Spillover Ratios Research Articles

Comparison of Imaging Characteristics of (124)I PET for Determination of Optimal Energy Window on the Siemens Inveon PET.

Purpose. 124I has a half-life of 4.2 days, which makes it suitable for imaging over several days over its uptake and washout phases. However, it has a low positron branching ratio (23%), because of prompt gamma coincidence due to high-energy γ-photons (602 to 1,691 keV), which are emitted in cascade with positrons. Methods. In this study, we investigated the optimal PET energy window for 124I PET based on image characteristics of reconstructed PET. Image characteristics such as nonuniformities, recovery coefficients (RCs), and the spillover ratios (SORs) of 124I were measured as described in NEMA NU 4-2008 standards. Results. The maximum and minimum prompt gamma coincidence fraction (PGF) were 33% and 2% in 350~800 and 400~590 keV, respectively. The difference between best and worst uniformity in the various energy windows was less than 1%. The lowest SORs of 124I were obtained at 350~750 keV in nonradioactive water compartment. Conclusion. Optimal energy window should be determined based on image characteristics. Our developed correction method would be useful for the correction of high-energy prompt gamma photon in 124I PET. In terms of the image quality of 124I PET, our findings indicate that an energy window of 350~750 keV would be optimal.

Performance evaluation of the small-animal PET scanner ClairvivoPET using NEMA NU 4-2008 Standards

The aim of this study was to evaluate the performance of ClairvivoPET using NEMA NU4 standards.The ClairvivoPET incorporates a LYSO dual depth-of-interaction detector system with 151 mm axial field of view (FOV). Spatial resolution, sensitivity, counting rate capabilities, and image quality were evaluated using NEMA NU4-2008 standards. Normal mouse imaging was also performed for 10min after intravenous injection of 18F(-)-NaF. Data were compared with 19 other preclinical PET scanners.Spatial resolution measured using full width at half maximum on FBP-ramp reconstructed images was 2.16 mm at radial offset 5 mm of the axial centre FOV. The maximum absolute sensitivity for a point source at the FOV centre was 8.72%. Peak noise equivalent counting rate (NECR) was 415kcps at 14.6MBq ml−1. The uniformity with the image-quality phantom was 4.62%. Spillover ratios in the images of air and water filled chambers were 0.19 and 0.06, respectively. Our results were comparable with the 19 other preclinical PET scanners based on NEMA NU4 standards, with excellent sensitivity because of the large FOV. The ClairvivoPET with iterative reconstruction algorithm also provided sufficient visualization of the mouse spine.The high sensitivity and resolution of the ClairvivoPET scanner provided high quality images for preclinical studies.

Comparison of reconstruction methods and quantitative accuracy in Siemens Inveon PET scanner

PET reconstruction is key to the quantification of PET data. To our knowledge, no comparative study of reconstruction methods has been performed to date. In this study, we compared reconstruction methods with various filters in terms of their spatial resolution, non-uniformities (NU), recovery coefficients (RCs), and spillover ratios (SORs). In addition, the linearity of reconstructed radioactivity between linearity of measured and true concentrations were also assessed.A Siemens Inveon PET scanner was used in this study. Spatial resolution was measured with NEMA standard by using a 1 mm3 sized 18F point source. Image quality was assessed in terms of NU, RC and SOR. To measure the effect of reconstruction algorithms and filters, data was reconstructed using FBP, 3D reprojection algorithm (3DRP), ordered subset expectation maximization 2D (OSEM 2D), and maximum a posteriori (MAP) with various filters or smoothing factors (β). To assess the linearity of reconstructed radioactivity, image quality phantom filled with 18F was used using FBP, OSEM and MAP (β =1.5 & 5 × 10−5).The highest achievable volumetric resolution was 2.31 mm3 and the highest RCs were obtained when OSEM 2D was used. SOR was 4.87% for air and 3.97% for water, obtained OSEM 2D reconstruction was used. The measured radioactivity of reconstruction image was proportional to the injected one for radioactivity below 16 MBq/ml when FBP or OSEM 2D reconstruction methods were used. By contrast, when the MAP reconstruction method was used, activity of reconstruction image increased proportionally, regardless of the amount of injected radioactivity. When OSEM 2D or FBP were used, the measured radioactivity concentration was reduced by 53% compared with true injected radioactivity for radioactivity <16 MBq/ml.The OSEM 2D reconstruction method provides the highest achievable volumetric resolution and highest RC among all the tested methods and yields a linear relation between the measured and true concentrations for radioactivity Our data collectively showed that OSEM 2D reconstruction method provides quantitatively accurate reconstructed PET data results.

