Improved activity estimation with MC-JOSEM versus TEW-JOSEM in 111In SPECT

We have previously developed a fast Monte Carlo (MC)-based joint ordered-subset expectation maximization (JOSEM) iterative reconstruction algorithm, MC-JOSEM. A phantom study was performed to compare quantitative imaging performance of MC-JOSEM with that of a triple-energy-window approach (TEW) in which estimated scatter was also included additively within JOSEM, TEW-JOSEM. We acquired high-count projections of a 5.5 cm3 sphere of 111In at different locations in the water-filled torso phantom; high-count projections were then obtained with 111In only in the liver or only in the soft-tissue background compartment, so that we could generate synthetic projections for spheres surrounded by various activity distributions. MC scatter estimates used by MC-JOSEM were computed once after five iterations of TEW-JOSEM. Images of different combinations of liver/background and sphere/background activity concentration ratios were reconstructed by both TEW-JOSEM and MC-JOSEM for 40 iterations. For activity estimation in the sphere, MC-JOSEM always produced better relative bias and relative standard deviation than TEW-JOSEM for each sphere location, iteration number, and activity combination. The average relative bias of activity estimates in the sphere for MC-JOSEM after 40 iterations was -6.9%, versus -15.8% for TEW-JOSEM, while the average relative standard deviation of the sphere activity estimates was 16.1% for MC-JOSEM, versus 27.4% for TEW-JOSEM. Additionally, the average relative bias of activity concentration estimates in the liver and the background for MC-JOSEM after 40 iterations was -3.9%, versus -12.2% for TEW-JOSEM, while the average relative standard deviation of these estimates was 2.5% for MC-JOSEM, versus 3.4% for TEW-JOSEM. MC-JOSEM is a promising approach for quantitative activity estimation in 111In SPECT.     

Evaluation of penetration and scattering components in conventional pinhole SPECT: phantom studies using Monte Carlo simulation

In quantitative pinhole SPECT, photon penetration through the collimator edges (penetration), and photon scattering by the object (object scatter) and collimator (collimator scatter) have not been investigated rigorously. Monte Carlo simulation was used to evaluate these three physical processes for different tungsten knife-edge pinhole collimators using uniform, hotspot and donut phantoms filled with 201Tl, 99mTc, 123I and 131I solutions. For the hotspot phantom, the penetration levels with respect to total counts for a 1 mm pinhole aperture were 78%, 28% and 23% for 131I, 123I and 99mTc, respectively. For a 2 mm aperture, these values were 65% for 131I, 16% for 123I and 12% for 99mTc. For all pinholes, 201Tl penetration was less than 4%. The evaluated scatter (from object and collimator) with a hotspot phantom for the 1 mm pinhole was 24%, 16%, 18% and 13% for 201Tl, 99mTc, 123I and 131I, respectively. Summation of the object and collimator scatter for the uniform phantom was approximately 20% higher than that for the hotspot phantom. Significant counts due to penetration and object and collimator scatter in the reconstructed image were observed inside the core of the donut phantom. The collimator scatter can be neglected for all isotopes used in this study except for 131I. Object scatter correction for all radionuclides used in this study is necessary and correction for the penetration contribution is necessary for all radionuclides but 201Tl.     

