Benchtop X-ray Fluorescence Computed Tomography Research Articles

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.

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.

Monte Carlo study of x-ray detection configurations for benchtop x-ray fluorescence computed tomography of gold nanoparticle-loaded objects

Over the last decade, the performance of benchtop x-ray fluorescence computed tomography (XFCT) systems has been significantly enhanced through hardware and software optimizations. Recent studies have indicated the need of energy-resolving pixelated/array detectors in the x-ray detection component to further improve the sensitivity and image resolution of benchtop XFCT systems while meeting the realistic constraints of dose and scan time. Thus, it is of immediate interest in the research community to conduct the following investigations: (a) delineation of strengths/weaknesses of detection configurations that incorporate pixelated/array detectors in combination with two most frequently used (parallel-hole and pinhole) collimators; (b) one-to-one comparison of their performance under identical imaging conditions of benchtop XFCT. In this study, we developed a Geant4-based Monte Carlo model to investigate the effects of the aforementioned detection configurations on the sensitivity and image resolution of a benchtop XFCT system. Using this model, we simulated the detection of x-ray fluorescence and scattered photons from gold nanoparticle-containing phantoms using energy-resolving pixelated detectors coupled with parallel-hole and pinhole collimators. Simulation results demonstrated that the detector consisting of large pixels (1 mm × 1 mm) combined with a parallel-hole collimator had better sensitivity (i.e. lower detection limit) than the detector made of smaller pixels (0.25 mm × 0.25 mm) coupled with a pinhole collimator. In comparison, although slightly less sensitive, the latter detector configuration achieved better image resolution than did the former. Thus, a detection configuration consisting of a pixelated detector with submillimeter pixels and a pinhole collimator is preferable when image resolution is critical for benchtop XFCT applications. On the other hand, the detector with larger pixels coupled with a parallel-hole collimator is better suited for benchtop XFCT applications in which higher sensitivity and shorter scan time are essential.

Quantitative Imaging of Gd Nanoparticles in Mice Using Benchtop Cone-Beam X-ray Fluorescence Computed Tomography System.

Nanoparticles (NPs) are currently under intensive research for their application in tumor diagnosis and therapy. X-ray fluorescence computed tomography (XFCT) is considered a promising non-invasive imaging technique to obtain the bio-distribution of nanoparticles which include high-Z elements (e.g., gadolinium (Gd) or gold (Au)). In the present work, a set of experiments with quantitative imaging of GdNPs in mice were performed using our benchtop XFCT device. GdNPs solution which consists of 20 mg/mL NaGdF4 was injected into a nude mouse and two tumor-bearing mice. Each mouse was then irradiated by a cone-beam X-ray source produced by a conventional X-ray tube and a linear-array photon counting detector with a single pinhole collimator was placed on one side of the beamline to record the intensity and spatial information of the X-ray fluorescent photons. The maximum likelihood iterative algorithm with scatter correction and attenuation correction method was applied for quantitative reconstruction of the XFCT images. The results show that the distribution of GdNPs in each target slice (containing liver, kidney or tumor) was well reconstructed and the concentration of GdNPs deposited in each organ was quantitatively estimated, which indicates that this benchtop XFCT system provides convenient tools for obtaining accurate concentration distribution of NPs injected into animals and has potential for imaging of nanoparticles in vivo.

A detector’s eye view (DEV)-based OSEM algorithm for benchtop x-ray fluorescence computed tomography (XFCT) image reconstruction

In this study, we developed a detector’s eye view (DEV)-based ordered subsets expectation maximization (OSEM) algorithm for more accurate reconstruction of benchtop x-ray fluorescence computed tomography (XFCT) images. The proposed approach was tested using two sets of benchtop XFCT imaging data derived from a newly performed gold nanoparticle (GNP)-containing phantom imaging study and a previously published postmortem benchtop XFCT imaging study of a tumor-bearing mouse injected with GNPs. DEV-based OSEM resulted in higher spatial resolution (up to ~20% decrease in the full width at half maximum values of the regions of interest), compared with filtered back-projection (FBP) and traditional OSEM. It also resulted in up to an order of magnitude smaller background noise in the reconstructed images than FBP, while producing consistently less background noise than traditional OSEM.

