A Monte Carlo and physical phantom evaluation of quantitative In-111 SPECT

Accurate estimation of the 3D in vivo activity distribution is important for dose estimation in targeted radionuclide therapy (TRT). Although SPECT can potentially provide such estimates, SPECT without compensation for image degrading factors is not quantitatively accurate. In this work, we evaluated quantitative SPECT (QSPECT) reconstruction methods that include compensation for various physical effects. Experimental projection data were obtained using a GE VH/Hawkeye system and an RSD torso phantom. Known activities of In-111 chloride were placed in the lungs, liver, heart, background and two spherical compartments with inner diameters of 22 mm and 34 mm. The 3D NCAT phantom with organ activities based on clinically derived In-111 ibritumomab tiuxetan data was used for the Monte Carlo (MC) simulation studies. Low-noise projection data were simulated using previously validated MC simulation methods. Fifty sets of noisy projections with realistic count levels were generated. Reconstructions were performed using the OS-EM algorithm with various combinations of attenuation (A), scatter (S), geometric response (G), collimator-detector response (D) and partial volume compensation (PVC). The QSPECT images from the various combinations of compensations were evaluated in terms of the accuracy and precision of the estimates of the total activity in each organ. For experimental data, the errors in organ activities for ADS and PVC compensation were less than 6.5% except the smaller sphere (-11.9%). For the noisy simulated data, the errors in organ activity for ADS compensation were less than 5.5% except the lungs (20.9%) and blood vessels (15.2%). Errors for other combinations of compensations were significantly (A, AS) or somewhat (AGS) larger. With added PVC, the error in the organ activities improved slightly except for the lungs (11.5%) and blood vessels (3.6%) where the improvement was more substantial. The standard deviation/mean ratios were all less than 1.5%. We conclude that QSPECT methods with appropriate compensations provided accurate In-111 organ activity estimates. For the collimator used, AGS was almost as good as ADS and may be preferable due to the reduced reconstruction time. PVC was important for small structures such as tumours or for organs in close proximity to regions with high activity. The improved quantitative accuracy from QSPECT methods has the potential for improving organ dose estimations in TRT.     

Integration of SimSET photon history generator in GATE for efficient Monte Carlo simulations of pinhole SPECT

The authors developed and validated an efficient Monte Carlo simulation (MCS) workflow to facilitate small animal pinhole SPECT imaging research. This workflow seamlessly integrates two existing MCS tools: simulation system for emission tomography (SimSET) and GEANT4 application for emission tomography (GATE). Specifically, we retained the strength of GATE in describing complex collimator/detector configurations to meet the anticipated needs for studying advanced pinhole collimation (e.g., multipinhole) geometry, while inserting the fast SimSET photon history generator (PHG) to circumvent the relatively slow GEANT4 MCS code used by GATE in simulating photon interactions inside voxelized phantoms. For validation, data generated from this new SimSET-GATE workflow were compared with those from GATE-only simulations as well as experimental measurements obtained using a commercial small animal pinhole SPECT system. Our results showed excellent agreement (e.g., in system point response functions and energy spectra) between SimSET-GATE and GATE-only simulations, and, more importantly, a significant computational speedup (up to approximately 10-fold) provided by the new workflow. Satisfactory agreement between MCS results and experimental data were also observed. In conclusion, the authors have successfully integrated SimSET photon history generator in GATE for fast and realistic pinhole SPECT simulations, which can facilitate research in, for example, the development and application of quantitative pinhole and multipinhole SPECT for small animal imaging. This integrated simulation tool can also be adapted for studying other preclinical and clinical SPECT techniques.     

