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

X-ray fluorescence computed tomography (XFCT) is a technique that can identify, quantify, and locate elements within objects by detecting x-ray fluorescence (characteristic x-rays) stimulated by an excitation source, typically derived from a synchrotron. However, the use of a synchrotron limits practicality and accessibility of XFCT for routine biomedical imaging applications. Therefore, we have developed the ability to perform XFCT on a benchtop setting with ordinary polychromatic x-ray sources. Here, we report our postmortem study that demonstrates the use of benchtop XFCT to accurately image the distribution of gold nanoparticles (GNPs) injected into a tumor-bearing mouse. The distribution of GNPs as determined by benchtop XFCT was validated using inductively coupled plasma mass spectrometry. This investigation shows drastically enhanced sensitivity and specificity of GNP detection and quantification with benchtop XFCT, up to two orders of magnitude better than conventional x-ray CT. The results also reaffirm the unique capabilities of benchtop XFCT for simultaneous determination of the spatial distribution and concentration of nonradioactive metallic probes, such as GNPs, within the context of small animal imaging. Overall, this investigation identifies a clear path toward in vivo molecular imaging using benchtop XFCT techniques in conjunction with GNPs and other metallic probes.

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) is a quantitative imaging technique which detects the characteristic x-ray fluorescent (XRF) photons emitted from the target element in the object. XFCT experiments were first performed using synchrotron as the incident beam in order to obtain the XRF signal with high intensity and low scattering background. However, consider that the synchrotron will not be soon used for clinical application due to its limited access, researchers focus more on the benchtop XFCT system with conventional polychromatic source in recent years. Recent XFCT experiments aimed at small animals mainly use iodine (I), barium (Ba), gadolinium (Gd) or gold (Au) as the contrast agent. In this paper, we reported our latest in-vivo imaging study using our benchtop XFCT device with conventional cone-beam x-ray source and a linear-array photon counting detector. About 0.35 ml Gd nanoparticles (GdNPs) solution which consists of 2% NaGdF4 was injected into a nude mouse (weighted 20 g). 45 projections were obtained for image reconstruction with scanning time set at 10s per angle. The results show that the distribution of GdNPs in the mouse were well reconstructed. The benchtop XFCT device presented in this work has the capacity to obtain the bio-distribution of GdNPs, which may be helpful in relevant nanoparticle research.

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

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.

This work is aimed at evaluating the image reconstruction techniques used in single photon emission computed tomography (SPECT/CT) imaging. The reconstruction techniques considered in this work are: the ordered subset expectation maximization (OSEM) and the Filtered Back Projection (FBP). An anthropomorphic torso phantom with lung and liver inserts was injected with 99mTc. The liver and the background were given 0.2 MBq/ml and 0.07 MBq/ml respectively. The lungs inserts were filled with polystyrene beads for humanization. A mimicked 30 ml tumor (27 mm) in the liver insert was given 2 MBq/ml sequential SPECT/CT (step and shot, 10 mins over 180° per head) and CT (120 kVp, 80 mAs) projections were acquired using dual head SPECT/16 slice CT system. The projections were reconstructed using OSEM (10 subsets for 2–10 numbers of iterations, Butterworth post filtering, 10 orders and 0.48 frequencies) and FBP (using Butterworth post filtering at 10 order and cutoff frequencies of 0.38–0.58, 0.05 gaps). Image J software was used for the image analysis. Statistical t-test tested the mean gray values of the tumor and its background. The OSEM and FBP reconstructed images were evaluated from their contrast-to-noise ratio (CNR). The optimal parameter was selected based on 3–5 CNR detection range set by the Rose criterion. The t-test showed the background and the tumors mean values to be statistically significant (P ≪ 0.05). The CNR values for FBP images were all below the detection range, maximum value at the cutoff frequency 0.48 (1.69). In OSEM images at cutoff frequency 0.48, the CNR values were within the detection range for 2–8 numbers of iteration with maximum value (4.89) at 4 numbers of iteration. OSEM was found to be the best for tumor detection and administered activity can be reduced at 4 OSEM’s of iterations (40 MLEM iterations) for patient safety. Keywords: Anthropomorphic torso phantom, 99mTc, SPECT, iterative reconstruction, CNR, P-Value, liver Cite this Article F. Usman, R. Zainon, A. Saidu, A. Bala. Evaluation of image reconstruction techniques in Single photon emission computed tomography (SPECT/CT) imaging. Research & Reviews: Journal of Physics. 2016; 5(2): 13–22p.

