively engineer NP surface properties and administration strategies, presently a time-consuming process that includes organ dissection at different time points. To improve this, we propose a rapid iterative approach using whole-animal x-ray fluorescence (XRF) imaging to systematically evaluate NP distribution in vivo. We applied this method to molybdenum-based NPs and clodronate liposomes for tumor targeting with transient macrophage depletion, leading to reduced accumulations in lungs and liver and eventual tumor detection. XRF computed tomography (XFCT) provided 3D insight into NP distribution within the tumor. We validated the results using a multiscale imaging approach with dye-doped NPs and gene expression analysis for nanotoxicological profiling. XRF imaging holds potential for advancing therapeutics and diagnostics in preclinical pharmacokinetic studies.

Unveiling breast cancer metastasis through an advanced X-ray imaging approach

Breast cancer is a significant global health burden, causing a substantial number of deaths. Systemic metastatic tumour cell dissemination is a major cause of poor outcomes. Understanding the mechanisms underlying metastasis is crucial for effective interventions. Changes in the extracellular matrix play a pivotal role in breast cancer metastasis. In this work, we present an advanced multimodal X-ray computed tomography, by combining Small-angle X-ray Scattering Tensor Tomography (SAXS-TT) and X-ray Fluorescence Computed Tomography (XRF-CT). This approach likely brings out valuable information about the breast cancer metastasis cascade. Initial results from its application on a breast cancer specimen reveal the collective influence of key molecules in the metastatic mechanism, identifying a strong correlation between zinc accumulation (associated with matrix metalloproteinases MMPs) and highly oriented collagen. MMPs trigger collagen alignment, facilitating breast cancer cell intravasation, while iron accumulation, linked to angiogenesis and vascular endothelial growth factor VEGF, supports cell proliferation and metastasis. Therefore, these findings highlight the potential of the advanced multimodal X-ray computed tomography approach and pave the way for in-depth investigation of breast cancer metastasis, which may guide the development of novel therapeutic approaches and enable personalised treatment strategies, ultimately improving patient outcomes in breast cancer management.

First Demonstration of Compton Camera Used for X-Ray Fluorescence Imaging.

X-ray fluorescence computed tomography (XFCT) is a promising approach used for obtaining the distribution of high-Z elements in the target object. The characteristic energy of X-ray fluorescence (XRF) photons makes XFCT have higher sensitivity and contrast ratio. Conventional XFCT systems usually require mechanical collimators, which leads to a huge loss of incident photons and reduce photon collection efficiency. The Compton camera is an imaging modality that uses electronic collimation to obtain the incident direction of the photons, which brings advantages in the detection area and X-ray photon collection efficiency. Compton cameras can also achieve three-dimensional (3D) imaging with one or several views of scanning without rotation. Therefore, it is a good idea to realize XRF imaging by using Compton cameras, which may provide more potential applications and imaging possibilities, such as handheld XRF imaging or image-guided interventional operation. In this work, we demonstrate the first Compton camera platform which is used for XRF imaging. The proposed X-ray fluorescence Compton camera (XFCC) mainly consists of a conventional X-ray tube (150kVp) and a Timepix3 photon-counting detector (PCD). A PMMA phantom with insertions containing different concentrations of 4%, 6%, 8%, and 10% (weight/volume) Gd solution is scanned by a fan-beam X-ray. Besides, a Compton camera-based X-ray fluorescence imaging reconstruction method (CCFIRM) is developed to solve specific problems in XFCC reconstruction. The reconstruction images and the quantitative analyses of the contrast-to-noise ratio (CNR) are presented. The results indicate that the detectability limit of the proposed XFCC platform is 3.5139 wt.% (CNR =4 ).

