Body morphometry appropriate computational phantoms for dose and risk optimization in pediatric renal imaging with Tc-99m DMSA and Tc-99m MAG3.

Current guidelines for administered activity (AA) in pediatric nuclear medicine imaging studies are based on a 2016 harmonization of the 2010 North American Consensus guidelines and the 2007 European Association of Nuclear Medicine pediatric dosage card. These guidelines assign AA scaled to patient body mass, with further constraints on maximum and minimum values of radiopharmaceutical activity. These guidelines, however, are not formulated based upon a rigor-ous evaluation of diagnostic image quality. In a recent study of the renal cortex imaging agent 99mTc-DMSA (Li Y et al 2019), body mass-based dosing guidelines were shown to not give the same level of image quality for patients of differing body mass. Their data suggest that patient girth at the level of the kidneys may be a better morphometric parameter to consider when selecting AA for renal nuclear medicine imaging. The objective of the present work was thus to develop a dedicated series of computational phantoms to support image quality and organ dose studies in pediatric renal imaging using 99mTc-DMSA or 99mTc-MAG3. The final library consists of 50 male and female phantoms of ages 0 to 15 years, with percentile variations (5th to 95th) in waist circumference (WC) at each age. For each phantom, nominal values of kidney volume, length, and depth were incorporated into the phantom design. Organ absorbed doses, detriment-weighted doses, and stochastic risks were assessed using ICRP reference biokinetic models for both agents. In Monte Carlo radiation transport simulations, organ doses for these agents yielded detriment-weighted dose coefficients (mSv/MBq) that were in general larger than current ICRP values of the effective dose coefficients (age and WC-averaged ratios of eDW/e were 1.40 for the male phantoms and 1.49 for the female phantoms). Values of risk index (ratio of radiation-induced to natural background cancer incidence risk x 100) varied between 0.062 (newborns) to 0.108 (15-year-olds) for 99mTc-DMSA and between 0.026 (newborns) to 0.122 (15-year-olds) for 99mTc-MAG3. Using tallies of photon exit fluence as a rough surrogate for uniform image quality, our study demonstrated that through body region-of-interest optimization of AA, there is the potential for further dose and risk reductions of between factors of 1.5 to 3.0 beyond simple weight-based dosing guidance.

Specific absorbed fractions and radionuclide S-values for tumors of varying size and composition.

Accurate estimates of tumor absorbed dose are essential for the evaluation of treatment efficacy in radiopharmaceutical cancer therapy. Although tumor dosimetry via the MIRD schema has been previously investigated, prior studies have been limited to the consideration of soft-tissue tumors. In the present study, specific absorbed fractions (SAFs) for monoenergetic photons, electrons, and alpha particles in tumors of varying compositions were computed using Monte Carlo simulations in MCNPX after which self-irradiation S-values for 22 radionuclides (along with 14 additional alpha-emitter progeny) were generated for tumors of both varying size and tissue composition. The tumors were modeled as spheres with radii ranging from 0.10 cm to 6.0 cm and with compositions varying from 100% soft tissue (ST) to 100% mineral bone (MB). The energies of the photons and electrons were varied on a logarithm energy grid from 10 keV to 10 MeV. The energies of alpha particles were varied along a linear energy grid from 0.5 MeV to 12 MeV. In all cases, a homogenous activity distribution was assumed throughout the tumor volume. Furthermore, to assess the effect of tumor shape, several ellipsoidal tumors of different compositions were modeled and absorbed fractions were computed for monoenergetic electrons and photons. S-values were then generated using detailed decay data from the 2008 MIRD Monograph on Radionuclide Data and Decay Schemes. Our study results demonstrate that a soft-tissue model yields relative errors of 25% and 71% in the absorbed fraction assigned to uniform sources of 1.5 MeV electrons and 100 keV photons, respectively, localized within a 1 cm diameter tumor of MB. The data further show that absorbed fractions for moderate ellipsoids can be well approximated by a spherical shape of equal mass within a relative error of < 8%. S-values for 22 radionuclides (and their daughter progeny) were computed with results demonstrating how relative errors in SAFs could propagate to relative errors in tumor dose estimates as high as 86%. A comprehensive data set of radionuclide S-values by tumor size and tissue composition is provided for application of the MIRD schema for tumor dosimetry in radiopharmaceutical therapy.

The effect of attenuation map, scatter energy window width, and volume of interest on the calibration factor calculation in quantitative 177Lu SPECT imaging: Simulation and phantom study.