Objective To study the effect of the reconstruction method on the semi-quantitative distribution of dopamine transporter (DAT) in the brain, 2β-carbomethoxy-3β-(4-fluorophe-nyl)-(N-11C-methyl)tropane (11C-CFT) PET images of healthy subjects were reconstructed by different PET reconstruction methods. Methods From March 2014 to June 2015, the 11C-CFT PET images of 41 healthy subjects were reconstructed by filtering back projection(FBP) method and ordered subsets expectation maximization (OSEM) iterative method. The brain regions of interest (ROI), namely, caudate nucleus, anterior putamen, and posterior shell nucleus, were automatically sketched with the parietal and occipital cortex lacking of DAT distribution as reference regions. The semi-quantitative value of DAT distribution was calculated using the following formula: radioactivity count of ROI/radioactivity count of parietal and occipital cortex-1. Paired t-test was used to compare the semi-quantitative values of DAT distribution. Correlation analysis was performed using the Pearson correlation analysis. Results The values of DAT distribution based on OSEM were as follows: caudate nucleus (1.77-2.15), anterior putamen (2.17-2.39), and posterior putamen (1.71-2.06). The values of DAT distribution based on FBP were as follows: caudate nucleus (1.68-2.10), anterior putamen (2.07-2.37), and posterior putamen (1.62-1.96). In the bilateral caudate nucleus and anterior and posterior putamen, the 11C-CFT of DAT distribution by OSEM was significantly higher than that by FBP(t=9.658-15.859, all P=0.000). The Pearson correlation analysis showed that the semi-quantitative values of DAT distribution by FBP and OSEM were positively correlated with each other in the bilateral caudate nucleus and anterior and posterior putamen (R2=0.907-0.951, all P=0.000). The DAT distribution by OSEM and FBP decreased with aging in the caudate nucleus and anterior and posterior putamen. Conclusions A significant difference was found in the semi-quantitative value of the DAT distribution in the brain of healthy subjects by different PET reconstruction methods. Therefore, a consistent PET image reconstruction method should be used in a multicenter or longitudinal study. Key words: Dopamine plasma membrane transport proteins; Positron-emission tomography; Filtered backprojection; Iterative

Purpose: To examine the feasibility of quantifying concentration and spatial distribution of gold nanoparticles (GNPs) present within a small animal‐sized object by applying an x‐ray fluorescence computed tomography (XFCT) technique with a bench‐top, polychromatic, cone‐beam x‐ray source. Method and Materials: The Monte Carlo code MCNP5 was used to simulate the acquisition of gold fluorescence photons under a polychromatic cone‐beam XFCT scenario. Three 1 cm‐diameter columns containing saline solution with GNPs (≤ 2% gold by weight) were inserted into a 5 cm‐diameter cylindrical PMMA phantom. The phantom was irradiated by a 110 kVp x‐ray source, and the resulting gold fluorescence and Compton‐scattered photons were collected by a series of 11 energy‐sensitive tallies. A maximized‐likelihood iterative reconstruction algorithm was implemented to reconstruct the image of GNP distribution. The effects of attenuation of both the primary beam through the phantom and the gold fluorescence photons en route to the detector were corrected during the image reconstruction. The attenuation map of the phantom was known a priori, although it could have been easily measured with a transmission scan. Results: An accurate image of the GNP‐containing phantom was successfully reconstructed, with both spatial distribution and relative concentration of GNPs well defined. The pixel intensity of regions containing GNPs was linearly proportional to gold concentration, which would allow XFCT technique to quantify the GNP concentration and spatial distribution of an unknown sample. Conclusion: This study shows the feasibility of performing XFCT imaging using a bench‐top, polychromatic, cone‐beam x‐ray source. The current approach would make XFCT imaging accessible to applications where a synchrotron‐based XFCT imaging may be inapplicable, such as in vivo measurements of GNP biodistribution.