Generalized five-dimensional dynamic and spectral factor analysis

We have generalized the spectral factor analysis and the factor analysis of dynamic sequences (FADS) in SPECT imaging to a five-dimensional general factor analysis model (5D-GFA), where the five dimensions are the three spatial dimensions, photon energy, and time. The generalized model yields a significant advantage in terms of the ratio of the number of equations to that of unknowns in the factor analysis problem in dynamic SPECT studies. We solved the 5D model using a least-squares approach. In addition to the traditional non-negativity constraints, we constrained the solution using a priori knowledge of both time and energy, assuming that primary factors (spectra) are Gaussian-shaped with full-width at half-maximum equal to gamma camera energy resolution. 5D-GFA was validated in a simultaneous pre-/post-synaptic dual isotope dynamic phantom study where 99mTc and 123I activities were used to model early Parkinson disease studies. 5D-GFA was also applied to simultaneous perfusion/dopamine transporter (DAT) dynamic SPECT in rhesus monkeys. In the striatal phantom, 5D-GFA yielded significantly more accurate and precise estimates of both primary 99mTc (bias=6.4 % +/- 4.3 %) and 1231 (-1.7% +/- 6.9%) time activity curves (TAC) compared to conventional FADS (biases = 15.5% +/- 10.6% in 99mTc and 8.3% +/- 12.7% in 123I, p < 0.05). Our technique was also validated in two primate dynamic dual isotope perfusion/DAT transporter studies. Biases of 99mTc-HMPAO and 123I-DAT activity estimates with respect to estimates obtained in the presence of only one radionuclide (sequential imaging) were significantly lower with 5D-GFA (9.4% +/- 4.3% for 99mTc-HMPAO and 8.7% +/-4.1% for 123I-DAT) compared to biases greater than 15% for volumes of interest (VOI) over the reconstructed volumes (p < 0.05). 5D-GFA is a novel and promising approach in dynamic SPECT imaging that can also be used in other modalities. It allows accurate and precise dynamic analysis while compensating for Compton scatter and cross-talk.     

Quantification in simultaneous (99m)Tc/(123)I brain SPECT using generalized spectral factor analysis: a Monte Carlo study

In SPECT, simultaneous (99m)Tc/(123)I acquisitions allow comparison of the distribution of two radiotracers in the same physiological state, without any image misregistration, but images can be severely distorted due to cross-talk between the two isotopes. We propose a generalized spectral factor analysis (GSFA) method for solving the cross-talk issue in simultaneous (99m)Tc/(123)I SPECT. In GSFA, the energy spectrum of the photons in any pixel is expressed as a linear combination of five common spectra: (99m)Tc and (123)I photopeaks and three scatter spectra. These basis spectra are estimated from a factor analysis of all spectra using physical priors (e.g. Klein-Nishina distributions). GSFA was evaluated on (99m)Tc/(123)I Monte Carlo simulated data and compared to images obtained using recommended spectral windows (WIN) and to the gold standard (GS) images (scatter-free, cross-talk-free and noise-free). Using GSFA, activity concentration differed by less than 9% compared to GS values against differences from -23% to 110% with WIN in the (123)I and (99m)Tc images respectively. Using GSFA, simultaneous (99m)Tc/(123)I imaging can yield images of similar quantitative accuracy as when using sequential and scatter-free (99m)Tc/(123)I imaging in brain SPECT.     

Acceleration of Monte Carlo-based scatter compensation for cardiac SPECT

Single proton emission computed tomography (SPECT) images are degraded by photon scatter making scatter compensation essential for accurate reconstruction. Reconstruction-based scatter compensation with Monte Carlo (MC) modelling of scatter shows promise for accurate scatter correction, but it is normally hampered by long computation times. The aim of this work was to accelerate the MC-based scatter compensation using coarse grid and intermittent scatter modelling. The acceleration methods were compared to un-accelerated implementation using MC-simulated projection data of the mathematical cardiac torso (MCAT) phantom modelling (99m)Tc uptake and clinical myocardial perfusion studies. The results showed that when combined the acceleration methods reduced the reconstruction time for 10 ordered subset expectation maximization (OS-EM) iterations from 56 to 11 min without a significant reduction in image quality indicating that the coarse grid and intermittent scatter modelling are suitable for MC-based scatter compensation in cardiac SPECT.     

Model-based crosstalk compensation for simultaneous 99mTc/123I dual-isotope brain SPECT imaging

In this work, we developed a model-based method to estimate and compensate for the crosstalk contamination in simultaneous 123I and 99mTc dual isotope brain single photo emission computed tomography imaging. The model-based crosstalk compensation (MBCC) includes detailed modeling of photon interactions inside both the object and the detector system. In the method, scatter in the object is modeled using the effective source scatter estimation technique, including contributions from all the photon emissions. The effects of the collimator-detector response, including the penetration and scatter components due to high-energy 123I photons, are modeled using precalculated tables of Monte Carlo simulated point-source response functions obtained from sources in air at various distances from the face of the collimator. The model-based crosstalk estimation method was combined with iterative reconstruction based compensation to reduce contamination due to crosstalk. The MBCC method was evaluated using Monte Carlo simulated and physical phantom experimentally acquired simultaneous dual-isotope data. Results showed that, for both experimental and simulation studies, the model-based method provided crosstalk estimates that were in good agreement with the true crosstalk. Compensation using MBCC improved image contrast and removed the artifacts for both Monte Carlo simulated and experimentally acquired data. The results were in good agreement with images acquired without any crosstalk contamination.     