Characterization of a polychromatic microfocus X-ray fluorescence imaging setup with metallic contrast agents in a microphysiological tumor model

Introduction: Accurate diagnosis and personalized treatments involving site-targeted cancer localization, drug delivery, therapeutic strategy, and disease pathways identification, rely on a precise understanding of biomarker kinetics, drug pharmacokinetics, and mechanistic behaviour of functionalized tracers through in vitro and in vivo studies. X-ray fluorescence (XRF) computed tomography (XFCT) offers a potential alternative to current 3D imaging techniques for spatiotemporal localization of nanoparticle-tracers with high spatial resolution and sensitivity. In this work, the applicability of a benchtop cone-beam system with a polychromatic X-ray source was examined with regard to physical constraints of engineered tissue models.Methods: A tissue engineering approach based on a decellularized scaffold was used to establish a 3D breast cancer model with MDA-MB-231 cells in co-culture with primary human fibroblasts. The 3D breast cancer system, in combination with small-animal-sized phantoms, was used to demonstrate the novel integrated pre-clinical imaging approach to perform in vitro surrogate investigations and non-destructive analysis on biophantoms. These models are adopted to evaluate the functionality and optimize the setup for high-spatial-resolution, fast, and fully-3D quantitative imaging. Polychromatic X-rays from a microfocus source are used for XRF stimulation from conventional Gadolinium (Gd) and nanoparticle-based Molybdenum (MoNPs) contrast agents.Results and Discussion: The intestinal scaffold allowed the invasion of the breast cancer cells over this barrier and therefore provides a valuable tool to study metastasis formation of tumor cells from epithelial origin. The breast cancer model was well suited for the development and validation of the proposed XRF imaging, with spatial resolution under <2 mm and contrast dose in the order of a few 100 μg/mL (∼0.3 mg/mL for Gd and ∼0.5 mg/mL for MoNPs), radiation dose in the order of a few 100 cGy (280 cGy for Gd and 94 cGy for MoNPs, with a possible reduction of an order of magnitude for Gd and 67% for MoNPs), and imaging time in the order of 10 min for Gd (33 min total) and 100 min (2.8 h total) for MoNPs, approaching in vivo conform conditions for pre-clinical studies. High-resolution XFCT for tissue-engineered cancer models would be of significant interest in biomedical research and diagnostic imaging, e.g., for an increased mechanistic understanding of molecular processes in tumor formation or early cancer detection.

Feasibility Simulation of 3D Benchtop Multi-Pinhole X-ray Fluorescence Computed Tomography with Two Novel Geometries

In this work, we developed and validated two novel imaging geometries of benchtop multi-pinhole X-ray fluorescence computed tomography (XFCT) systems with Geant4 Toolkit. One of the Monte Carlo (MC) models utilized a fan beam source to illuminate a single slice of the object, a detector and a multi-pinhole collimator to image each slice’s X-ray fluorescence (XRF). The other model consisted of a cone-beam X-ray source (designed as a 5 mm wide fan beam to reduce simulation time) to scan the whole object, two detectors and two multi-pinhole collimators to image the emissions. The phantom used in the simulations included four sections, each with three cone-shaped gold nanoparticle (GNP) inserts (5 mm in height, 3 mm in diameter across the top) with center-to-center distances of 4 mm, 4.5 mm and 4.86 mm. The GNPs concentration was 0.1 wt. %, 0.3 wt. %, 0.5 wt. % and 0.7 wt. %, respectively. The diameter of the multi-pinhole collimator was 1 mm. Performance was evaluated for pinhole-detector-distance (PDD) of 5 cm, 3.5 cm and 2.5 cm, and the results for different object layers and for single pinhole and multi-pinhole (9 pinholes) imaging were compared. The data showed that results worsened with decreasing GNPs insert diameters and with decreasing PDD (object-pinhole-distance was fixed). The multi-pinhole configurations performed better than a single pinhole. The detection limit for the first multi-pinhole operation was 0.21 wt. %; the second was 0.24 wt. %. Detection limits for the single pinhole were 0.32 wt. % and 0.35 wt. %, respectively. The first MC model could acquire 2D slice images of the object without rotation and the second MC model could image the 3D object efficiently. These two novel multi-pinhole systems could potentially provide a bioimaging modality for nanomedical applications.

Full-field in vivo imaging 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 for in vivo imaging 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-field in vivo XFCT 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−1 Gd solutions can be successfully reconstructed with a 45 min cone-beam XFCT scan. In vivo XFCT 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−1 NaGdF4 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 NPs in vivo can be clearly observed, which indicates the feasibility of the proposed system for full-field XFCT of small animals and further potential in relevant in vivo research.