PURPOSE: The objective of this study was to evaluate the image degrading factors in quantitative 177Lu SPECT imaging when using both main gamma photopeak energies. METHODS: Phantom measurements with two different vials containing various calibrated activities in air or water were performed to derive a mean calibration factor (CF) for large and small volumes of interest (VOIs). In addition, Monte Carlo simulations were utilized to investigate the effect of scatter energy window width, scatter correction method, such as effective scatter source estimation (ESSE) and triple energy window (TEW), and attenuation map on the quantification of 177Lu. RESULTS: The measured mean CF using large and small VOIs in water was 4.50 ±â€¯0.80 and 4.80 ±â€¯0.72 cps MBq-1, respectively. Simulations showed a reference CF of 3.3 cps MBq-1 for the water-filled phantom considering all photons excluding scattered events. By using the attenuation map generated for 190 keV photons, the calculated CFs for 113 keV and 208 keV are 10% lower than by using the weighted mean energy of 175 keV for 177Lu. The calculated CF using the TEW correction was 17% higher than using the ESSE method for a water-filled phantom. However, our findings showed that an appropriate scatter window combination can reduce this difference between TEW and ESSE methods. CONCLUSIONS: The present work implies that choosing a suitable width of scatter energy windows can reduce uncertainties in radioactivity quantification. It is suggested to generate the attenuation map at 113 keV and 208 keV, separately. Furthermore, using small VOIs is suggested in CF calculation.

Simplifying volumes-of-interest (VOIs) definition in quantitative SPECT: Beyond manual definition of 3D whole-organ VOIs.

PURPOSE: We investigated the feasibility of using simpler methods than manual whole-organ volume-of-interest (VOI) definition to estimate the organ activity concentration in single photon emission computed tomography (SPECT) in cases where the activity in the organ can be assumed to be uniformly distributed on the scale of the voxel size. In particular, we investigated an anatomic region-of-interest (ROI) defined in a single transaxial slice, and a single sphere placed inside the organ boundaries. METHODS: The evaluation was carried out using Monte Carlo simulations based on patient indium 111 In pentetreotide SPECT and computed tomography (CT) images. We modeled constant activity concentrations in each organ, validating this assumption by comparing the distribution of voxel values inside the organ VOIs of the simulated data with the patient data. We simulated projection data corresponding to 100, 50, and 25% of the clinical count level to study the effects of noise level due to shortened acquisition time. Images were reconstructed using a previously validated quantitative SPECT reconstruction method. The evaluation was performed in terms of the accuracy and precision of the activity concentration estimates. RESULTS: The results demonstrated that the non-uniform image intensity observed in the reconstructed images in the organs with normal uptake was consistent with uniform activity concentration in the organs on the scale of the voxel size; observed non-uniformities in image intensity were due to a combination of partial-volume effects at the boundaries of the organ, artifacts in the reconstructed image due to collimator-detector response compensation, and noise. Using an ROI defined in a single transaxial slice produced similar biases compared to the three-dimensional (3D) whole-organ VOIs, provided that the transaxial slice was near the central plane of the organ and that the pixels from the organ boundaries were not included in the ROI. Although this slice method was sensitive to noise, biases were less than 10% for all the noise levels studied. The use of spherical VOIs was more sensitive to noise. The method was more accurate for larger spheres and larger organs such as the liver in comparison to the kidneys. Biases lower than 7% were found in the liver when using large enough spheres (radius ≥ 28 mm), regardless of the position, of the VOI inside the organ even with shortened acquisition times. The biases were more position-dependent for smaller organs. CONCLUSIONS: Both of the simpler methods provided suitable surrogates in terms of accuracy and precision. The results suggested that a spherical VOI was more appropriate for estimating the activity concentration in larger organs such as the liver, regardless of the position of the sphere inside the organ. Larger spheres resulted in better estimates. A single-slice ROI was more suitable for activity estimation in smaller organs such as the kidneys, providing that the transaxial slice selected was near the central plane of the organ and that voxels from the organ boundaries were excluded. Under those conditions, activity concentrations with biases lower than 5% were observed for all the studied count levels and coefficients of variation were less than 9% and 5% for the 25% and 100% count levels, respectively.

A no-gold-standard technique for objective assessment of quantitative nuclear-medicine imaging methods.

The objective optimization and evaluation of nuclear-medicine quantitative imaging methods using patient data is highly desirable but often hindered by the lack of a gold standard. Previously, a regression-without-truth (RWT) approach has been proposed for evaluating quantitative imaging methods in the absence of a gold standard, but this approach implicitly assumes that bounds on the distribution of true values are known. Several quantitative imaging methods in nuclear-medicine imaging measure parameters where these bounds are not known, such as the activity concentration in an organ or the volume of a tumor. We extended upon the RWT approach to develop a no-gold-standard (NGS) technique for objectively evaluating such quantitative nuclear-medicine imaging methods with patient data in the absence of any ground truth. Using the parameters estimated with the NGS technique, a figure of merit, the noise-to-slope ratio (NSR), can be computed, which can rank the methods on the basis of precision. An issue with NGS evaluation techniques is the requirement of a large number of patient studies. To reduce this requirement, the proposed method explored the use of multiple quantitative measurements from the same patient, such as the activity concentration values from different organs in the same patient. The proposed technique was evaluated using rigorous numerical experiments and using data from realistic simulation studies. The numerical experiments demonstrated that the NSR was estimated accurately using the proposed NGS technique when the bounds on the distribution of true values were not precisely known, thus serving as a very reliable metric for ranking the methods on the basis of precision. In the realistic simulation study, the NGS technique was used to rank reconstruction methods for quantitative single-photon emission computed tomography (SPECT) based on their performance on the task of estimating the mean activity concentration within a known volume of interest. Results showed that the proposed technique provided accurate ranking of the reconstruction methods for 97.5% of the 50 noise realizations. Further, the technique was robust to the choice of evaluated reconstruction methods. The simulation study pointed to possible violations of the assumptions made in the NGS technique under clinical scenarios. However, numerical experiments indicated that the NGS technique was robust in ranking methods even when there was some degree of such violation.