A recent study investigated the feasibility to develop a bench-top x-ray fluorescence computed tomography (XFCT) system capable of determining the spatial distribution and concentration of gold nanoparticles (GNPs) in vivo using a diagnostic energy range polychromatic (i.e. 110 kVp) pencil-beam source. In this follow-up study, we examined the feasibility of a polychromatic cone-beam implementation of XFCT by Monte Carlo (MC) simulations using the MCNP5 code. In the current MC model, cylindrical columns with various sizes (5–10 mm in diameter) containing water loaded with GNPs (0.1–2% gold by weight) were inserted into a 5 cm diameter cylindrical polymethyl methacrylate phantom. The phantom was then irradiated by a lead-filtered 110 kVp x-ray source, and the resulting gold fluorescence and Compton-scattered photons were collected by a series of energy-sensitive tallies after passing through lead parallel-hole collimators. A maximum-likelihood iterative reconstruction algorithm was implemented to reconstruct the image of GNP-loaded objects within the phantom. The effects of attenuation of both the primary beam through the phantom and the gold fluorescence photons en route to the detector were corrected during the image reconstruction. Accurate images of the GNP-containing phantom were successfully reconstructed for three different phantom configurations, with both spatial distribution and relative concentration of GNPs well identified. The pixel intensity of regions containing GNPs was linearly proportional to the gold concentration. The current MC study strongly suggests the possibility of developing a bench-top, polychromatic, cone-beam XFCT system for in vivo imaging.

BackgroundPositron Emission Tomography (PET), Computed Tomography (CT), PET/CT and Single Photon Emission Tomography (SPECT) are non-invasive imaging tools used for creating two dimensional (2D) cross section images of three dimensional (3D) objects. PET and SPECT have the potential of providing functional or biochemical information by measuring distribution and kinetics of radiolabelled molecules, whereas CT visualizes X-ray density in tissues in the body. PET/CT provides fused images representing both functional and anatomical information with better precision in localization than PET alone.Images generated by these types of techniques are generally noisy, thereby impairing the imaging potential and affecting the precision in quantitative values derived from the images. It is crucial to explore and understand the properties of noise in these imaging techniques. Here we used autocorrelation function (ACF) specifically to describe noise correlation and its non-isotropic behaviour in experimentally generated images of PET, CT, PET/CT and SPECT.MethodsExperiments were performed using phantoms with different shapes. In PET and PET/CT studies, data were acquired in 2D acquisition mode and reconstructed by both analytical filter back projection (FBP) and iterative, ordered subsets expectation maximisation (OSEM) methods. In the PET/CT studies, different magnitudes of X-ray dose in the transmission were employed by using different mA settings for the X-ray tube. In the CT studies, data were acquired using different slice thickness with and without applied dose reduction function and the images were reconstructed by FBP. SPECT studies were performed in 2D, reconstructed using FBP and OSEM, using post 3D filtering. ACF images were generated from the primary images, and profiles across the ACF images were used to describe the noise correlation in different directions. The variance of noise across the images was visualised as images and with profiles across these images.ResultsThe most important finding was that the pattern of noise correlation is rotation symmetric or isotropic, independent of object shape in PET and PET/CT images reconstructed using the iterative method. This is, however, not the case in FBP images when the shape of phantom is not circular. Also CT images reconstructed using FBP show the same non-isotropic pattern independent of slice thickness and utilization of care dose function. SPECT images show an isotropic correlation of the noise independent of object shape or applied reconstruction algorithm. Noise in PET/CT images was identical independent of the applied X-ray dose in the transmission part (CT), indicating that the noise from transmission with the applied doses does not propagate into the PET images showing that the noise from the emission part is dominant. The results indicate that in human studies it is possible to utilize a low dose in transmission part while maintaining the noise behaviour and the quality of the images.ConclusionThe combined effect of noise correlation for asymmetric objects and a varying noise variance across the image field significantly complicates the interpretation of the images when statistical methods are used, such as with statistical estimates of precision in average values, use of statistical parametric mapping methods and principal component analysis. Hence it is recommended that iterative reconstruction methods are used for such applications. However, it is possible to calculate the noise analytically in images reconstructed by FBP, while it is not possible to do the same calculation in images reconstructed by iterative methods. Therefore for performing statistical methods of analysis which depend on knowing the noise, FBP would be preferred.