Contrasting properties of gold nanoparticles for optical coherence tomography: phantom, in vivo studies and Monte Carlo simulation

The possibility of using silica-gold nanoshells with 150 nm silica core size and 25 nm thick gold shell as contrasting agents for optical coherence tomography (OCT) is analyzed. Experiments on agar biotissue phantoms showed that the penetration of nanoshells into the phantoms increases the intensity of the optical coherence tomography (OCT) signal and the brightness of the corresponding areas of the OCT image. In vivo experiments on rabbit skin demonstrated that the application of nanoshells onto the skin provides significant contrasting of the borders between the areas containing nanoshells and those without. This effect of nanoshells on skin in vivo is manifested by the increase in intensity of the OCT signal in superficial parts of the skin, boundary contrast between superficial and deep dermis and contrast of hair follicles and glands. The presence of nanoshells in the skin was confirmed by electron microscopy. Monte Carlo simulations of OCT images confirmed the possibility of contrasting skin-layer borders and structures by the application of gold nanoshells. The Monte Carlo simulations were performed for two skin models and exhibit effects of nanoparticles similar to those obtained in the experimental part of the study, thus proving that the effects originate exactly from the presence of nanoparticles.     

Radiation dose in diagnostic radiology: Monte Carlo simulation studies

We applied Monte Carlo calculations to determine the radiation dose absorbed in water phantoms. Monoenergetic incident x-ray beams with energies from 15 to 100 keV and phantom thicknesses from 5 to 20 cm were considered in this study. We calculated the spatial distributions of energy absorption in the phantom, the rad/R conversion factors, the average rad/R conversion factors, and the scatter-to-primary ratios of absorbed dose. We also compared the relative absorbed doses under various imaging conditions when the transmitted radiation produced a given optical density on radiographic film. The information provided will be useful for the estimation of radiation doses in various radiographic procedures.     

Evaluation of criteria for classical dissociations in single-case studies by Monte Carlo simulation

The conventional criteria for a classical dissociation in single-case studies require that a patient be impaired on one task and within normal limits on another. J. R. Crawford and P. H. Garthwaite (2005) proposed an additional criterion, namely, that the patient's (standardized) difference on the two tasks should differ from the distribution of differences in controls. Monte Carlo simulation was used to evaluate these criteria. When Type I errors were defined as falsely concluding that a control case exhibited a dissociation, error rates were high for the conventional criteria but low for Crawford and Garthwaite's criteria. When Type I error rates were defined as falsely concluding that a patient with equivalent deficits on the two tasks exhibited a dissociation, error rates were very high for the conventional criteria but acceptable for the latter criteria. These latter criteria were robust in the face of nonnormal control data. The power to detect classical dissociations was studied.     

Monte Carlo studies of x-ray scattering in transmission diagnostic radiology

Monte Carlo methods have been used to simulate the scattering of x rays in polystyrene and water phantoms. In particular, the ratio of the scattered to total x-ray fluence (scatter fraction) has been calculated for monoenergetic x-ray beams in the energy region relevant to diagnostic radiology and nuclear medicine (30-660 keV). Simulations have been made for representative values of the pertinent geometrical factors; phantom thickness from 5 to 21 cm, x-ray beam diameters of 10 and 25 cm, and scatterer-to-image-plane separations from 0 to 20 cm. As a function of x-ray energy, the scatter fraction was found to vary slowly between 30 and 100 keV, and to decrease between 100 and 660 keV. The present results were generated with a special transport code which included the effects of special geometries and the response of the x-ray detector. With the inclusion of these effects, the results resolved inconsistencies and showed good agreement with previous measured and calculated data.     

Fast modelling of the collimator-detector response in Monte Carlo simulation of SPECT imaging using the angular response function

Interactions of incident photons with the collimator and detector, including septal penetration, scatter and x-ray fluorescence, are significant sources of image degradation in applications of SPECT including dual isotope imaging and imaging using radioisotopes that emit high- or medium-energy photons. Modelling these interactions using full Monte Carlo (MC) simulations is computationally very demanding. We present a new method based on the use of angular response functions (ARFs). The ARF is a function of the incident photon's direction and energy and represents the probability that a photon will either interact with or pass through the collimator, and be detected at the intersection of the photon's direction vector and the detection plane in an energy window of interest. The ARFs were pre-computed using full MC simulations of point sources that include propagation through the collimator-detector system. We have implemented the ARF method for use in conjunction with the SimSET/PHG MC code to provide fast modelling of both interactions in the patient and in the collimator-detector system. Validation results in the three cases studied show that there was good agreement between the projections generated using the ARF method and those from previously validated full MC simulations, but with hundred to thousand fold reductions in simulation time.     