Determination of single gamma photon fraction of 124I PET

124I has a half-life of 4.2 days, which makes it suitable for imaging over several days along uptake and washout phases. However, it has a low positron branching ratio (23%), because high-energy gamma photons (602 to 1,691 keV), which degrade image quality, are emitted in cascade with positrons. In this study, we measured the single gamma photon fraction of 124I on Inveon PET scanner. Methods: to measure the single gamma photon fraction (SGF) of 124I, we measured the sensitivities of 124I and 18F from energy windows. The spill over ratios (SORs) of 124I were measured to assess the effect of single gamma photons fractions. Results: the SGF were 31%, 24%, and 3% in 0350 ∼ 75, 0350 ∼ 65, and 0350∼ 55 keV, respectively. After single gamma corrections the SOR was decreased by 13% point. Conclusion: the proposed method for measuring the single gamma photons fraction of 124I will be useful to correct the single gamma photons from 124I PET. This information would also be useful to quantify the 124I PET.

Digital simulation of chronoamperometry at an electrode within a hemispherical polymer drop containing an enzyme: Comparison of a hemispherical with a flat disk electrode

Current-time and steady state current behaviour was simulated for the cases of a hemispherical and flat inlaid disk electrodes located under a hemispherical polymer drop containing an enzyme which converts a substrate diffusing into the drop into a product that is electroactive at the electrode. As well, a cylindrical electrode with length much greater than its diameter and coated with a layer of polymer/enzyme was treated. The ratio of steady state currents at the hemispherical to the disk electrode is not, as has sometimes been assumed, always equal to π/2; indeed this is only approached for polymer drops with large spillover ratio, that is, having a radius much larger than that of the electrodes. Steady state currents for all electrode geometries (including the cylinder) go through a maximum for some spillover ratio and then approach a constant value for larger spillover ratios. This constant value is the same as that for the diffusion limited current in a semi-infinite medium. For a cylindrical electrode, the steady state current tends towards zero for large spillover ratios.

Contrast-enhanced small-animal PET/CT in cancer research: strong improvement of diagnostic accuracy without significant alteration of quantitative accuracy and NEMA NU 4–2008 image quality parameters

BackgroundThe use of iodinated contrast media in small-animal positron emission tomography (PET)/computed tomography (CT) could improve anatomic referencing and tumor delineation but may introduce inaccuracies in the attenuation correction of the PET images. This study evaluated the diagnostic performance and accuracy of quantitative values in contrast-enhanced small-animal PET/CT (CEPET/CT) as compared to unenhanced small animal PET/CT (UEPET/CT).MethodsFirstly, a NEMA NU 4–2008 phantom (filled with 18F-FDG or 18F-FDG plus contrast media) and a homemade phantom, mimicking an abdominal tumor surrounded by water or contrast media, were used to evaluate the impact of iodinated contrast media on the image quality parameters and accuracy of quantitative values for a pertinent-sized target. Secondly, two studies in 22 abdominal tumor-bearing mice and rats were performed. The first animal experiment studied the impact of a dual-contrast media protocol, comprising the intravenous injection of a long-lasting contrast agent mixed with 18F-FDG and the intraperitoneal injection of contrast media, on tumor delineation and the accuracy of quantitative values. The second animal experiment compared the diagnostic performance and quantitative values of CEPET/CT versus UEPET/CT by sacrificing the animals after the tracer uptake period and imaging them before and after intraperitoneal injection of contrast media.ResultsThere was minimal impact on IQ parameters (%SDunif and spillover ratios in air and water) when the NEMA NU 4–2008 phantom was filled with 18F-FDG plus contrast media. In the homemade phantom, measured activity was similar to true activity (−0.02%) and overestimated by 10.30% when vials were surrounded by water or by an iodine solution, respectively. The first animal experiment showed excellent tumor delineation and a good correlation between small-animal (SA)-PET and ex vivo quantification (r2 = 0.87, P < 0.0001). The second animal experiment showed a good correlation between CEPET/CT and UEPET/CT quantitative values (r2 = 0.99, P < 0.0001). Receiver operating characteristic analysis demonstrated better diagnostic accuracy of CEPET/CT versus UEPET/CT (senior researcher, area under the curve (AUC) 0.96 versus 0.77, P = 0.004; junior researcher, AUC 0.78 versus 0.58, P = 0.004).ConclusionsThe use of iodinated contrast media for small-animal PET imaging significantly improves tumor delineation and diagnostic performance, without significant alteration of SA-PET quantitative accuracy and NEMA NU 4–2008 IQ parameters.