Optimization and comparison of simultaneous and separate acquisition protocols for dual isotope myocardial perfusion SPECT.

Dual-isotope simultaneous-acquisition (DISA) rest-stress myocardial perfusion SPECT (MPS) protocols offer a number of advantages over separate acquisition. However, crosstalk contamination due to scatter in the patient and interactions in the collimator degrade image quality. Compensation can reduce the effects of crosstalk, but does not entirely eliminate image degradations. Optimizing acquisition parameters could further reduce the impact of crosstalk. In this paper we investigate the optimization of the rest Tl-201 energy window width and relative injected activities using the ideal observer (IO), a realistic digital phantom population and Monte Carlo (MC) simulated Tc-99m and Tl-201 projections as a means to improve image quality. We compared performance on a perfusion defect detection task for Tl-201 acquisition energy window widths varying from 4 to 40 keV centered at 72 keV for a camera with a 9% energy resolution. We also investigated 7 different relative injected activities, defined as the ratio of Tc-99m and Tl-201 activities, while keeping the total effective dose constant at 13.5 mSv. For each energy window and relative injected activity, we computed the IO test statistics using a Markov chain Monte Carlo (MCMC) method for an ensemble of 1,620 triplets of fixed and reversible defect-present, and defect-absent noisy images modeling realistic background variations. The volume under the 3-class receiver operating characteristic (ROC) surface (VUS) was estimated and served as the figure of merit. For simultaneous acquisition, the IO suggested that relative Tc-to-Tl injected activity ratios of 2.6-5 and acquisition energy window widths of 16-22% were optimal. For separate acquisition, we observed a broad range of optimal relative injected activities from 2.6 to 12.1 and acquisition energy window of widths 16-22%. A negative correlation between Tl-201 injected activity and the width of the Tl-201 energy window was observed in these ranges. The results also suggested that DISA methods could potentially provide image quality as good as that obtained with separate acquisition protocols. We compared observer performance for the optimized protocols and the current clinical protocol using separate acquisition. The current clinical protocols provided better performance at a cost of injecting the patient with approximately double the injected activity of Tc-99m and Tl-201, resulting in substantially increased radiation dose.

Development and evaluation of convergent and accelerated penalized SPECT image reconstruction methods for improved dose-volume histogram estimation in radiopharmaceutical therapy.

PURPOSE: Three-dimensional (3D) dosimetry has the potential to provide better prediction of response of normal tissues and tumors and is based on 3D estimates of the activity distribution in the patient obtained from emission tomography. Dose-volume histograms (DVHs) are an important summary measure of 3D dosimetry and a widely used tool for treatment planning in radiation therapy. Accurate estimates of the radioactivity distribution in space and time are desirable for accurate 3D dosimetry. The purpose of this work was to develop and demonstrate the potential of penalized SPECT image reconstruction methods to improve DVHs estimates obtained from 3D dosimetry methods. METHODS: The authors developed penalized image reconstruction methods, using maximum a posteriori (MAP) formalism, which intrinsically incorporate regularization in order to control noise and, unlike linear filters, are designed to retain sharp edges. Two priors were studied: one is a 3D hyperbolic prior, termed single-time MAP (STMAP), and the second is a 4D hyperbolic prior, termed cross-time MAP (CTMAP), using both the spatial and temporal information to control noise. The CTMAP method assumed perfect registration between the estimated activity distributions and projection datasets from the different time points. Accelerated and convergent algorithms were derived and implemented. A modified NURBS-based cardiac-torso phantom with a multicompartment kidney model and organ activities and parameters derived from clinical studies were used in a Monte Carlo simulation study to evaluate the methods. Cumulative dose-rate volume histograms (CDRVHs) and cumulative DVHs (CDVHs) obtained from the phantom and from SPECT images reconstructed with both the penalized algorithms and OS-EM were calculated and compared both qualitatively and quantitatively. The STMAP method was applied to patient data and CDRVHs obtained with STMAP and OS-EM were compared qualitatively. RESULTS: The results showed that the penalized algorithms substantially improved the CDRVH and CDVH estimates for large organs such as the liver compared to optimally postfiltered OS-EM. For example, the mean squared errors (MSEs) of the CDRVHs for the liver at 5 h postinjection obtained with CTMAP and STMAP were about 15% and 17%, respectively, of the MSEs obtained with optimally filtered OS-EM. For the CDVH estimates, the MSEs obtained with CTMAP and STMAP were about 16% and 19%, respectively, of the MSEs from OS-EM. For the kidneys and renal cortices, larger residual errors were observed for all algorithms, likely due to partial volume effects. The STMAP method showed promising qualitative results when applied to patient data. CONCLUSIONS: Penalized image reconstruction methods were developed and evaluated through a simulation study. The study showed that the MAP algorithms substantially improved CDVH estimates for large organs such as the liver compared to optimally postfiltered OS-EM reconstructions. For small organs with fine structural detail such as the kidneys, a large residual error was observed for both MAP algorithms and OS-EM. While CTMAP provided marginally better MSEs than STMAP, given the extra effort needed to handle misregistration of images at different time points in the algorithm and the potential impact of residual misregistration, 3D regularization methods, such as that used in STMAP, appear to be a more practical choice.