Model-based compensation for quantitative 123I brain SPECT imaging

Previously we have developed a model-based method that can accurately estimate downscatter contamination from high-energy photons in 123I imaging. In this work we combined the model-based method with iterative reconstruction-based compensations for other image-degrading factors such as attenuation, scatter, the collimator-detector response function (CDRF) and partial volume effects to form a comprehensive method for performing quantitative 123I SPECT image reconstruction. In the model-based downscatter estimation method, photon scatter inside the object was modelled using the effective source scatter estimation (ESSE) technique, including contributions from all the photon emissions. The CDRFs, including the penetration and scatter components due to the high-energy 123I photons, were estimated using Monte Carlo (MC) simulations of point sources in air at various distances from the face of the collimator. The downscatter contamination was then compensated for during the iterative reconstruction by adding the estimated results to the projection steps. The model-based downscatter compensation (MBDC) was evaluated using MC simulated and experimentally acquired projection data. From the MC simulation, we found about 39% of the total counts in the energy window of 123I were attributed to the downscatter contamination, which reduced image contrast and caused a 1.5% to 10% overestimation of activities in various brain structures. Model-based estimates of the downscatter contamination were in good agreement with the simulated data. Compensation using MBDC removed the contamination and improved the image contrast and quantitative accuracy to that of the images obtained from 159 keV photons. The errors in absolute quantitation were reduced to within +/-3.5%. The striatal specific binding potential calculated based on the activity ratio to the background was also improved after MBDC. The errors were reduced from -4.5% to -10.93% without compensation to -0.55% to 4.87% after compensation. The model-based method provided accurate downscatter estimation and, when combined with iterative reconstruction-based compensations, accurate quantitation was obtained with minimal loss of precision.     

Implementation of an iterative scatter correction, the influence of attenuation map quality and their effect on absolute quantitation in SPECT

We investigated the accuracy of qSPECT, a quantitative SPECT reconstruction algorithm we have developed which employs corrections for collimator blurring, photon attenuation and scatter, and provides images in units of absolute radiotracer concentrations (kBq cm(-3)). Using simulated and experimental phantom data with characteristics similar to clinical cardiac perfusion data, we studied the implementation of a scatter correction (SC) as part of an iterative reconstruction protocol. Additionally, with experimental phantom studies we examined the influence of CT-based attenuation maps, relative to those obtained from conventional SPECT transmission scans, on SCs and quantitation. Our results indicate that the qSPECT estimated scatter corrections did not change appreciably after the third iteration of the reconstruction. For the simulated data, qSPECT concentrations agreed with images reconstructed using ideal, scatter-free, simulated data to within 6%. For the experimental data, we observed small systematic differences in the scatter fractions for data using different combinations of SCs and attenuation maps. The SCs were found to be significantly influenced by errors in image coregistration. The reconstructed concentrations using CT-based corrections were more quantitatively accurate than those using attenuation maps from conventional SPECT transmission scans. However, segmenting the attenuation maps from SPECT transmission scans could provide sufficient accuracy for most applications.     