Performance Measurements of the MicroPET FOCUS 120 for Iodine-124 Imaging

This study aimed to evaluate the performance of the microPET FOCUS 120 for 124I in terms of counting rate capability and image quality using the NEMA NU 4-2008 methodology. Scanner sensitivity was measured for 124I for comparison and reached 75 cps/kBq, respectively, with the usual 350-650 keV energy window (EW) and 6 ns time window (TW). The noise equivalent count rate (NECR) index was defined as: NECR = RT2 /(RP +RGP) ( T = true, P = prompt, GP = γ-prompt). A rat phantom maximum NECR of 48 kcps was obtained for the 250-590 keV EW with 6 ns TW. An almost identical maximum NECR of 43 kcps was recorded for 350-590 and 350-650 keV EW and 6 ns TW. The 2 ns TW reduced the sensitivity and NECR by 40-50% for all EW. The mouse phantom NECR study was limited because of the maximum available activity concentration of 124I. The 250-590 keV EW showed the largest scatter and γ-prompt plus scatter fractions with 25.7% and 43%, respectively, for the rat phantom and 12.2% and 27% for the mouse phantom. With the 350-590 keV EW, these fractions decreased to 20% and 33.5% for the rat phantom and to 10% and 21% for the mouse phantom. The image quality was investigated with the NEMA NU 4-2008 dedicated phantom for four (two analytic and two iterative) 2D or 3D reconstruction methods. The lowest spillover ratios (SOR) for the phantom non-emitting regions were obtained for the 350-590 and 350-650 keV EWs. Recovery coefficients (RC) of the hot rods were the highest for the 350-590 keV EW except for the 1 mm rod. Scatter correction led to a large decrease in RC. The combination of the 350-590 keV EW with 6 ns TW appeared to be a good compromise between counting rate capability and image quality for the FOCUS 120, especially when maximum a posteriori reconstruction was used without scatter correction. Moreover this combination enabled the best quantification with an error as low as 0.36%.

Using the NEMA NU 4 PET Image Quality Phantom in Multipinhole Small-Animal SPECT

Several commercial small-animal SPECT scanners using multipinhole collimation are presently available. However, generally accepted standards to characterize the performance of these scanners do not exist. Whereas for small-animal PET, the National Electrical Manufacturers Association (NEMA) NU 4 standards have been defined in 2008, such standards are still lacking for small-animal SPECT. In this study, the image quality parameters associated with the NEMA NU 4 image quality phantom were determined for a small-animal multipinhole SPECT scanner. Multiple whole-body scans of the NEMA NU 4 image quality phantom of 1-h duration were performed in a U-SPECT-II scanner using (99m)Tc with activities ranging between 8.4 and 78.2 MBq. The collimator contained 75 pinholes of 1.0-mm diameter and had a bore diameter of 98 mm. Image quality parameters were determined as a function of average phantom activity, number of iterations, postreconstruction spatial filter, and scatter correction. In addition, a mouse was injected with (99m)Tc-hydroxymethylene diphosphonate and was euthanized 6.5 h after injection. Multiple whole-body scans of this mouse of 1-h duration were acquired for activities ranging between 3.29 and 52.7 MBq. An increase in the number of iterations was accompanied by an increase in the recovery coefficients for the small rods (RC(rod)), an increase in the noise in the uniform phantom region, and a decrease in spillover ratios for the cold-air- and water-filled scatter compartments (SOR(air) and SOR(wat)). Application of spatial filtering reduced image noise but lowered RC(rod). Filtering did not influence SOR(air) and SOR(wat). Scatter correction reduced SOR(air) and SOR(wat). The effect of total phantom activity was primarily seen in a reduction of image noise with increasing activity. RC(rod), SOR(air), and SOR(wat) were more or less constant as a function of phantom activity. The relation between acquisition and reconstruction settings and image quality was confirmed in the (99m)Tc-hydroxymethylene diphosphonate mouse scans. Although developed for small-animal PET, the NEMA NU 4 image quality phantom was found to be useful for small-animal SPECT as well, allowing for objective determination of image quality parameters and showing the trade-offs between several of these parameters on variation of acquisition and reconstruction settings.