XFCT-MRI hybrid multimodal contrast agents for complementary imaging.

Multimodal contrast agents in biomedical imaging enable the collection of more comprehensive diagnostic information. In the present work, we design hybrid ruthenium-decorated superparamagnetic iron oxide nanoparticles (NPs) as the contrast agents for both magnetic resonance imaging (MRI) and X-ray fluorescence computed tomography (XFCT). The NPs are synthesized via a one-pot polyol hot injection route, in diethylene glycol. In vivo preclinical studies demonstrate the possibility of correlative bioimaging with these contrast agents. The complementarity allows accurate localization, provided by the high contrast of the soft tissues in MRI combined with the elemental selectivity of XFCT, leading to NP detection with high specificity and resolution. We envision that this multimodal imaging could find future applications for early tumor diagnosis, improved long-term treatment monitoring, and enhanced radiotherapy planning.

Numerical and Monte Carlo Simulation for Polychromatic L-shell X-ray Fluorescence Computed Tomography Based on Pinhole Collimator with Sheet-Beam Geometry

X-ray fluorescence computed tomography (XFCT) has attracted wide attention due to its ability to simultaneously and nondestructively obtain structural and elemental distribution information within samples. In this paper, we presented an image system based on the pinhole collimator for the polychromatic L-shell XFCT to reduce time consumption and improve the detection limit. First, the imaging system model was expressed by formulas and discretized. Then, two phantoms (A and B) were scanned by numerical simulation and Monte Carlo simulation. Both phantoms with the same diameter (10 mm) and height (10 mm) were cylinders filled with PMMA, and embedded with GNP-loaded cylinders. The phantom A was inserted by six 1.5 mm-diameter cylinders with different Au concentrations ranging from 0.2% to 1.2%. The phantom B was inserted by eight cylinders with the same Au concentration (1%), but a radius ranging from 0.1 mm to 0.8 mm. Finally, the reconstruction of the XFCT images was performed using the method with and without absorption correction, respectively. The feasibility of XFCT system presented in this paper was demonstrated by the numerical simulation and the Monte Carlo simulation. The results show that absorption attenuation can be corrected by the presented method, and the contrast to noise ratio (CNR) is proportional to Au concentration but almost remains unchanged with the radius of GNP-loaded cylinders, which may provide the necessary justification for further optimization of the imaging system.

Reduction of Compton Background Noise for X-ray Fluorescence Computed Tomography with Deep Learning

For bench-top X-ray fluorescence computed tomography (XFCT), the X-ray tube source will bring extreme Compton background noise, resulting in a low signal-to-noise ratio and low contrast detection limit. In this paper, a noise2noise denoising algorithm based on the UNet deep learning network is proposed. The network can use noise image learning to convert the noise image into a clean image. Two sets of phantoms (high concentration Gd phantom and low concentration Bi phantom) are used for scanning to simulate the imaging process under different noise levels and generate the required data set. Additionally, the data set is generated by Geant4 simulation. In the training process, the L1 loss function is used for its good convergence. The image quality is evaluated according to CNR and pixel profile, which shows that our algorithm is better than BM3D, both visually and quantitatively.

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.

High energy synchrotron X-ray fluorescence trace element study of a millimeter-sized asteroidal particle in preparation for the Hayabusa2 return sample analyses

The trace element content and distribution - including rare Earth elements (REEs) - measured in mm-sized asteroidal samples returned by JAXA's Hayabusa2 mission are important chemical parameters to decipher asteroid Ryugu's chronology of formation linked to early Solar System processes. In order to identify and analyze ancient Solar Nebula components, such as calcium‑aluminum-rich inclusions (CAIs), by their trace element and REE content, a synchrotron beam with an incident energy of 90 keV is used to optimize the XRF signal and increase the information depth in the sample. The application of a (sub-)microscopic X-ray beam with such a high excitation energy not only allows for the detection of a wide range of heavy elements, but also to study their 3-dimensional distribution in mm-sized samples by means of X-ray fluorescence computed tomography (XRF-CT). The experiment was performed in anticipation of the initial analysis of the Hayabusa2 return samples at beamline ID15a of the European Synchrotron Radiation Facility (ESRF), Grenoble, France. The samples were analyzed with a focused beam of 0.5 × 0.5 μm2, achieving limit of detection values as low as 0.5 ppm with an acquisition time of 1 s. Here we present results of scanning XRF(-CT) analysis of a mm-sized sample of the Murchison meteorite, a Mighei type chondrite (CM2), wherein a 9.6 × 11.5 × 8.2 μm3 CAI phase was detected and analyzed. The CAI grain is shown to be detectable throughout the entire sample volume (~700 μm) during an XRF-CT scan over a full 360° angular range, thus proving the applicability of the method to study the microscopic distribution of high-Z elements at trace level concentration within millimeter-sized asteroidal particles.