Methods of testing for a deficit in single-case studies: Evaluation of statistical power by Monte Carlo simulation

Testing for the presence of a deficit by comparing a case to controls is a fundamental feature of many neuropsychological single-case studies. Monte Carlo simulation was employed to study the statistical power of two competing approaches to this task. The power to detect a large deficit was low to moderate for a method proposed by Crawford and Howell (1998; ranging from 44% to 63%) but was extremely low for a method proposed by Mycroft, Mitchell, and Kay (2002; ranging from 1% to 13%). The effects of departures from normality were examined, as was the effect of varying degrees of measurement error in the scores of controls and the single case. Measurement error produced a moderate reduction in power when present in both controls and the case; the effect of differentially greater measurement error for the single case depended on the initial level of power. When Mycroft et al.'s method was used to test for the presence of a classical dissociation, it produced very high Type I error rates (ranging from 20.7% to 49.3%); in contrast, the rates for criteria proposed by Crawford and Garthwaite (2005b) were low (ranging from 1.3% to 6.7%). The broader implications of these results for single-case research are discussed.     

Methods of testing for a deficit in single-case studies: Evaluation of statistical power by Monte Carlo simulation

Testing for the presence of a deficit by comparing a case to controls is a fundamental feature of many neuropsychological single-case studies. Monte Carlo simulation was employed to study the statistical power of two competing approaches to this task. The power to detect a large deficit was low to moderate for a method proposed by Crawford and Howell (1998; ranging from 44% to 63%) but was extremely low for a method proposed by Mycroft, Mitchell, and Kay (2002; ranging from 1% to 13%). The effects of departures from normality were examined, as was the effect of varying degrees of measurement error in the scores of controls and the single case. Measurement error produced a moderate reduction in power when present in both controls and the case; the effect of differentially greater measurement error for the single case depended on the initial level of power. When Mycroft et al.'s method was used to test for the presence of a classical dissociation, it produced very high Type I error rates (ranging from 20.7% to 49.3%); in contrast, the rates for criteria proposed by Crawford and Garthwaite (2005b) were low (ranging from 1.3% to 6.7%). The broader implications of these results for single-case research are discussed.     

Correction for scatter and septal penetration using convolution subtraction methods and model-based compensation in 123I brain SPECT imaging-a Monte Carlo study

Scatter and septal penetration deteriorate contrast and quantitative accuracy in single photon emission computed tomography (SPECT). In this study four different correction techniques for scatter and septal penetration are evaluated for 123I brain SPECT. One of the methods is a form of model-based compensation which uses the effective source scatter estimation (ESSE) for modelling scatter, and collimator-detector response (CDR) including both geometric and penetration components. The other methods, which operate on the 2D projection images, are convolution scatter subtraction (CSS) and two versions of transmission dependent convolution subtraction (TDCS), one of them proposed by us. This method uses CSS for correction for septal penetration, with a separate kernel, and TDCS for scatter correction. The corrections are evaluated for a dopamine transporter (DAT) study and a study of the regional cerebral blood flow (rCBF), performed with 123I. The images are produced using a recently developed Monte Carlo collimator routine added to the program SIMIND which can include interactions in the collimator. The results show that the method included in the iterative reconstruction is preferable to the other methods and that the new TDCS version gives better results compared with the other 2D methods.     