Scattering Noise Model Enhanced EM-TV Algorithm for Benchtop X-ray Fluorescence Computed Tomography Image Reconstruction

Current benchtop x-ray fluorescence computed tomography (XFCT) devices, which use x-ray tubes to stimulate x-ray fluorescence (XRF) photons, suffer from the contamination of Compton scatter background produced by the polychromatic incident beam. The conventional maximum-likelihood expectation-maximization (ML-EM) algorithm only considers the noise model of the XRF signal, which results in high statistical noise in reconstructed images caused by scattered photons. In this study, we proposed a scattering noise model enhanced EM-TV algorithm for benchtop XFCT image reconstruction in order to reduce the noise of scatter background and improve the sensitivity of XFCT images. The statistical noise of scattered photons was considered in the likelihood function and the EM iteration step was modified correspondingly to suppress the statistical noise caused by Compton scattered photons. The robustness of the EM iteration was improved by applying the reweighted total variation (TV) norm as the penalty function. Numerical simulations and imaging experiments of a PMMA phantom consisting of gadolinium (Gd) solutions were performed to validate the proposed algorithm. The phantom was irradiated by a cone-beam polychromatic source and the projection was recorded by a linear-array photon counting detector. For comparison, the XFCT images of Gd were reconstructed using different algorithms. Results indicate that compared with the conventional ML-EM algorithm, the proposed algorithm can obtain XFCT images with lower background noise and higher contrast, which may further improve the sensitivity and image performance of current benchtop XFCT systems.

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

BackgroundX-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.PurposeTo validate the performance of a Geant4-based Monte Carlo (MC) model of a benchtop multi-pinhole XFCT system for quantitative imaging of GNPs.MethodsThe 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.ResultsThe 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.ConclusionThe 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.

A Monte Carlo Model of a Benchtop X-Ray Fluorescence Computed Tomography System and Its Application to Validate a Deconvolution-Based X-Ray Fluorescence Signal Extraction Method.

In this study, we developed and validated a Geant4-based Monte Carlo (MC) model of an experimental benchtop X-ray fluorescence (XRF) computed tomography (XFCT) system for quantitative imaging of metallic nanoparticles such as gold nanoparticles (GNPs) injected into small animals for preclinical testing of various NP-based diagnostic and therapeutic approaches. Detailed hardware components of the current benchtop XFCT system, including the X-ray source, excitation beam collimation and filtration, custom imaging phantoms with GNP solutions, and single/ring/linear array detectors with custom collimation, were incorporated into the MC model. In conjunction with a known CdTe detector response function, a deconvolution-based XRF signal extraction method was also developed in this study, which enabled complete separation of gold K-shell XRF peaks even when they almost overlapped and facilitated extraction of XRF signals from a broadband Compton scattered photon background. The extracted signal-to-background ratios were comparable with those expected using an ideal detector with high enough energy resolution (e.g., 0.1 keV full-width at half-maximum). Once convoluted with the CdTe detector response function, the MC-calculated spectra for excitation beams or emitted photons and XFCT image spatial resolutions agreed well with those measured experimentally. Thus, the current MC model can be used to optimize the beam/imaging parameters (e.g., beam geometry, excitation X-ray beam energy, and X-ray filter material) as well as the design of critical hardware components (e.g., detector collimators) within the current benchtop XFCT system. Also, the current XRF signal extraction method can relax the usual stringent requirement of detector energy resolution while not degrading the sensitivity of benchtop XFCT.