Design of a digital phantom population for myocardial perfusion SPECT imaging research.

Digital phantoms and Monte Carlo (MC) simulations have become important tools for optimizing and evaluating instrumentation, acquisition and processing methods for myocardial perfusion SPECT (MPS). In this work, we designed a new adult digital phantom population and generated corresponding Tc-99m and Tl-201 projections for use in MPS research. The population is based on the three-dimensional XCAT phantom with organ parameters sampled from the Emory PET Torso Model Database. Phantoms included three variations each in body size, heart size, and subcutaneous adipose tissue level, for a total of 27 phantoms of each gender. The SimSET MC code and angular response functions were used to model interactions in the body and the collimator-detector system, respectively. We divided each phantom into seven organs, each simulated separately, allowing use of post-simulation summing to efficiently model uptake variations. Also, we adapted and used a criterion based on the relative Poisson effective count level to determine the required number of simulated photons for each simulated organ. This technique provided a quantitative estimate of the true noise in the simulated projection data, including residual MC simulation noise. Projections were generated in 1 keV wide energy windows from 48-184 keV assuming perfect energy resolution to permit study of the effects of window width, energy resolution, and crosstalk in the context of dual isotope MPS. We have developed a comprehensive method for efficiently simulating realistic projections for a realistic population of phantoms in the context of MPS imaging. The new phantom population and realistic database of simulated projections will be useful in performing mathematical and human observer studies to evaluate various acquisition and processing methods such as optimizing the energy window width, investigating the effect of energy resolution on image quality and evaluating compensation methods for degrading factors such as crosstalk in the context of single and dual isotope MPS.

Simultaneous Tc-99m/I-123 dual-radionuclide myocardial perfusion/innervation imaging using Siemens IQ-SPECT with SMARTZOOM collimator.

Simultaneous dual-radionuclide myocardial perfusion/innervation SPECT imaging can provide important information about the mismatch between scar tissue and denervated regions. The Siemens IQ-SPECT system developed for cardiac imaging uses a multifocal SMARTZOOM collimator to achieve a four-fold sensitivity for the cardiac region, compared to a typical parallel-hole low-energy high-resolution collimator, but without the data truncation that can result with conventional converging-beam collimators. The increased sensitivity allows shorter image acquisition times or reduced patient dose, making IQ-SPECT ideal for simultaneous dual-radionuclide SPECT, where reduced administrated activity is desirable in order to reduce patient radiation exposure. However, crosstalk is a major factor affecting the image quality in dual-radionuclide imaging. In this work we developed a model-based method that can estimate and compensate for the crosstalk in IQ-SPECT data. The crosstalk model takes into account interactions in the object and collimator-detector system. Scatter in the object was modeled using the effective source scatter estimation technique (ESSE), previously developed to model scatter with parallel-hole collimators. The geometric collimator-detector response was analytically modeled in the IQ-SPECT projector. The estimated crosstalk was then compensated for in an iterative reconstruction process. The new method was validated with data from both Monte Carlo simulations and physical phantom experiments. The results showed that the estimated crosstalk was in good agreement with simulated and measured results. After model-based compensation the images from simultaneous dual-radionuclide acquisitions were similar in quality to those from single-radionuclide acquisitions that did not have crosstalk contamination. The proposed model-based method can be used to improve simultaneous dual-radionuclide images acquired using IQ-SPECT. This work also demonstrates that ESSE scatter modeling can be applied to non-parallel-beam projection geometries.

Improved dose-volume histogram estimates for radiopharmaceutical therapy by optimizing quantitative SPECT reconstruction parameters.

In radiopharmaceutical therapy, an understanding of the dose distribution in normal and target tissues is important for optimizing treatment. Three-dimensional (3D) dosimetry takes into account patient anatomy and the nonuniform uptake of radiopharmaceuticals in tissues. Dose-volume histograms (DVHs) provide a useful summary representation of the 3D dose distribution and have been widely used for external beam treatment planning. Reliable 3D dosimetry requires an accurate 3D radioactivity distribution as the input. However, activity distribution estimates from SPECT are corrupted by noise and partial volume effects (PVEs). In this work, we systematically investigated OS-EM based quantitative SPECT (QSPECT) image reconstruction in terms of its effect on DVHs estimates. A modified 3D NURBS-based Cardiac-Torso (NCAT) phantom that incorporated a non-uniform kidney model and clinically realistic organ activities and biokinetics was used. Projections were generated using a Monte Carlo (MC) simulation; noise effects were studied using 50 noise realizations with clinical count levels. Activity images were reconstructed using QSPECT with compensation for attenuation, scatter and collimator-detector response (CDR). Dose rate distributions were estimated by convolution of the activity image with a voxel S kernel. Cumulative DVHs were calculated from the phantom and QSPECT images and compared both qualitatively and quantitatively. We found that noise, PVEs, and ringing artifacts due to CDR compensation all degraded histogram estimates. Low-pass filtering and early termination of the iterative process were needed to reduce the effects of noise and ringing artifacts on DVHs, but resulted in increased degradations due to PVEs. Large objects with few features, such as the liver, had more accurate histogram estimates and required fewer iterations and more smoothing for optimal results. Smaller objects with fine details, such as the kidneys, required more iterations and less smoothing at early time points post-radiopharmaceutical administration but more smoothing and fewer iterations at later time points when the total organ activity was lower. The results of this study demonstrate the importance of using optimal reconstruction and regularization parameters. Optimal results were obtained with different parameters at each time point, but using a single set of parameters for all time points produced near-optimal dose-volume histograms.