The influence of backscatter material on 99mTc and 201Tl line source responses

SPECT projections are contaminated by scatter, resulting in reduced image contrast and quantitative errors. When tissue is present behind the source, some of the detected photons backscatter via this tissue. Particularly in dual-isotope SPECT and in combined emission-transmission SPECT, backscatter constitutes a major part of the down-scatter contamination in lower-energy windows. In this paper, the effects of backscatter material were investigated. Planar images of 99mTc and 201Tl line sources between varying numbers of Perspex slabs were analysed using the photopeak windows and various scatter windows. In the 99mTc photopeak window no significant change in total counts due to backscatter material was measured. In the 201Tl photopeak window an increase of about 10% in total counts was observed. In the scatter windows an even more explicit influence of backscatter material was measured. For instance, at a forward depth of 10 cm, total counts of a 99mTc source detected in the 72 keV window eventually doubled with increasing backscatter material, compared with the situation without backscatter material. The backscatter contribution plateaued when more than 5-10 cm of scatter material was placed behind the source. In conclusion, backscatter should be taken into account, particularly in model-based down-scatter correction methods in dual-isotope SPECT and combined emission-transmission SPECT.     

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.     

Testing of local gamma-ray scatter fractions determined by spectral fitting

The spectral-fitting method of correction for gamma-ray Compton scattering within objects separates the unscattered and scattered components of locally measured energy spectra. Here, we employ a third-order polynomial for the scattering and an approximately constant fitting window. A scatter fraction, defined as total scattered over total unscattered counts within a 20% window, is calculated for each point in our Anger camera images. These scatter fractions are tested against those from Monte-Carlo simulation for 99mTc and against results from semiconductor detector measurements for 131I. A radioactive sphere at several locations within a non-radioactive cylinder and the inverse are imaged for the testing. For one case, reproducibility of the spectral-fitting scatter fraction as a function of the number of unscattered counts within the 20% acceptance window was also determined. With 99mTc, for all cases, the agreement between spectral fitting and the standard estimation method is within 16%. With 131I, for the 'hot' sphere at two locations, the agreement is within 21%. For the 'hot' sphere at the third location (off the cylinder axis towards the camera), the dependence of scatter fraction on transverse distance is good although the absolute values are too large. Scatter fraction reproducibility is within 10% for 1000 or more counts. Therefore, further testing of spectral fitting and initial application to realistic clinical images seem to be in order.     

Accuracy of quantitative reconstructions in SPECT/CT imaging

The goal of this study was to determine the quantitative accuracy of our OSEM-APDI reconstruction method based on SPECT/CT imaging for Tc-99m, In-111, I-123, and I-131 isotopes. Phantom studies were performed on a SPECT/low-dose multislice CT system (Infinia-Hawkeye-4 slice, GE Healthcare) using clinical acquisition protocols. Two radioactive sources were centrally and peripherally placed inside an anthropometric Thorax phantom filled with non-radioactive water. Corrections for attenuation, scatter, collimator blurring and collimator septal penetration were applied and their contribution to the overall accuracy of the reconstruction was evaluated. Reconstruction with the most comprehensive set of corrections resulted in activity estimation with error levels of 3-5% for all the isotopes.     

An iterative transmission algorithm incorporating cross-talk correction for SPECT

Simultaneous emission/transmission acquisitions in cardiac SPECT with a Tc99m/Gd153 source combination offer the capability for nonuniform attenuation correction. However, cross-talk of Tc99m photons downscattered into the Gd153 energy window contaminates the reconstructed transmission map used for attenuation correction. The estimated cross-talk contribution can be subtracted prior to transmission reconstruction or incorporated in the reconstruction algorithm itself. In this work, we propose an iterative transmission algorithm (MLTG-S) based on the maximum-likelihood gradient algorithm (MLTG) that explicitly accounts for this cross-talk estimate. Clinical images were acquired on a three-headed SPECT camera, acquiring Tc99m emission and Gd153 transmission images simultaneously. Subtracting the cross-talk estimate prior to transmission reconstruction can result in negative and zero values if the estimate is larger than or equal to the count in the transmission projection bin, especially with increased attenuator size or amount of cross-talk. This results in inaccurate attenuation coefficients for MLTG reconstructions with cross-talk subtraction. MLTG-S reconstructions on the other hand, yield better estimates of attenuation maps, by avoiding the subtraction of the cross-talk estimate. Comparison of emission slices corrected for nonuniform attenuation reveals that inaccuracies in the reconstructed attenuation map caused by cross-talk can artificially enhance the extra-cardiac activity, confounding the ability to visualize the left-ventricular walls.     

Temporal lobe asymmetry with iofetamine (IMP) SPECT imaging in patients with major depression.