WE‐H‐206‐01: Photoacoustic Tomography: Multiscale Imaging From Organelles to Patients by Ultrasonically Beating the Optical Diffusion Limit

Lihong V. Wang: Photoacoustic tomography (PAT), combining non‐ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x‐rays do. Consequently, high‐resolution pure optical imaging (e.g., confocal microscopy, two‐photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffers from both poor contrast in early‐stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high‐resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole‐body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label‐free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PATBenjamin M. W. Tsui: Multi‐modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi‐modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi‐pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high‐resolution and artifact‐free MPH and sparse‐view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub‐millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state‐of‐art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi‐modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi‐modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi‐modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi‐modality imaging instrumentation and techniques that are being developed.Sang Hyun Cho; X‐ray fluorescence (XRF) imaging, such as x‐ray fluorescence computed tomography (XFCT), offers unique capabilities for accurate identification and quantification of metals within the imaging objects. As a result, it has emerged as a promising quantitative imaging modality in recent years, especially in conjunction with metal‐based imaging probes. This talk will familiarize the audience with the basic principles of XRF/XFCT imaging. It will also cover the latest development of benchtop XFCT technology. Additionally, the use of metallic nanoparticles such as gold nanoparticles, in conjunction with benchtop XFCT, will be discussed within the context of preclinical multimodal multiplexed molecular imaging. Learning Objectives: To learn the basic principles of XRF/XFCT imaging To learn the latest advances in benchtop XFCT development for preclinical imagingFunding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; L. Wang, Funding Support: NIH; COI: Microphotoacoustics; S. Cho, Yes:;NIH/NCI grant R01CA155446 DOD/PCRP grant W81XWH‐12‐1‐0198

WE‐H‐206‐00: Advances in Preclinical Imaging

Lihong V. Wang: Photoacoustic tomography (PAT), combining non‐ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x‐rays do. Consequently, high‐resolution pure optical imaging (e.g., confocal microscopy, two‐photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffers from both poor contrast in early‐stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high‐resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole‐body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label‐free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PATBenjamin M. W. Tsui: Multi‐modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi‐modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi‐pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high‐resolution and artifact‐free MPH and sparse‐view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub‐millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state‐of‐art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi‐modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi‐modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi‐modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi‐modality imaging instrumentation and techniques that are being developed.Sang Hyun Cho; X‐ray fluorescence (XRF) imaging, such as x‐ray fluorescence computed tomography (XFCT), offers unique capabilities for accurate identification and quantification of metals within the imaging objects. As a result, it has emerged as a promising quantitative imaging modality in recent years, especially in conjunction with metal‐based imaging probes. This talk will familiarize the audience with the basic principles of XRF/XFCT imaging. It will also cover the latest development of benchtop XFCT technology. Additionally, the use of metallic nanoparticles such as gold nanoparticles, in conjunction with benchtop XFCT, will be discussed within the context of preclinical multimodal multiplexed molecular imaging. Learning Objectives: To learn the basic principles of XRF/XFCT imaging To learn the latest advances in benchtop XFCT development for preclinical imagingFunding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; L. Wang, Funding Support: NIH; COI: Microphotoacoustics; S. Cho, Yes:;NIH/NCI grant R01CA155446 DOD/PCRP grant W81XWH‐12‐1‐0198

WE‐H‐206‐02: Recent Advances in Multi‐Modality Molecular Imaging of Small Animals

Lihong V. Wang: Photoacoustic tomography (PAT), combining non‐ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x‐rays do. Consequently, high‐resolution pure optical imaging (e.g., confocal microscopy, two‐photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffers from both poor contrast in early‐stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high‐resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole‐body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label‐free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PATBenjamin M. W. Tsui: Multi‐modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi‐modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi‐pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high‐resolution and artifact‐free MPH and sparse‐view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub‐millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state‐of‐art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi‐modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi‐modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi‐modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi‐modality imaging instrumentation and techniques that are being developed.Sang Hyun Cho; X‐ray fluorescence (XRF) imaging, such as x‐ray fluorescence computed tomography (XFCT), offers unique capabilities for accurate identification and quantification of metals within the imaging objects. As a result, it has emerged as a promising quantitative imaging modality in recent years, especially in conjunction with metal‐based imaging probes. This talk will familiarize the audience with the basic principles of XRF/XFCT imaging. It will also cover the latest development of benchtop XFCT technology. Additionally, the use of metallic nanoparticles such as gold nanoparticles, in conjunction with benchtop XFCT, will be discussed within the context of preclinical multimodal multiplexed molecular imaging. Learning Objectives: To learn the basic principles of XRF/XFCT imaging To learn the latest advances in benchtop XFCT development for preclinical imagingFunding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; L. Wang, Funding Support: NIH; COI: Microphotoacoustics; S. Cho, Yes:;NIH/NCI grant R01CA155446 DOD/PCRP grant W81XWH‐12‐1‐0198