The Siemens Biograph TruePoint TrueV (B-TPTV) positron emission tomography (PET) scanner performs 3D PET reconstruction using a system matrix with point spread function (PSF) modeling (called the True X reconstruction). PET resolution was dramatically improved with the True X method. In this study, we assessed the spatial resolution and image quality on a B-TPTV PET scanner. In addition, we assessed the feasibility of animal imaging with a B-TPTV PET and compared it with a microPET R4 scanner. Spatial resolution was measured at center and at 8 cm offset from the center in transverse plane with warm background activity. True X, ordered subset expectation maximization (OSEM) without PSF modeling, and filtered back-projection (FBP) reconstruction methods were used. Percent contrast (% contrast) and percent background variability (% BV) were assessed according to NEMA NU2-2007. The recovery coefficient (RC), non-uniformity, spill-over ratio (SOR), and PET imaging of the Micro Deluxe Phantom were assessed to compare image quality of B-TPTV PET with that of the microPET R4. When True X reconstruction was used, spatial resolution was <3.65 mm with warm background activity. % contrast and % BV with True X reconstruction were higher than those with the OSEM reconstruction algorithm without PSF modeling. In addition, the RC with True X reconstruction was higher than that with the FBP method and the OSEM without PSF modeling method on the microPET R4. The non-uniformity with True X reconstruction was higher than that with FBP and OSEM without PSF modeling on microPET R4. SOR with True X reconstruction was better than that with FBP or OSEM without PSF modeling on the microPET R4. This study assessed the performance of the True X reconstruction. Spatial resolution with True X reconstruction was improved by 45 % and its % contrast was significantly improved compared to those with the conventional OSEM without PSF modeling reconstruction algorithm. The noise level was higher than that with the other reconstruction algorithm. Therefore, True X reconstruction should be used with caution when quantifying PET data.

In pelvic bone SPECT using Tc-99m labeled compounds, physical effects such as nonhomogeneous attenuation and the accumulation of activity into the bladder during the data acquisition process can often result in data inconsistencies. With filtered backprojection (FBP) reconstruction, this may result in streak artifacts. Various methods for attenuation compensation can be employed to account for some of these streaks, but if the rate of uptake of tracer in to the bladder is sufficient, the resultant streaks may be significant enough to impair lesion detection. We have investigated various reconstruction methods in an effort to reduce these artifacts. In order to assess the impact of inconsistent bladder activities on the detection of pelvic lesions, SPECT imaging was simulated using the Zubal voxelized phantom, for cases of both a static bladder activity and a changing activity distribution. Reconstructions were performed using FBP, ordered subset-expectation maximization (OSEM) and dynamic expectation maximization (dEM) and was assessed for lesion detectability using a channelized, nonprewhitening (CNPW) numerical observer model. This observer model was used to optimize reconstruction strategies for a human LROC observer study. The human LROC observer study was performed in order to assess the various reconstruction methods in terms of lesion detectability. Three human observers were used in this test. The results of this test indicate that FBP performs significantly worse than static OSEM iterative reconstruction with attenuation correction when assessed using the area under the LROC curve (maximal ALROC=0.47 for FBP versus 0.71 for OSEM). Visually, the dEM algorithm produces images with slightly reduced streak artifacts compared to OSEM, but this improvement was not reflected in significantly improved ALROC values. In fact, when assessed using human LROC methodology, detectability actually decreased slightly when using dEM (maximal ALROC=0.71 for OSEM versus 0.66 for dEM), although this reduction was not determined to be statistically significant. It is possible that the slightly reduced performance of the dEM algorithm may be due, in part, to not performing an optimization in the number of reconstruction iterations as was performed for the OSEM method