Single photon emission computed tomography (SPECT) brain imaging with 123I labeled iofetamine (IMP) has been used to study several neuropsychiatric disorders. However, little attention has been given to patients with major depression. In the present study IMP SPECT images were obtained on 19 depressed patients and 12 medical comparison subjects who had no focal abnormalities on MRI or CT scans. 5 mCi of 123I IMP was administered intravenously and SPECT images were obtained using a GE Starcamm 2000 SPECT system. After standard reconstruction of the images, an automated region of interest (ROI) computer program was applied to each tomographic brain image. Coronal images were then used to analyze lateralized differences in IMP activity. Measurements were made of the mean IMP activity per pixel, the maximum activity per pixel, and the ratio of the mean activity per pixel in the ROI to that of the cerebellum. On visual inspection, 12 out of 19 depressed patients (63%) and only of 12 medical comparison patients (8%) appeared to have substantially increased IMP activity in the right temporal lobe (P less than 0.005). But semi-quantitative analysis showed that while IMP activity was greater in the right than the left temporal lobe of depressed patients (P less than 0.0001), it was also present in medical comparison patients (P less than 0.01). Although there was no difference in the frequency of asymmetry between groups, it was more pronounced in depressed patients. These data suggest that asymmetric temporal lobe activity on IMP SPECT images may be of potential diagnostic utility in some patients with affective disorders.     

Quantitative pulmonary single photon emission computed tomography for radiotherapy applications.

Pulmonary imaging using single photon emission computed tomography (SPECT) is the focus of current radiotherapy research, including dose-response analysis and three-dimensional (3D) radiation treatment planning. Improvement in the quantitative capability of SPECT may help establish its potential role in this application as well as others requiring accurate knowledge of pulmonary blood flow. The purposes of this study were to quantitatively evaluate SPECT filtered backprojection (FBP) and ordered subset-expectation maximization (OS-EM) reconstruction implementations for measuring absolute activity concentration in lung phantom experiments, and to incorporate quantitative SPECT techniques in 3D-RTP for lung cancer. Quantitative FBP (nonuniform iterative Chang attenuation compensation, scatter correction, and 3D postreconstruction Metz filtering) and OS-EM implementations were compared with a "clinical" implementation of FBP (uniform multiplicative Chang attenuation compensation and post-reconstruction von Hann filtering), for their ability to improve quantification of inactive and active spherical defects in the lungs of an anthropomorphic torso phantom. Activity concentration estimates were found to depend on many factors, such as region of interest size, scatter subtraction constant (k), postreconstruction deconvolution filtering and, in the case of OS-EM, total number of iterations. In general, reconstruction implementations incorporating compensation for nonuniform attenuation and scatter provided reduced bias relative to the clinical implementation. Potential applications to lung radiotherapy, including dose-functional histograms and treatment planning are also discussed. SPECT has the potential to provide accurate estimates of lung activity distributions that, together with improved image quality, may be useful for the study and prediction of therapeutic response.     

Gaussian prefiltering of 123I DAT SPECT images when using depth-independent resolution recovery

Previously we have investigated a depth-independent compensation for collimator detector response (CDR) included in the OSEM reconstruction, intended for SPECT images that have been corrected for scatter and septal penetration using convolution-based methods. In this work, the aim was to study how different filtering strategies affect contrast as a function of noise when using Gaussian smoothing filters in combination with the above-described CDR compensation. The evaluation was performed for (123)I dopamine transporter (DAT) SPECT images. Prefiltering with 2D Gaussian filter kernels, where the deterioration in resolution is included in the depth-independent CDR compensation, was compared to conventional postfiltering with 3D Gaussian filter kernels. Images reconstructed without filtering are also included in the comparison. It was found that there is little benefit in noise reduction when using CDR compensation. However, this variant of prefiltering gives consistently higher contrasts as a function of noise compared with the postfiltering alternative, and that could be of interest when using other types of filters with contrast improving properties.     