Improving x‐ray fluorescence signal for benchtop polychromatic cone‐beam x‐ray fluorescence computed tomography by incident x‐ray spectrum optimization: A Monte Carlo study

To develop an accurate and comprehensive Monte Carlo (MC) model of an experimental benchtop polychromatic cone-beam x-ray fluorescence computed tomography (XFCT) setup and apply this MC model to optimize incident x-ray spectrum for improving production/detection of x-ray fluorescence photons from gold nanoparticles (GNPs). A detailed MC model, based on an experimental XFCT system, was created using the Monte Carlo N-Particle (MCNP) transport code. The model was validated by comparing MC results including x-ray fluorescence (XRF) and scatter photon spectra with measured data obtained under identical conditions using 105 kVp cone-beam x-rays filtered by either 1 mm of lead (Pb) or 0.9 mm of tin (Sn). After validation, the model was used to investigate the effects of additional filtration of the incident beam with Pb and Sn. Supplementary incident x-ray spectra, representing heavier filtration (Pb: 2 and 3 mm; Sn: 1, 2, and 3 mm) were computationally generated and used with the model to obtain XRF/scatter spectra. Quasimonochromatic incident x-ray spectra (81, 85, 90, 95, and 100 keV with 10 keV full width at half maximum) were also investigated to determine the ideal energy for distinguishing gold XRF signal from the scatter background. Fluorescence signal-to-dose ratio (FSDR) and fluorescence-normalized scan time (FNST) were used as metrics to assess results. Calculated XRF/scatter spectra for 1-mm Pb and 0.9-mm Sn filters matched (r ≥ 0.996) experimental measurements. Calculated spectra representing additional filtration for both filter materials showed that the spectral hardening improved the FSDR at the expense of requiring a much longer FNST. In general, using Sn instead of Pb, at a given filter thickness, allowed an increase of up to 20% in FSDR, more prominent gold XRF peaks, and up to an order of magnitude decrease in FNST. Simulations using quasimonochromatic spectra suggested that increasing source x-ray energy, in the investigated range of 81-100 keV, increased the FSDR up to a factor of 20, compared to 1 mm Pb, and further facilitated separation of gold XRF peaks from the scatter background. A detailed MC model of an experimental benchtop XFCT system has been developed and validated. In exemplary calculations to illustrate the usefulness of this model, it was shown that potential use of quasimonochromatic spectra or judicious choice of filter material/thickness to tailor the spectrum of a polychromatic x-ray source can significantly improve the performance of benchtop XFCT, while considering trade-offs between FSDR and FNST. As demonstrated, the current MC model is a reliable and powerful computational tool that can greatly expedite the further development of a benchtop XFCT system for routine preclinical molecular imaging with GNPs and other metal probes.

TH-A-141-06: Optimization of Incident X-Ray Source Spectrum Through Filtration for a Benchtop X-Ray Fluorescence Computed Tomography (XFCT) System