Identification of the Calcium, Aluminum, and Magnesium Distribution within Millimeter-Sized Extraterrestrial Materials Using Nonresonant X-ray Raman Spectroscopy in Preparation for the Hayabusa2 Sample Return Mission.

The nondestructive investigation of millimeter-sized meteoritic materials is often hindered by self-absorption effects. Using X-ray-based analytical methods, the information depth for many elements (Z < 30) is in the range of up to only a few hundred micrometers, and for low-Z elements (Z < 20), this is reduced even further to only a few tens of micrometers. However, the investigation of these low-Z elements, in particular calcium, aluminum, and magnesium, is of great importance to planetary geologists and cosmochemists, as these elements are regularly used to characterize and identify specific features of interest in extraterrestrial materials, especially primitive chondritic material. In this work, nonresonant inelastic X-ray scattering from core electrons was performed at beamline ID20 of the ESRF in a direct tomography approach in order to visualize these low-Z elements within the millimeter-sized meteoritic samples. The obtained 3D elemental distribution volumes were compared to results from X-ray fluorescence-CT and absorption CT experiments and were found to be in good agreement. Additionally, several regions of interest could be identified within the inelastic scattering volumes, containing information that is not available through the other presented means. As such, the proposed approach presents a valuable tool for the nondestructive investigation of low-Z elemental distributions within millimeter-sized extraterrestrial materials, such as the samples of the Hayabusa2 sample return mission.

Prostate Cancer Targeted X-Ray Fluorescence Imaging via Gold Nanoparticles Functionalized With Prostate-Specific Membrane Antigen (PSMA).

The gold nanoparticle (GNP) as a promising theranostic probe has been increasingly studied. The tumor-targeting efficiency of GNPs is crucial to increase the therapeutic ratio. In this study, we developed PSMA-targeted GNPs to enhance GNP uptake in prostate cancer and developed an x-ray fluorescence imaging system to noninvasively monitor and assess GNP delivery. For targeted therapy of prostate cancer, anti-prostate-specific membrane antigen (PSMA) antibodies were conjugated onto PEGylated GNPs through 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) (EDC/NHS) chemistry. In vivo imaging was implemented using an in-house-developed dual-modality computed tomography (CT) and x-ray fluorescence CT (XFCT) system on mice bearing subcutaneous LNCaP prostate tumors. After intravenous administration of GNPs (15 mg/mL, 200 μL), the x-ray fluorescence signals from the tumor were collected at various time points (5 minutes to approximately 30 hours) for GNP pharmacokinetics analysis. At 24 hours after administration, x-ray fluorescence projection (XRFproj) and XFCT imaging were conducted to evaluate the prostate tumor uptake of active- and passive-targeting GNPs. Inductively coupled plasma mass spectrometry analysis was adopted as a benchmark to verify the quantification accuracy of XRFproj/XFCT imaging. Fluorescence microscopic imaging confirmed the enhanced (approximately 4 times) targeting efficiency of PSMA-targeted GNPs in vitro. The pharmacokinetics analysis showed enhanced tumor uptake/retention of PSMA-targeted GNPs and revealed that the peak tumor accumulation appeared at approximately 24 hours after intravenous administration. Both XRFproj and XFCT imaging presented their accuracy in quantifying GNPs within tumors noninvasively. Moreover, XFCT imaging verified its unique capabilities to simultaneously determine the heterogeneous spatial distribution and the concentration of GNPs within tumors in vivo. In conjunction with PSMA-targeted GNPs, XRFproj/XFCT would be a highly sensitive tool for targeted imaging of prostate cancer, benefiting the elucidation of mechanisms of GNP-assisted prostate-cancer therapy.