Physical characteristics of scattered radiation in diagnostic radiology: Monte Carlo simulation studies

We applied Monte Carlo methods for the simulation of x-ray scattering in water phantoms. The phantom thickness was varied from 5 to 20 cm, and the monoenergetic incident x rays were varied from 15 to 100 keV. Eight screen pairs and a total absorption system were used as x-ray receptors. We determined the angular, spectral, and spatial distributions of the scattered radiation and the scatter fractions recorded in the image plane. The dependence of these properties on the incident x-ray energy, the phantom thickness, and the energy response of the recording system was examined. The results of this study provide useful information for the development of antiscatter techniques and for the evaluation of radiographic procedures.     

Study of the point spread function (PSF) for 123I SPECT imaging using Monte Carlo simulation

The iterative reconstruction algorithms employed in brain single-photon emission computed tomography (SPECT) allow some quantitative parameters of the image to be improved. These algorithms require accurate modelling of the so-called point spread function (PSF). Nowadays, most in vivo neurotransmitter SPECT studies employ pharmaceuticals radiolabelled with 123I. In addition to an intense line at 159 keV, the decay scheme of this radioisotope includes some higher energy gammas which may have a non-negligible contribution to the PSF. The aim of this work is to study this contribution for two low-energy high-resolution collimator configurations, namely, the parallel and the fan beam. The transport of radiation through the material system is simulated with the Monte Carlo code PENELOPE. We have developed a main program that deals with the intricacies associated with tracking photon trajectories through the geometry of the collimator and detection systems. The simulated PSFs are partly validated with a set of experimental measurements that use the 511 keV annihilation photons emitted by a 18F source. Sensitivity and spatial resolution have been studied, showing that a significant fraction of the detection events in the energy window centred at 159 keV (up to approximately 49% for the parallel collimator) are originated by higher energy gamma rays, which contribute to the spatial profile of the PSF mostly outside the 'geometrical' region dominated by the low-energy photons. Therefore, these high-energy counts are to be considered as noise, a fact that should be taken into account when modelling PSFs for reconstruction algorithms. We also show that the fan beam collimator gives higher signal-to-noise ratios than the parallel collimator for all the source positions analysed.     

Performance of antiscatter grids in diagnostic radiology: experimental measurements and Monte Carlo simulation studies

We have devised an experimental method with which one can accurately measure the transmission of primary radiation and the transmission of total radiation by an antiscatter grid in a setting similar to a practical radiographic examination. We measured the transmission values for 27 combinations of x-ray tube potentials, phantom thicknesses, screen-film systems, and grid parameters. The standard deviation of one measurement was estimated to be 2.9% and 1.5% for the total and primary transmissions, respectively. The measured grid transmission was compared with results predicted by our Monte Carlo calculations; 92% of the measured and calculated values agree within two standard deviations. This close agreement indicates that our Monte Carlo calculation can accurately predict the performance of antiscatter grids under diagnostic imaging conditions.     

Investigation of dynamic SPECT measurements of the arterial input function in human subjects using simulation, phantom and human studies