Purpose: To optimize acquisition of fluorescence photon signal from gold nanoparticles (GNPs) and reduce the effect of Compton scatter in benchtop x-ray fluorescence computed tomography (XFCT). Methods: In polychromatic XFCT, fluorescence signal is obscured by Compton scatter of source photons, and thus the choice of source spectrum is crucial. An experimental XFCT system for irradiation of a GNP-containing small animal-sized phantom was accurately modeled using the MCNP5 code for Monte Carlo simulations. The model used either a lead (Pb) or tin (Sn) filter to harden the 105 kVp source spectrum, and was validated with fluorescence/scatter profile measurements. Spectra (Pb: 1, 2, and 3 mm; Sn: 0.9, 1, 2, and 3 mm) were input into the model and their effect on fluorescence production/detection was investigated. Simulations were also run with hypothetical quasi-monochromatic x-ray sources (81, 85, 90, 95, and 100 keV) to determine the ideal energy for discriminating gold K-shell fluorescence peaks from Compton scatter background. Fluorescence signal-to-dose ratio (FSDR) and relative scan time (RST) were used to assess the degree of optimization during simulations. Results: For both materials, increasing filtration hardened source spectra and significantly decreased fluence available for producing fluorescence photons, while increasing FSDR. The RST increased at a much higher rate for a given increase in FSDR. Compared to Pb, Sn produced generally higher overall fluence, more prominent fluorescence peaks, favorably harder scatter profiles, increased FSDR, and shorter RST. Simulations using hypothetical quasi-monochromatic spectra showed that increasing source energy, between 81 and 100 keV, increased signal-to-background ratio and FSDR. Conclusion: Judicious choice of filter material/thickness to tailor polychromatic x-ray spectrum, considering trade-offs between FSDR and RST, can dramatically improve the performance of benchtop XFCT. This work will foster the further development of a benchtop XFCT system for routine pre-clinical imaging applications with GNPs.Supported by NIH/NCI grant R01CA155446; NIH/NCI grant R01CA155446

Experimental demonstration of benchtop x-ray fluorescence computed tomography (XFCT) of gold nanoparticle-loaded objects using lead- and tin-filtered polychromatic cone-beams

This report presents the first experimental demonstration, to our knowledge, of benchtop polychromatic cone-beam x-ray fluorescence computed tomography (XFCT) for a simultaneous determination of the spatial distribution and amount of gold nanoparticles (GNPs) within small-animal-sized objects. The current benchtop experimental setup successfully produced XFCT images accurately showing the regions containing small amount of GNPs (on the order of 0.1 mg) within a 3 cm diameter plastic phantom. In particular, the performance of the current XFCT setup was improved remarkably (e.g., at least a factor of 3 reduction in XFCT scan time) using a tin-filtered polychromatic beam in comparison with a lead-filtered beam. The results of this study strongly suggest that the current benchtop XFCT configuration can be made practical with a few modifications such as the deployment of array detectors, while meeting realistic constraints on x-ray dose, scan time and image resolution for routine pre-clinical in vivo imaging with GNPs.

X-ray fluorescence computed tomography (XFCT) imaging of gold nanoparticle-loaded objects using 110 kVp x-rays

A conventional x-ray fluorescence computed tomography (XFCT) technique requires monochromatic synchrotron x-rays to simultaneously determine the spatial distribution and concentration of various elements such as metals in a sample. However, the synchrotron-based XFCT technique appears to be unsuitable for in vivo imaging under a typical laboratory setting. In this study we demonstrated, for the first time to our knowledge, the possibility of performing XFCT imaging of a small animal-sized object containing gold nanoparticles (GNPs) at relatively low concentrations using polychromatic diagnostic energy range x-rays. Specifically, we created a phantom made of polymethyl methacrylate plastic containing two cylindrical columns filled with saline solution at 1 and 2 wt% GNPs, respectively, mimicking tumors/organs within a small animal. XFCT scanning of the phantom was then performed using microfocus 110 kVp x-ray beam and cadmium telluride (CdTe) x-ray detector under a pencil beam geometry after proper filtering of the x-ray beam and collimation of the detector. The reconstructed images clearly identified the locations of the two GNP-filled columns with different contrast levels directly proportional to gold concentration levels. On the other hand, the current pencil-beam implementation of XFCT is not yet practical for routine in vivo imaging tasks with GNPs, especially in terms of scanning time. Nevertheless, with the use of multiple detectors and a limited number of projections, it may still be used to image some objects smaller than the current phantom size. The current investigation suggests several modification strategies of the current XFCT setup, such as the adoption of the quasi-monochromatic cone/fan x-ray beam and XFCT-specific spatial filters or pinhole detector collimators, in order to establish the ultimate feasibility of a bench-top XFCT system for GNP-based preclinical molecular imaging applications.