Characterization and optimization of image quality as a function of reconstruction algorithms and parameter settings in a Siemens Inveon small-animal PET scanner using the NEMA NU 4-2008 standards

The image reconstruction algorithms provided with the Siemens Inveon small-animal PET scanner are filtered backprojection (FBP), 3-dimensional reprojection (3DRP), ordered subset expectation maximization in 2 or 3 dimensions (OSEM2D/3D) and maximum a posteriori (MAP) reconstruction. This study aimed at optimizing the reconstruction parameter settings with regard to image quality (IQ) as defined by the NEMA NU 4-2008 standards. The NEMA NU 4-2008 image quality phantom was used to determine image noise, expressed as percentage standard deviation in the uniform phantom region (%STD unif), activity recovery coefficients for the FDG-filled rods (RC rod), and spill-over ratios for the non-radioactive water- and air-filled phantom compartments (SOR wat and SOR air). Although not required by NEMA NU 4, we also determined a contrast-to-noise ratio for each rod (CNR rod), expressing the trade-off between activity recovery and image noise. For FBP and 3DRP the cut-off frequency of the applied filters, and for OSEM2D and OSEM3D, the number of iterations was varied. For MAP, the “smoothing parameter” β and the type of uniformity constraint (variance or resolution) were varied. Results of these analyses were demonstrated in images of an FDG-injected rat showing tumours in the liver, and of a mouse injected with an 18F-labeled peptide, showing a small subcutaneous tumour and the cortex structure of the kidneys. Optimum IQ in terms of CNR rod for the small-diameter rods was obtained using MAP with uniform variance and β=0.4. This setting led to RC rod,1 mm=0.21, RC rod,2 mm=0.57, %STD unif=1.38, SOR wat=0.0011, and SOR air=0.00086. However, the highest activity recovery for the smallest rods with still very small %STD unif was obtained using β=0.075, for which these IQ parameters were 0.31, 0.74, 2.67, 0.0041, and 0.0030, respectively. The different settings of reconstruction parameters were clearly reflected in the rat and mouse images as the trade-off between the recovery of small structures (blood vessels, small tumours, kidney cortex structure) and image noise in homogeneous body parts (healthy liver background). Highest IQ for the Inveon PET scanner was obtained using MAP reconstruction with uniform variance. The setting of β depended on the specific imaging goals.

High-throughput small animal PET imaging in cancer research: evaluation of the capability of the Inveon scanner to image four mice simultaneously