Computer simulations, a phantom study and a human study were performed to determine whether a slowly rotating single-photon computed emission tomography (SPECT) system could provide accurate arterial input functions for quantification of myocardial perfusion imaging using kinetic models. The errors induced by data inconsistency associated with imaging with slow camera rotation during tracer injection were evaluated with an approach called SPECT/P (dynamic SPECT from positron emission tomography (PET)) and SPECT/D (dynamic SPECT from database of SPECT phantom projections). SPECT/P simulated SPECT-like dynamic projections using reprojections of reconstructed dynamic (94)Tc-methoxyisobutylisonitrile ((94)Tc-MIBI) PET images acquired in three human subjects (1 min infusion). This approach was used to evaluate the accuracy of estimating myocardial wash-in rate parameters K(1) for rotation speeds providing 180° of projection data every 27 or 54 s. Blood input and myocardium tissue time-activity curves (TACs) were estimated using spatiotemporal splines. These were fit to a one-compartment perfusion model to obtain wash-in rate parameters K(1). For the second method (SPECT/D), an anthropomorphic cardiac torso phantom was used to create real SPECT dynamic projection data of a tracer distribution derived from (94)Tc-MIBI PET scans in the blood pool, myocardium, liver and background. This method introduced attenuation, collimation and scatter into the modeling of dynamic SPECT projections. Both approaches were used to evaluate the accuracy of estimating myocardial wash-in parameters for rotation speeds providing 180° of projection data every 27 and 54 s. Dynamic cardiac SPECT was also performed in a human subject at rest using a hybrid SPECT/CT scanner. Dynamic measurements of (99m)Tc-tetrofosmin in the myocardium were obtained using an infusion time of 2 min. Blood input, myocardium tissue and liver TACs were estimated using the same spatiotemporal splines. The spatiotemporal maximum-likelihood expectation-maximization (4D ML-EM) reconstructions gave more accurate reconstructions than did standard frame-by-frame static 3D ML-EM reconstructions. The SPECT/P results showed that 4D ML-EM reconstruction gave higher and more accurate estimates of K(1) than did 3D ML-EM, yielding anywhere from a 44% underestimation to 24% overestimation for the three patients. The SPECT/D results showed that 4D ML-EM reconstruction gave an overestimation of 28% and 3D ML-EM gave an underestimation of 1% for K(1). For the patient study the 4D ML-EM reconstruction provided continuous images as a function of time of the concentration in both ventricular cavities and myocardium during the 2 min infusion. It is demonstrated that a 2 min infusion with a two-headed SPECT system rotating 180° every 54 s can produce measurements of blood pool and myocardial TACs, though the SPECT simulation studies showed that one must sample at least every 30 s to capture a 1 min infusion input function.     

Photon penetration and scatter in micro-pinhole imaging: a Monte Carlo investigation

Pinhole SPECT is rapidly gaining popularity for imaging laboratory animals using gamma-emitting molecules. Penetration and scattering of gamma radiation in the pinhole edge material can account for a significant fraction of the total number of photons detected, particularly if the pinholes have small diameters. This study characterizes the effects of penetration and scatter with micro-pinholes made of lead, tungsten, gold and platinum. Monte Carlo simulations are performed for 1-125 (27-35 keV) and Tc-99m (140 keV) point sources with pinhole diameters ranging from 50 to 500 microm. The simulations account for the effects of photo-electric interaction, Rayleigh scattering, Compton scattering, ionization, bremsstrahlung and electron multiple scattering. As a typical example, in the case of a Tc-99m point source and pinholes with a diameter of 300 microm in gold or platinum, approximately 55% of the photons detected resulted from penetration and approximately 3% from scatter. For pinhole diameters ranging from 100 to 500 microm, the penetration fraction for tungsten and lead was approx a factor of 1.0 to 1.6 higher and the scatter fraction was 1.0 to 1.8 times higher than in case of gold or platinum. Using I-125 instead of Tc-99m decreases the penetration fraction by a factor ranging from 3 to 11 and the scatter fraction by a factor ranging from 12 to 40. For all materials studied, the total amounts of penetrated and scattered photons changed approximately linearly with respect to the pinhole diameter.     