Compensation for spill-in and spill-out partial volume effects in cardiac PET imaging.

BACKGROUND: Partial volume effects (PVEs) in PET imaging result in incorrect regional activity estimates due to both spill-out and spill-in from activity in neighboring regions. It is important to compensate for both effects to achieve accurate quantification. In this study, an image-based partial volume compensation (PVC) method was developed and validated for cardiac PET. METHODS AND RESULTS: The method uses volume-of-interest (VOI) maps segmented from contrast-enhanced CTA images to compensate for both spill-in and spill-out in each VOI. The PVC method was validated with simulation studies and also applied to images of dog cardiac perfusion PET data. The PV effects resulting from cardiac motion and myocardial uptake defects were investigated and the efficacy of the proposed PVC method in compensating for these effects was evaluated. RESULTS: Results indicate that the magnitude and the direction of PVEs in cardiac imaging change over time. This affects the accuracy of activity distributions estimates obtained during dynamic studies. The defect regions have different PVEs as compared to the normal myocardium. Cardiac motion contributes around 10% to the PVEs. PVC effectively removed both spill-in and spill-out in cardiac imaging. CONCLUSIONS: PVC improved left ventricular wall uniformity and quantitative accuracy. The best strategy for PVC was to compensate for the PVEs in each cardiac phase independently and treat severe uptake defects as independent regions from the normal myocardium.

A method for energy window optimization for quantitative tasks that includes the effects of model-mismatch on bias: application to Y-90 bremsstrahlung SPECT imaging.

Quantitative Yttrium-90 ((90)Y) bremsstrahlung single photon emission computed tomography (SPECT) imaging has shown great potential to provide reliable estimates of (90)Y activity distribution for targeted radionuclide therapy dosimetry applications. One factor that potentially affects the reliability of the activity estimates is the choice of the acquisition energy window. In contrast to imaging conventional gamma photon emitters where the acquisition energy windows are usually placed around photopeaks, there has been great variation in the choice of the acquisition energy window for (90)Y imaging due to the continuous and broad energy distribution of the bremsstrahlung photons. In quantitative imaging of conventional gamma photon emitters, previous methods for optimizing the acquisition energy window assumed unbiased estimators and used the variance in the estimates as a figure of merit (FOM). However, for situations, such as (90)Y imaging, where there are errors in the modeling of the image formation process used in the reconstruction there will be bias in the activity estimates. In (90)Y bremsstrahlung imaging this will be especially important due to the high levels of scatter, multiple scatter, and collimator septal penetration and scatter. Thus variance will not be a complete measure of reliability of the estimates and thus is not a complete FOM. To address this, we first aimed to develop a new method to optimize the energy window that accounts for both the bias due to model-mismatch and the variance of the activity estimates. We applied this method to optimize the acquisition energy window for quantitative (90)Y bremsstrahlung SPECT imaging in microsphere brachytherapy. Since absorbed dose is defined as the absorbed energy from the radiation per unit mass of tissues in this new method we proposed a mass-weighted root mean squared error of the volume of interest (VOI) activity estimates as the FOM. To calculate this FOM, two analytical expressions were derived for calculating the bias due to model-mismatch and the variance of the VOI activity estimates, respectively. To obtain the optimal acquisition energy window for general situations of interest in clinical (90)Y microsphere imaging, we generated phantoms with multiple tumors of various sizes and various tumor-to-normal activity concentration ratios using a digital phantom that realistically simulates human anatomy, simulated (90)Y microsphere imaging with a clinical SPECT system and typical imaging parameters using a previously validated Monte Carlo simulation code, and used a previously proposed method for modeling the image degrading effects in quantitative SPECT reconstruction. The obtained optimal acquisition energy window was 100-160 keV. The values of the proposed FOM were much larger than the FOM taking into account only the variance of the activity estimates, thus demonstrating in our experiment that the bias of the activity estimates due to model-mismatch was a more important factor than the variance in terms of limiting the reliability of activity estimates.

Development and evaluation of an improved quantitative (90)Y bremsstrahlung SPECT method.