Carbon Quantum Dots Conjugated Rhodium Nanoparticles as Hybrid Multimodal Contrast Agents.

Nanoparticle (NP)-based contrast agents enabling different imaging modalities are sought for non-invasive bio-diagnostics. A hybrid material, combining optical and X-ray fluorescence is presented as a bioimaging contrast agent. Core NPs based on metallic rhodium (Rh) have been demonstrated to be potential X-ray Fluorescence Computed Tomography (XFCT) contrast agents. Microwave-assisted hydrothermal method is used for NP synthesis, yielding large-scale NPs within a significantly short reaction time. Rh NP synthesis is performed by using a custom designed sugar ligand (LODAN), constituting a strong reducing agent in aqueous solution, which yields NPs with primary amines as surface functional groups. The amino groups on Rh NPs are used to directly conjugate excitation-independent nitrogen-doped carbon quantum dots (CQDs), which are synthesized through citrate pyrolysis in ammonia solution. CQDs provided the Rh NPs with optical fluorescence properties and improved their biocompatibility, as demonstrated in vitro by Real-Time Cell Analysis (RTCA) on a macrophage cell line (RAW 264.7). The multimodal characteristics of the hybrid NPs are confirmed with confocal microscopy, and X-ray Fluorescence (XRF) phantom experiments.

Simulation Research of Potential Contrast Agents for X-Ray Fluorescence CT with Photon Counting Detectors

XFCT is a novel method for the early cancer detection. Increasing concentration of contrast agents and incident X-rays’ energy were used to improve detecting accuracy, which greatly increased the prevalence of contrast-induced nephropathy. Therefore, this research explores the adaptive contrast agents and uses Geant4 to simulate the imaging conditions of Pt, Bi, Gd, Ru, and Au for searching the lowest detectable concentration based on the fast multi-pinhole collimated XFCT (fmpc-XFCT) imaging system and low incident energy. Several imaging parameters including pinhole radius (0.7, 0.8, and 1 mm) were adjusted, and the optimized EM-TV algorithm was used to reconstruct XFCT images. It is found that Bi element is superior to other metal elements in terms of the contrast-to-noise ratio (CNR) and fluorescence efficiency, and the lowest concentration that can be detected is 0.12% with optimal parameters.

X-ray Fluorescence Computed Tomography (XFCT) Imaging with a Superfine Pencil Beam X-ray Source

X-ray fluorescence computed tomography (XFCT) is a molecular imaging technique that can be used to sense different elements or nanoparticle (NP) agents inside deep samples or tissues. However, XFCT has not been a popular molecular imaging tool because it has limited molecular sensitivity and spatial resolution. We present a benchtop XFCT imaging system in which a superfine pencil-beam X-ray source and a ring of X-ray spectrometers were simulated using GATE (Geant4 Application for Tomographic Emission) Monte Carlo software. An accelerated majorization minimization (MM) algorithm with an L1 regularization scheme was used to reconstruct the XFCT image of molybdenum (Mo) NP targets. Good target localization was achieved with a DICE coefficient of 88.737%. The reconstructed signal of the targets was found to be proportional to the target concentrations if detector number, detector placement, and angular projection number are optimized. The MM algorithm performance was compared with the maximum likelihood expectation maximization (ML-EM) and filtered back projection (FBP) algorithms. Our results indicate that the MM algorithm is superior to the ML-EM and FBP algorithms. We found that the MM algorithm was able to reconstruct XFCT targets as small as 0.25 mm in diameter. We also found that measurements with three angular projections and a 20-detector ring are enough to reconstruct the XFCT images.