The aim of this study was to assess the capability of small animal PET (SA-PET) devices to image four mice simultaneously to improve the throughput of SA-PET experiments in cancer research. A customized bed was designed to image up to four mice simultaneously. This bed can easily replace the bed provided by the manufacturer and is connected to an anaesthesia device. A mouse-sized phantom was imaged, mimicking simultaneous imaging of four mice with computation of recovery coefficients and spillover ratios (SORs). In addition, eight mice bearing subcutaneous tumours (human embryonal carcinoma, n=22 tumours) were simultaneously imaged in groups of four on an Inveon SA-PET scanner after injection of F-fluoro-D-glucose. Tumour activity (Bq/ml), as determined by the SA-PET, was compared with ex-vivo counting. For a 5-mm rod, recovery coefficients were 1.15 and 1.05 for a phantom imaged at the central field of view or off-centred on the customized bed, respectively. SORair and SORwater were 0.05 and 0.04 for a phantom imaged alone and 0.15 and 0.06 for a phantom imaged with three additional scatter sources, respectively. Correlation between SA-PET and ex-vivo quantification was good (r=0.91, P<0.0001). The mean ratio of PET quantitative data and ex-vivo counting was equal to 0.9 (95% confidence interval: 0.70-1.09). New generation SA-PET may be suitable for simultaneously imaging four tumour-bearing mice, although improvement in scatter correction efficiency appears necessary. The type of customized bed developed in this study could be easily adapted to other large-bore SA-PET scanners.

Scanning multiple mice in a small-animal PET scanner: Influence on image quality

To achieve high throughput in small-animal positron emission tomography (PET), it may be advantageous to scan more than one animal in the scanner’s field of view (FOV) at the same time.However, due to the additional activity and increase of Poisson noise, additional attenuating mass, extra photon scattering, and radial or axial displacement of the animals, a deterioration of image quality can be expected. In this study, the NEMA NU 4-2008 image quality (NU4IQ) phantom and up to three FDG-filled cylindrical “mouse phantoms” were positioned in the FOV of the Siemens Inveon small-animal PET scanner to simulate scans with multiple mice. Five geometrical configurations were examined. In one configuration, the NU4IQ phantom was scanned separately and placed in the center of the FOV (1C). In two configurations, a mouse phantom was added with both phantoms displaced radially (2R) or axially (2A). In two other configurations, the NU4IQ phantom was scanned along with three mouse phantoms with all phantoms displaced radially (4R), or in a combination of radial and axial displacement (2R2A). Images were reconstructed using ordered subset expectation maximization in 2 dimensions (OSEM2D) and maximum a posteriori (MAP) reconstruction. Image quality parameters were obtained according to the NEMA NU 4-2008 guidelines. Optimum image quality was obtained for the 1C geometry. Image noise increased by the addition of phantoms and was the largest for the 4R configuration. Spatial resolution, reflected in the recovery coefficients for the FDG-filled rods, deteriorated by radial displacement of the NU4IQ phantom (2R, 2R2A, and 4R), most strongly for OSEM2D, and to a smaller extent for MAP reconstructions. Photon scatter, as indicated by the spill-over ratios in the non-radioactive water- and air-filled compartments, increased by the addition of phantoms, most strongly for the 4R configuration. Application of scatter correction substantially lowered the spill-over ratios, but caused an over-correction for the recovery coefficients of the FDG-filled rods when the phantom was displaced radially. Image noise was not substantially influenced by scatter correction. In conclusion, when scanning 2 mice, axial displacement (2A) is preferable above to radial displacement (2R) since for axial displacement, the recovery coefficients are higher and spill-over ratios are lower, whereas image noise remains similar. In the case of scanning 4 mice, combined axial and radial displacement (2R2A) is preferable to just radial displacement (4R).

Image-Quality Assessment for Several Positron Emitters Using the NEMA NU 4-2008 Standards in the Siemens Inveon Small-Animal PET Scanner