PURPOSE: Yttrium-90 ((90)Y) is one of the most commonly used radionuclides in targeted radionuclide therapy (TRT). Since it decays with essentially no gamma photon emissions, surrogate radionuclides (e.g., (111)In) or imaging agents (e.g., (99m)Tc MAA) are typically used for treatment planning. It would, however, be useful to image (90)Y directly in order to confirm that the distributions measured with these other radionuclides or agents are the same as for the (90)Y labeled agents. As a result, there has been a great deal of interest in quantitative imaging of (90)Y bremsstrahlung photons using single photon emission computed tomography (SPECT) imaging. The continuous and broad energy distribution of bremsstrahlung photons, however, imposes substantial challenges on accurate quantification of the activity distribution. The aim of this work was to develop and evaluate an improved quantitative (90)Y bremsstrahlung SPECT reconstruction method appropriate for these imaging applications. METHODS: Accurate modeling of image degrading factors such as object attenuation and scatter and the collimator-detector response is essential to obtain quantitatively accurate images. All of the image degrading factors are energy dependent. Thus, the authors separated the modeling of the bremsstrahlung photons into multiple categories and energy ranges. To improve the accuracy, the authors used a bremsstrahlung energy spectrum previously estimated from experimental measurements and incorporated a model of the distance between (90)Y decay location and bremsstrahlung emission location into the SIMIND code used to generate the response functions and kernels used in the model. This improved Monte Carlo bremsstrahlung simulation was validated by comparison to experimentally measured projection data of a (90)Y line source. The authors validated the accuracy of the forward projection model for photons in the various categories and energy ranges using the validated Monte Carlo (MC) simulation method. The forward projection model was incorporated into an iterative ordered subsets-expectation maximization (OS-EM) reconstruction code to allow for quantitative SPECT reconstruction. The resulting code was validated using both a physical phantom experiment with spherical objects in a warm background and a realistic anatomical phantom simulation. In the physical phantom study, the authors evaluated the method in terms of quantitative accuracy of activity estimates in the spheres; in the simulation study, the authors evaluated the accuracy and precision of activity estimates from various organs and compared them to results from a previously proposed method. RESULTS: The authors demonstrated excellent agreement between the experimental measurement and Monte Carlo simulation. In the XCAT phantom simulation, the proposed method achieved much better accuracy in the modeling (error in photon counts was -1.1 %) compared to a previously proposed method (errors were more than 20 %); the quantitative accuracy of activity estimates was excellent for all organs (errors were from -1.6 % to 11.9 %) and comparable to previously published results for (131)I using the same collimator. CONCLUSIONS: The proposed (90)Y bremsstrahlung SPECT reconstruction method provided very accurate estimates of organ activities, with accuracies approaching those previously observed for (131)I. The method may be useful in verifying organ doses for targeted radionuclide therapy using (90)Y.

Development and evaluation of a model-based downscatter compensation method for quantitative I-131 SPECT.

PURPOSE: The radionuclide 131I has found widespread use in targeted radionuclide therapy (TRT), partly due to the fact that it emits photons that can be imaged to perform treatment planning or posttherapy dose verification as well as beta rays that are suitable for therapy. In both the treatment planning and dose verification applications, it is necessary to estimate the activity distribution in organs or tumors at several time points. In vivo estimates of the 131I activity distribution at each time point can be obtained from quantitative single-photon emission computed tomography (QSPECT) images and organ activity estimates can be obtained either from QSPECT images or quantification of planar projection data. However, in addition to the photon used for imaging, 131I decay results in emission of a number of other higher-energy photons with significant abundances. These higher-energy photons can scatter in the body, collimator, or detector and be counted in the 364 keV photopeak energy window, resulting in reduced image contrast and degraded quantitative accuracy; these photons are referred to as downscatter. The goal of this study was to develop and evaluate a model-based downscatter compensation method specifically designed for the compensation of high-energy photons emitted by 131I and detected in the imaging energy window. METHODS: In the evaluation study, we used a Monte Carlo simulation (MCS) code that had previously been validated for other radionuclides. Thus, in preparation for the evaluation study, we first validated the code for 131I imaging simulation by comparison with experimental data. Next, we assessed the accuracy of the downscatter model by comparing downscatter estimates with MCS results. Finally, we combined the downscatter model with iterative reconstruction-based compensation for attenuation (A) and scatter (S) and the full (D) collimator-detector response of the 364 keV photons to form a comprehensive compensation method. We evaluated this combined method in terms of quantitative accuracy using the realistic 3D NCAT phantom and an activity distribution obtained from patient studies. We compared the accuracy of organ activity estimates in images reconstructed with and without addition of downscatter compensation from projections with and without downscatter contamination. RESULTS: We observed that the proposed method provided substantial improvements in accuracy compared to no downscatter compensation and had accuracies comparable to reconstructions from projections without downscatter contamination. CONCLUSIONS: The results demonstrate that the proposed model-based downscatter compensation method is effective and may have a role in quantitative 131I imaging.

Effects of shortened acquisition time on accuracy and precision of quantitative estimates of organ activity.