Evaluation of quantitative (90)Y SPECT based on experimental phantom studies

In SPECT imaging of pure beta emitters, such as (90)Y, the acquired spectrum is very complex, which increases the demands on the imaging protocol and the reconstruction. In this work, we have evaluated the quantitative accuracy of bremsstrahlung SPECT with focus on the reconstruction algorithm including model-based attenuation, scatter and collimator-detector response (CDR) compensations. The scatter and CDR compensation methods require pre-calculated point-spread functions, which were generated with the SIMIND MC program. The SIMIND program is dedicated for simulation of scintillation camera imaging and only handles photons. The aim of this work was therefore twofold. The first aim was to implement simulation of bremsstrahlung imaging into the SIMIND code and to validate simulations against experimental measurements. The second was to investigate the quality of bremsstrahlung SPECT imaging and to evaluate the possibility of quantifying the activity in differently shaped sources. In addition, a feasibility test was performed on a patient that underwent treatment with (90)Y-Ibritumomab tiuxetan (Zevalin). The MCNPX MC program was used to generate bremsstrahlung photon spectra which were used as source input in the SIMIND program. The obtained bremsstrahlung spectra were separately validated by experimental measurement using a HPGe detector. Validation of the SIMIND generated images was done by a comparison to gamma camera measurements of a syringe containing (90)Y. Results showed a slight deviation between simulations and measurements in image regions outside the source, but the agreement was sufficient for the purpose of generating scatter and CDR kernels. For the bremsstrahlung SPECT experiment, the RSD torso phantom with (90)Y in the liver insert was measured with and without background activities. Projection data were obtained using a GE VH/Hawkeye system. Image reconstruction was performed by using the OSEM algorithm with and without different combinations of model-based attenuation, scatter and CDR compensations. The reconstructed images were then evaluated in terms of the accuracy of the total activity estimate in the liver insert. It was found that the activity in a large source such as the liver was estimated with a bias of around -70%, when no compensations were included in the reconstruction, whereas when compensations were included the bias obtained was between -10 and 16%. It is concluded that although the (90)Y bremsstrahlung spectrum is continuous with no pronounced peak and the count rate is low, it is possible to achieve reasonably accurate activity estimates from bremsstrahlung SPECT images if proper compensations are applied in the reconstruction. This conclusion was also confirmed by the patient study.     

Fully 3D Monte Carlo reconstruction in SPECT: a feasibility study

In single photon emission computed tomography (SPECT) with parallel hole collimation, image reconstruction is usually performed as a set of bidimensional (2D) analytical or iterative reconstructions. This approach ignores the tridimensional (3D) nature of scatter and detector response function that affects the detected signal. To deal with the 3D nature of the image formation process, iterative reconstruction can be used by considering a 3D projector modelling the 3D spread of photons. In this paper, we investigate the value of using accurate Monte Carlo simulations to determine the 3D projector used in a fully 3D Monte Carlo (F3DMC) reconstruction approach. Given the 3D projector modelling all physical effects affecting the imaging process, the reconstruction problem is solved using the maximum likelihood expectation maximization (MLEM) algorithm. To validate the concept, three data sets were simulated and F3DMC was compared with two other 3D reconstruction strategies using analytical corrections for attenuation, scatter and camera point spread function. Results suggest that F3DMC improves spatial resolution, relative and absolute quantitation and signal-to-noise ratio. The practical feasibility of the approach on real data sets is discussed.     

A polygon-surface reference Korean male phantom (PSRK-Man) and its direct implementation in Geant4 Monte Carlo simulation

Even though the hybrid phantom embodies both the anatomic reality of voxel phantoms and the deformability of stylized phantoms, it must be voxelized to be used in a Monte Carlo code for dose calculation or some imaging simulation, which incurs the inherent limitations of voxel phantoms. In the present study, a voxel phantom named VKH-Man (Visible Korean Human-Man), was converted to a polygon-surface phantom (PSRK-Man, Polygon-Surface Reference Korean-Man), which was then adjusted to the Reference Korean data. Subsequently, the PSRK-Man polygon phantom was directly, without any voxelization process, implemented in the Geant4 Monte Carlo code for dose calculations. The calculated dose values and computation time were then compared with those of HDRK-Man (High Definition Reference Korean-Man), a corresponding voxel phantom adjusted to the same Reference Korean data from the same VKH-Man voxel phantom. Our results showed that the calculated dose values of the PSRK-Man surface phantom agreed well with those of the HDRK-Man voxel phantom. The calculation speed for the PSRK-Man polygon phantom though was 70-150 times slower than that of the HDRK-Man voxel phantom; that speed, however, could be acceptable in some applications, in that direct use of the surface phantom PSRK-Man in Geant4 does not require a separate voxelization process. Computing speed can be enhanced, in future, either by optimizing the Monte Carlo transport kernel for the polygon surfaces or by using modern computing technologies such as grid computing and general-purpose computing on graphics processing units programming.