Self-Absorption Correction in X-Ray Fluorescence- Computed Tomography With Deep Convolutional Neural Network

Data collected from the X-ray fluorescence-computed tomography (XFCT) is frequently reconstructed with algorithms proposed for X-ray transmission tomography. As these algorithms do not model the self-absorption effect inherent to XFCT, their capacity on accurately reconstructing the elemental distribution is limited. Although algorithms specialized for XFCT reconstruction have been developed, the majority of them impose strict requirements on the samples and the acquisition setup. To relax these prerequisites, a deep convolutional neural network is proposed to correct the self-absorption effect in the sinogram domain. Through quantitative evaluation, we conclude that the well-trained neural network can correct fluorescence sinograms affected by the self-absorption effect. Furthermore, we demonstrate that such corrections enable conventional algorithms to reconstruct the elemental distribution with high fidelity. As the only input required by the proposed neural network is the fluorescence sinogram, it is fully automatic and is applicable to different scan setups and samples.

Gold nanoparticle detection and quantification in therapeutic MV beams via pair production

Purpose. We propose a new detection method of gold nanoparticles (AuNP) in therapeutic megavoltage (MV) x-ray beams by means of coincidence counting of annihilation photons following pair production in gold. Methods. The proposed MV x-ray induced positron emission (MVIPE) imaging technique is studied by radiation transport computations using MCNP6 (3D) and CEPXS/ONEDANT (1D) codes for two water phantoms: a 35 cm slab and a similarly sized cylinder, both having a 5 cm AuNP filled region in the center. MVIPE is compared to the standard x-ray fluorescence computed tomography (XFCT). MVIPE adopts MV x-ray sources (Co-60, 2 MV, 6 MV, 6 MV with closed MLC and 15 MV) and relies on the detection of 511 keV photon-pairs. XFCT uses kilovoltage sources (100 kVp, 120 kVp and 150 kVp) and imaging is characterized by analysis of k α1,2 Au characteristic lines. Three levels of AuNP concentration were studied: 0.1%, 1% and 10% by weight. Results. Annihilation photons in the MVIPE technique originate both in the AuNP and in water along the x-ray beam path with significantly larger production in the AuNP-loaded region. MVIPE signal from AuNP is linearly increasing with AuNP concentration up to 10%wt, while XFCT signal reaches saturation due to self-absorption within AuNP. The production of annihilation photons is proportional to the MV source energy. MVIPE technique using a 15 MV pencil beam and 10 wt% AuNP detects about 4.5 × 103 511 keV-photons cm−2 at 90° w/r to the incident beam per 109 source photons cm−2; 500 of these come from AuNP. In contrast, the XFCT technique using 150 kVp detects only about 100 k α1-photons cm−2 per 109 source photons cm−2. Conclusions. In MVIPE, the number of annihilation photons produced for different MV-beam energies and AuNP concentrations is significantly greater than the k α1 photons generated in XFCT. Coincidence counting in MVIPE allows to avoid collimation, which is a major limiting factor in XFCT. MVIPE challenges include the filtering of Compton scatter and annihilation photons originating in water.

Optical and X-ray Fluorescent Nanoparticles for Dual Mode Bioimaging.

Nanoparticle (NP) based contrast agents detectable via different imaging modalities (multimodal properties) provide a promising strategy for noninvasive diagnostics. Core–shell NPs combining optical and X-ray fluorescence properties as bioimaging contrast agents are presented. NPs developed earlier for X-ray fluorescence computed tomography (XFCT), based on ceramic molybdenum oxide (MoO2) and metallic rhodium (Rh) and ruthenium (Ru), are coated with a silica (SiO2) shell, using ethanolamine as the catalyst. The SiO2 coating method introduced here is demonstrated to be applicable to both metallic and ceramic NPs. Furthermore, a fluorophore (Cy5.5 dye) was conjugated to the SiO2 layer, without altering the morphological and size characteristics of the hybrid NPs, rendering them with optical fluorescence properties. The improved biocompatibility of the SiO2 coated NPs without and with Cy5.5 is demonstrated in vitro by Real-Time Cell Analysis (RTCA) on a macrophage cell line (RAW 264.7). The multimodal characteristics of the core–shell NPs are confirmed with confocal microscopy, allowing the intracellular localization of these NPs in vitro to be tracked and studied. In situ XFCT successfully showed the possibility of in vivo multiplexed bioimaging for multitargeting studies with minimum radiation dose. Combined optical and X-ray fluorescence properties empower these NPs as effective macroscopic and microscopic imaging tools.