PURPOSE: Quantitative estimation of in vivo organ uptake is an essential part of treatment planning for targeted radionuclide therapy. This usually involves the use of planar or SPECT scans with acquisition times chosen based more on image quality considerations rather than the minimum needed for precise quantification. In previous simulation studies at clinical count levels (185 MBq 111In), the authors observed larger variations in accuracy of organ activity estimates resulting from anatomical and uptake differences than statistical noise. This suggests that it is possible to reduce the acquisition time without substantially increasing the variation in accuracy. METHODS: To test this hypothesis, the authors compared the accuracy and variation in accuracy of organ activity estimates obtained from planar and SPECT scans at various count levels. A simulated phantom population with realistic variations in anatomy and biodistribution was used to model variability in a patient population. Planar and SPECT projections were simulated using previously validated Monte Carlo simulation tools. The authors simulated the projections at count levels approximately corresponding to 1.5-30 min of total acquisition time. The projections were processed using previously described quantitative SPECT (QSPECT) and planar (QPlanar) methods. The QSPECT method was based on the OS-EM algorithm with compensations for attenuation, scatter, and collimator-detector response. The QPlanar method is based on the ML-EM algorithm using the same model-based compensation for all the image degrading effects as the QSPECT method. The volumes of interests (VOIs) were defined based on the true organ configuration in the phantoms. The errors in organ activity estimates from different count levels and processing methods were compared in terms of mean and standard deviation over the simulated phantom population. RESULTS: There was little degradation in quantitative reliability when the acquisition time was reduced by half for the QSPECT method (the mean error changed by < 1%, e.g., 0.9%-0.3% = 0.6% for the spleen). The magnitude of the errors and variations in errors for large organ with high uptake were still acceptable for 1.5 min scans, even though the errors were slightly larger than those for the 30 min scans (i.e., < 2% for liver, < 3% for heart). The errors over the ranges of scan times studied for the QPlanar method were all within 0.3% for all organs. CONCLUSIONS: These data indicate that, for the purposes of organ activity estimation, acquisition times could be reduced at least by a factor of 2 for the QSPECT and QPlanar methods with little effect on the errors in organ activity estimates. The acquisition time can be further reduced for the QPlanar method, assuming well-registered VOIs are available and the activity distribution in organs can be treated as uniform. Although the differences in accuracy and precision were statistically significant for all the acquisition times shorter than 30 min, the magnitude of the changes in accuracy and precision were small and likely not clinically important. The reduction in SPECT acquisition time justified by this study makes the use of SPECT a more clinically practical alternative to conventional planar scanning for targeted radiotherapy treatment planning.

Arterial wall dosimetry for non-Hodgkin lymphoma patients treated with radioimmunotherapy.

UNLABELLED: Tumors in non-Hodgkin lymphoma (NHL) patients are often proximal to the major blood vessels in the abdomen or neck. In external-beam radiotherapy, these tumors present a challenge because imaging resolution prevents the beam from being targeted to the tumor lesion without also irradiating the artery wall. This problem has led to potentially life-threatening delayed toxicity. Because radioimmunotherapy has resulted in long-term survival of NHL patients, we investigated whether the absorbed dose (AD) to the artery wall in radioimmunotherapy of NHL is of potential concern for delayed toxicity. SPECT resolution is not sufficient to enable dosimetric analysis of anatomic features of the thickness of the aortic wall. Therefore, we present a model of aortic wall toxicity based on data from 4 patients treated with (131)I-tositumomab. METHODS: Four NHL patients with periaortic tumors were administered pretherapeutic (131)I-tositumomab. Abdominal SPECT and whole-body planar images were obtained at 48, 72, and 144 h after tracer administration. Blood-pool activity concentrations were obtained from regions of interest drawn on the heart on the planar images. Tumor and blood activity concentrations, scaled to therapeutic administered activities-both standard and myeloablative-were input into a geometry and tracking model (GEANT, version 4) of the aorta. The simulated energy deposited in the arterial walls was collected and fitted, and the AD and biologic effective dose values to the aortic wall and tumors were obtained for standard therapeutic and hypothetical myeloablative administered activities. RESULTS: Arterial wall ADs from standard therapy were lower (0.6-3.7 Gy) than those typical from external-beam therapy, as were the tumor ADs (1.4-10.5 Gy). The ratios of tumor AD to arterial wall AD were greater for radioimmunotherapy by a factor of 1.9-4.0. For myeloablative therapy, artery wall ADs were in general less than those typical for external-beam therapy (9.4-11.4 Gy for 3 of 4 patients) but comparable for 1 patient (32.6 Gy). CONCLUSION: Blood vessel radiation dose can be estimated using the software package 3D-RD combined with GEANT modeling. The dosimetry analysis suggested that arterial wall toxicity is highly unlikely in standard dose radioimmunotherapy but should be considered a potential concern and limiting factor in myeloablative therapy.

Development and validation of a Monte Carlo simulation tool for multi-pinhole SPECT.