Purpose: To demonstrate the feasibility of determining the location and gold concentration of gold nanoparticle (GNP)‐loaded regions within polymethyl methacrylate (PMMA) phantoms using cone‐beam polychromatic x‐ray fluorescence computed tomography (XFCT) technique. Methods: Tubes containing water and GNPs at 2%, 1%, and 0.5% by weight were inserted into two 5 cm‐long cylindrical PMMA phantoms with 3 cm and 5 cm in diameter, respectively. The phantoms were irradiated by a cone‐beam of polychromatic 110 kVp x‐rays filtered by 1.0 mm of lead. Energy‐sensitive cadmium telluride detectors behind a 2.5 mm diameter lead pinhole collimator collected the spectrum of emitted gold K‐shell fluorescence and Compton scattered photons at an angle of 90° relative to the beam central axis as the phantom was rotated to a series of 60 projection angles in 6° steps. Sinograms of gold fluorescence photon signals were constructed by extracting the gold fluorescence peak height from the Compton background, and the image of GNP location and concentration was reconstructed using a maximum likelihood iterative reconstruction algorithm. Results: Using the measured sinograms, images of GNP location were successfully reconstructed for both the 3 cm and 5 cm phantoms. Additionally, the signal intensity was linearly related to gold concentration. The x‐ray dose delivered during the XFCT scanning was measured using the TG‐61 protocol, and it was determined that, using an array detector, it would be possible to acquire these images with roughly 30 cGy of x‐ray dose delivered. Conclusions: This study demonstrates, for the first time to our knowledge, the feasibility of imaging GNP location and concentration within small animal‐sized objects using an ordinary cone‐beam polychromatic x‐ray source under realistic constraints on dose and scan time. This investigation strongly suggests a bench‐top XFCT system will ultimately become a viable option for in‐vivo molecular imaging with conjugated or unconjugated GNPs.

X-ray fluorescence computed tomography (XFCT), which is considered as a promising approach to determine the bio-distribution of high Z elements such as gadolinium (Gd) and gold (Au), is carried out more on the benchtop XFCT systems with polychromatic x-rays produced by x-ray tubes in recent years, which means that the XRF signal stimulated by the polychromatic x-ray source is strongly affected by the Comptonscattered photons. In order to reduce the dose of the scattered photons with energies near the energy of the fluorescent photons, filters made of lead (Pb), copper (Cu), aluminum (Al), tungsten (W) or tin (Sn) were used in previous studies. However, using filters will reduce the intensity of the incident beam, which causes larger statistical noises. In addition, the energy response of the detector will weaken the effect of filtering, which also causes the decrease of signal quality. In this paper, a set of simulations were carried out to investigate the signal-to-noise ratio (SNR) of the projection data detected by a CZT photon counting detector array in a benchtop fan-beam XFCT system. The phantom is stimulated by a polychro matic X-ray source filtered by different filters made of Pb, W, Sn, Cu, and Al. Simulations show that due to the statistical noises and the energy response of CZT linear array detector, optimizing the incident X-ray spectrum using common filters doesn’t help improving the SNR of the projection data at a fixed power of x-ray tube.

X-ray fluorescence computed tomography (XFCT) is a synchrotron-based imaging modality employed for mapping the distribution of elements within slices or volumes of intact specimens. A pencil beam of external radiation is used to stimulate emission of characteristic X-rays from within a sample, which is scanned and rotated through the pencil beam in a first-generation tomographic geometry. The measurements so obtained can be represented as generalizations of the attenuated Radon Transform. The range of angular scanning employed is the subject of some variability in the XFCT imaging community, as some groups rotate the object through a full 360deg, while others employ only a 180deg rotation. In both cases, the entire object is scanned through the beam at each projection view. The use of a 180deg rotation is sometimes justified by implicit reference to a well-known symmetry property of the Radon transform, but that symmetry does not hold for the attenuated Radon transform. In this work, we demonstrate that a full scan of the object at each view coupled with a 360deg rotation does contain a two-fold data redundancy. While the redundancy does not give rise to a simple symmetry condition as in the case of the Radon transform, we will show that it does indeed license the use of 180deg scheme. However, we will also demonstrate that when there is a single external fluorescence detector, the redundancy also licenses a potentially more attractive reduced-scan scheme, in which the object is rotated through a full 360deg, but in which only the half of the object closest to the fluorescence detector is scanned at each projection view. This new scheme may permit both reduced imaging times and improved image quality.