The positron emitters (18)F, (68)Ga, (124)I, and (89)Zr are all relevant in small-animal PET. Each of these radionuclides has different positron energies and ranges and a different fraction of single photons emitted. Average positron ranges larger than the intrinsic spatial resolution of the scanner (for (124)I and (68)Ga) will deteriorate the effective spatial resolution and activity recovery coefficient (RC) for small lesions or phantom structures. The presence of single photons (for (124)I and (89)Zr) could increase image noise and spillover ratios (SORs). Image noise, expressed as percentage SD in a uniform region (%SD), RC, and SOR (in air and water) were determined using the NEMA NU 4 small-animal image-quality phantom filled with 3.7 MBq of total activity of (18)F, (68)Ga, (124)I, or (89)Zr. Filtered backprojection (FBP), ordered-subset expectation maximization in 2 dimensions, and maximum a posteriori (MAP) reconstructions were compared. In addition to the NEMA NU 4 image-quality parameters, spatial resolutions were determined using small glass capillaries filled with these radionuclides in a water environment. The %SD for (18)F, (68)Ga, (124)I, and (89)Zr using FBP was 6.27, 6.40, 6.74, and 5.83, respectively. The respective RCs were 0.21, 0.11, 0.12, and 0.19 for the 1-mm-diameter rod and 0.97, 0.65, 0.64, and 0.88 for the 5-mm-diameter rod. SORs in air were 0.01, 0.03, 0.04, and 0.01, respectively, and in water 0.02, 0.10, 0.13, and 0.02. Other reconstruction algorithms gave similar differences between the radionuclides. MAP produced the highest RCs. For the glass capillaries using FBP, the full widths at half maximum for (18)F, (68)Ga, (124)I, and (89)Zr were 1.81, 2.46, 2.38, and 1.99 mm, respectively. The corresponding full widths at tenth maximum were 3.57, 6.52, 5.87, and 4.01 mm. With the intrinsic spatial resolution (approximately 1.5 mm) of this latest-generation small-animal PET scanner, the finite positron range has become the limiting factor for the overall spatial resolution and activity recovery in small structures imaged with (124)I and (68)Ga. The presence of single photons had only a limited effect on the image noise. MAP, as compared with the other reconstruction algorithms, increased RC and decreased %SD and SOR.

High throughput static and dynamic small animal imaging using clinical PET/CT: potential preclinical applications

The objective of the study was to evaluate state-of-the-art clinical PET/CT technology in performing static and dynamic imaging of several mice simultaneously. A mouse-sized phantom was imaged mimicking simultaneous imaging of three mice with computation of recovery coefficients (RCs) and spillover ratios (SORs). Fifteen mice harbouring abdominal or subcutaneous tumours were imaged on clinical PET/CT with point spread function (PSF) reconstruction after injection of [18F]fluorodeoxyglucose or [18F]fluorothymidine. Three of these mice were imaged alone and simultaneously at radial positions -5, 0 and 5 cm. The remaining 12 tumour-bearing mice were imaged in groups of 3 to establish the quantitative accuracy of PET data using ex vivo gamma counting as the reference. Finally, a dynamic scan was performed in three mice simultaneously after the injection of (68)Ga-ethylenediaminetetraacetic acid (EDTA). For typical lesion sizes of 7-8 mm phantom experiments indicated RCs of 0.42 and 0.76 for ordered subsets expectation maximization (OSEM) and PSF reconstruction, respectively. For PSF reconstruction, SOR(air) and SOR(water) were 5.3 and 7.5%, respectively. A strong correlation (r (2) = 0.97, p < 0.0001) between quantitative data obtained in mice imaged alone and simultaneously in a group of three was found following PSF reconstruction. The correlation between ex vivo counting and PET/CT data was better with PSF reconstruction (r (2) = 0.98; slope = 0.89, p < 0.0001) than without (r (2) = 0.96; slope = 0.62, p < 0.001). Valid time-activity curves of the blood pool, kidneys and bladder could be derived from (68)Ga-EDTA dynamic acquisition. New generation clinical PET/CT can be used for simultaneous imaging of multiple small animals in experiments requiring high throughput and where a dedicated small animal PET system is not available.

Efficiency and equity considerations in financing agricultural research and extension

Benefits resulting from agricultural research and extension activities conducted in one region may affect producers and consumers throughout the country. Measurement of these benefit spillovers is required to equitably and efficiently finance these activities. Spillover benefit ratios per dollar of internal benefits for all farm production regions in the United States are calculated using an economic surplus framework to account for the effects of research and extension on both producers and consumers. In nine out of ten regions, the spillover ratios are greater than one, indicating that benefits accruing outside the region conducting research and extension activities are greater than the benefits accruing internally to the region. The average spillover ratio, which is 3.71 for all regions, is greater than the ratio of federal expenditures to regional expenditures. The implication of these ratios being unequal is that the federal contribution would need to be increased in order for regional costs to match regional benefits.