PURPOSE: In this work, we developed and validated a Monte Carlo simulation (MCS) tool for investigation and evaluation of multi-pinhole (MPH) SPECT imaging. PROCEDURES: This tool was based on a combination of the SimSET and MCNP codes. Photon attenuation and scatter in the object, as well as penetration and scatter through the collimator detector, are modeled in this tool. It allows accurate and efficient simulation of MPH SPECT with focused pinhole apertures and user-specified photon energy, aperture material, and imaging geometry. The MCS method was validated by comparing the point response function (PRF), detection efficiency (DE), and image profiles obtained from point sources and phantom experiments. A prototype single-pinhole collimator and focused four- and five-pinhole collimators fitted on a small animal imager were used for the experimental validations. We have also compared computational speed among various simulation tools for MPH SPECT, including SimSET-MCNP, MCNP, SimSET-GATE, and GATE for simulating projections of a hot sphere phantom. RESULTS: We found good agreement between the MCS and experimental results for PRF, DE, and image profiles, indicating the validity of the simulation method. The relative computational speeds for SimSET-MCNP, MCNP, SimSET-GATE, and GATE are 1: 2.73: 3.54: 7.34, respectively, for 120-view simulations. We also demonstrated the application of this MCS tool in small animal imaging by generating a set of low-noise MPH projection data of a 3D digital mouse whole body phantom. CONCLUSIONS: The new method is useful for studying MPH collimator designs, data acquisition protocols, image reconstructions, and compensation techniques. It also has great potential to be applied for modeling the collimator-detector response with penetration and scatter effects for MPH in the quantitative reconstruction method.

Evaluation of quantitative imaging methods for organ activity and residence time estimation using a population of phantoms having realistic variations in anatomy and uptake.

Estimating organ residence times is an essential part of patient-specific dosimetry for radioimmunotherapy (RIT). Quantitative imaging methods for RIT are often evaluated using a single physical or simulated phantom but are intended to be applied clinically where there is variability in patient anatomy, biodistribution, and biokinetics. To provide a more relevant evaluation, the authors have thus developed a population of phantoms with realistic variations in these factors and applied it to the evaluation of quantitative imaging methods both to find the best method and to demonstrate the effects of these variations. Using whole body scans and SPECT/CT images, organ shapes and time-activity curves of 111In ibritumomab tiuxetan were measured in dosimetrically important organs in seven patients undergoing a high dose therapy regimen. Based on these measurements, we created a 3D NURBS-based cardiac-torso (NCAT)-based phantom population. SPECT and planar data at realistic count levels were then simulated using previously validated Monte Carlo simulation tools. The projections from the population were used to evaluate the accuracy and variation in accuracy of residence time estimation methods that used a time series of SPECT and planar scans, Quantitative SPECT (QSPECT) reconstruction methods were used that compensated for attenuation, scatter, and the collimator-detector response. Planar images were processed with a conventional (CPlanar) method that used geometric mean attenuation and triple-energy window scatter compensation and a quantitative planar (QPlanar) processing method that used model-based compensation for image degrading effects. Residence times were estimated from activity estimates made at each of five time points. The authors also evaluated hybrid methods that used CPlanar or QPlanar time-activity curves rescaled to the activity estimated from a single QSPECT image. The methods were evaluated in terms of mean relative error and standard deviation of the relative error in the residence time estimates taken over the phantom population. The mean errors in the residence time estimates over all the organs were < 9.9% (pure QSPECT), < 13.2% (pure QPLanar), < 7.2% (hybrid QPlanar/QSPECT), < 19.2% (hybrid CPlanar/QSPECT), and 7%-159% (pure CPlanar). The standard deviations of the errors for all the organs over all the phantoms were < 9.9%, < 11.9%, < 10.8%, < 22.0%, and < 107.9% for the same methods, respectively. The processing methods differed both in terms of their average accuracy and the variation of the accuracy over the population of phantoms, thus demonstrating the importance of using a phantom population in evaluating quantitative imaging methods. Hybrid CPlanar/QSPECT provided improved accuracy compared to pure CPlanar and required the addition of only a single SPECT acquisition. The QPlanar or hybrid QPlanar/QSPECT methods had mean errors and standard deviations of errors that approached those of pure QSPECT while providing simplified image acquisition protocols, and thus may be more clinically practical.

Application of three-class ROC analysis to task-based image quality assessment of simultaneous dual-isotope myocardial perfusion SPECT (MPS).

The diagnosis of cardiac disease using dual-isotope myocardial perfusion SPECT (MPS) is based on the defect status in both stress and rest images, and can be modeled as a three-class task of classifying patients as having no, reversible, or fixed perfusion defects. Simultaneous acquisition protocols for dual-isotope MPS imaging have gained much interest due to their advantages including perfect registration of the (201)Tl and (99m)Tc images in space and time, increased patient comfort, and higher clinical throughput. As a result of simultaneous acquisition, however, crosstalk contamination, where photons emitted by one isotope contribute to the image of the other isotope, degrades image quality. Minimizing the crosstalk is important in obtaining the best possible image quality. One way to minimize the crosstalk is to optimize the injected activity of the two isotopes by considering the three-class nature of the diagnostic problem. To effectively do so, we have previously developed a three-class receiver operating characteristic (ROC) analysis methodology that extends and unifies the decision theoretic, linear discriminant analysis, and psychophysical foundations of binary ROC analysis in a three-class paradigm. In this work, we applied the proposed three-class ROC methodology to the assessment of the image quality of simultaneous dual-isotope MPS imaging techniques and the determination of the optimal injected activity combination. In addition to this application, the rapid development of diagnostic imaging techniques has produced an increasing number of clinical diagnostic tasks that involve not only disease detection, but also disease characterization and are thus multiclass tasks. This paper provides a practical example of the application of the proposed three-class ROC analysis methodology to medical problems.

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.