Monte Carlo simulations of clinical PET and SPECT scans: impact of the input data on the simulated images

Monte Carlo simulations of emission tomography have proven useful to assist detector design and optimize acquisition and processing protocols. The more realistic the simulations, the more straightforward the extrapolation of conclusions to clinical situations. In emission tomography, accurate numerical models of tomographs have been described and well validated under specific operating conditions (collimator, radionuclide, acquisition parameters, count rates, etc). When using these models under these operating conditions, the realism of simulations mostly depends on the activity distribution used as an input for the simulations. It has been proposed to derive the input activity distribution directly from reconstructed clinical images, so as to properly model the heterogeneity of the activity distribution between and within organs. However, reconstructed patient images include noise and have limited spatial resolution. In this study, we analyse the properties of the simulated images as a function of the properties of the reconstructed images used to define the input activity distributions in (18)F-FDG PET and (131)I SPECT simulations. The propagation through the simulation/reconstruction process of the noise and spatial resolution in the input activity distribution was studied using simulations. We found that the noise properties of the images reconstructed from the simulated data were almost independent of the noise in the input activity distribution. The spatial resolution in the images reconstructed from the simulations was slightly poorer than that in the input activity distribution. However, using high-noise but high-resolution patient images as an input activity distribution yielded reconstructed images that could not be distinguished from clinical images. These findings were confirmed by simulated highly realistic (131)I SPECT and (18)F-FDG PET images from patient data. In conclusion, we demonstrated that (131)I SPECT and (18)F-FDG PET images indistinguishable from real scans can be simulated using activity maps with spatial resolution higher than that used in routine clinical applications.     

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.     

Generalized dual-energy-window scatter compensation in spatially varying media for SPECT

The detection of scattered photons in the photopeak energy window hinders accurate activity estimation in single-photon-emission computed tomography (SPECT). To compensate for photons scattered in spatially varying media, a framework for generalized dual-energy-window scatter subtraction has been developed. Generalized scatter subtraction factors are introduced, and these factors are decomposed into terms dependent on the uniform (average) and spatially varying components of the source activity distribution. The variation of these factors with projection pixel location and gamma camera position is analysed for a simulated myocardial perfusion study with a 99Tc(m) source radionuclide and a non-uniform thorax model. Monte Carlo methods are used to model photon transport and detection. The application of pixel-dependent scatter subtraction factors for scatter compensation is evaluated in an image reconstruction experiment for this simulated myocardial perfusion study. Generalized matrix inverses with noise-dependent regularization are used for image reconstruction. For this simulation, use of a pixel-dependent scatter subtraction factor and a constant scatter subtraction factor are effective for scatter compensation. Activity estimates within the left ventricular myocardium for these two methods are practically the same as those obtained from image reconstructions where the detection of Compton-scattered photons is included in the system matrix.     

Analytical propagation of errors in dynamic SPECT: estimators, degrading factors, bias and noise.

Dynamic SPECT is a relatively new technique that may potentially benefit many imaging applications. Though similar to dynamic PET, the accuracy and precision of dynamic SPECT parameter estimates are degraded by factors that differ from those encountered in PET. In this work we formulate a methodology for analytically studying the propagation of errors from dynamic projection data to kinetic parameter estimates. This methodology is used to study the relationships between reconstruction estimators, image degrading factors, bias and statistical noise for the application of dynamic cardiac imaging with 99mTc-teboroxime. Dynamic data were simulated for a torso phantom, and the effects of attenuation, detector response and scatter were successively included to produce several data sets. The data were reconstructed to obtain both weighted and unweighted least squares solutions, and the kinetic rate parameters for a two-compartment model were estimated. The expected values and standard deviations describing the statistical distribution of parameters that would be estimated from noisy data were calculated analytically. The results of this analysis present several interesting implications for dynamic SPECT. Statistically weighted estimators performed only marginally better than unweighted ones, implying that more computationally efficient unweighted estimators may be appropriate. This also suggests that it may be beneficial to focus future research efforts upon regularization methods with beneficial bias-variance trade-offs. Other aspects of the study describe the fundamental limits of the bias variance trade-off regarding physical degrading factors and their compensation. The results characterize the effects of attenuation, detector response and scatter, and they are intended to guide future research into dynamic SPECT reconstruction and compensation methods.