Rapid dual-injection single-scan 13N-ammonia PET for quantification of rest and stress myocardial blood flows.

Quantification of myocardial blood flows at rest and stress using 13N-ammonia PET is an established method; however, current techniques require a waiting period of about 1 h between scans. The objective of this study was to test a rapid dual-injection single-scan approach, where 13N-ammonia injections are administered 10 min apart during rest and adenosine stress. Dynamic PET data were acquired in six human subjects using imaging protocols that provided separate single-injection scans as gold standards. Rest and stress data were combined to emulate rapid dual-injection data so that the underlying activity from each injection was known exactly. Regional blood flow estimates were computed from the dual-injection data using two methods: background subtraction and combined modelling. The rapid dual-injection approach provided blood flow estimates very similar to the conventional single-injection standards. Rest blood flow estimates were affected very little by the dual-injection approach, and stress estimates correlated strongly with separate single-injection values (r=0.998, mean absolute difference=0.06 ml min-1 g-1). An actual rapid dual-injection scan was successfully acquired in one subject and further demonstrates feasibility of the method. This study with a limited dataset demonstrates that blood flow quantification can be obtained in only 20 min by the rapid dual-injection approach with accuracy similar to that of conventional separate rest and stress scans. The rapid dual-injection approach merits further development and additional evaluation for potential clinical use.

Rapid dual-tracer PTSM+ATSM PET imaging of tumour blood flow and hypoxia: a simulation study.

Blood flow and hypoxia are interrelated aspects of physiology that affect cancer treatment and response. Cu-PTSM and Cu-ATSM are related PET tracers for blood flow and hypoxia, and the ability to rapidly image both tracers in a single scan would bring several advantages over conventional single-tracer techniques. Using dynamic imaging with staggered injections, overlapping signals for multiple PET tracers may be recovered utilizing information from kinetics and radioactive decay. In this work, rapid dual-tracer PTSM+ATSM PET was simulated and tested as a function of injection delay, order and relative dose for several copper isotopes, and the results were compared relative to separate single-tracer data. Time-activity curves representing a broad range of tumour blood flow and hypoxia levels were simulated, and parallel dual-tracer compartment modelling was used to recover the signals for each tracer. The main results were tested further using a torso phantom simulation of PET tumour imaging. Using scans as short as 30 minutes, the dual-tracer method provided measures of blood flow and hypoxia similar to single-tracer imaging. The best performance was obtained by injecting PTSM first and using a somewhat higher dose for ATSM. Comparable results for different copper isotopes suggest that tracer kinetics with staggered injections play a more important role than radioactive decay in the signal separation process. Rapid PTSM+ATSM PET has excellent potential for characterizing both tumour blood flow and hypoxia in a single, fast scan, provided that technological hurdles related to algorithm development and routine use can be overcome.

Survey of parallel slat collimator designs for hybrid PET imaging.

Hybrid PET gamma cameras with coincidence detection electronics are commonly equipped with parallel slat collimators in order to reduce detection of singles and scattered photons, and create a pseudo-2D imaging geometry. The objective of this work was to survey a broad range of parallel slat collimator designs using a series of Monte Carlo simulated PET acquisitions. Collimator properties including septal height, septal thickness and pitch were independently examined over a wide range of values. Simulations were performed for hybrid PET imaging of a long cylindrical phantom uniformly filled with water and radioactivity. The performance for each collimator design was evaluated in terms of the trues-to-singles ratio, scatter fraction, and noise equivalent count rate for a wide range of camera trigger rates. Results indicate that increasing septal height offers the biggest performance gain. Septal thickness should be at least 0.5 mm, and should be optimized in conjunction with pitch to obtain the best performance. This survey provides the groundwork necessary for optimizing slat collimators, and provides a starting point for investigating new slat collimator designs.

4D maximum a posteriori reconstruction in dynamic SPECT using a compartmental model-based prior.

A 4D ordered-subsets maximum a posteriori (OSMAP) algorithm for dynamic SPECT is described which uses a temporal prior that constrains each voxel's behaviour in time to conform to a compartmental model. No a priori limitations on kinetic parameters are applied; rather, the parameter estimates evolve as the algorithm iterates to a solution. The estimated parameters and time-activity curves are used within the reconstruction algorithm to model changes in the activity distribution as the camera rotates, avoiding artefacts due to inconsistencies of data between projection views. This potentially allows for fewer, longer-duration scans to be used and may have implications for noise reduction. The algorithm was evaluated qualitatively using dynamic 99mTc-teboroxime SPECT scans in two patients, and quantitatively using a series of simulated phantom experiments. The OSMAP algorithm resulted in images with better myocardial uniformity and definition, gave time-activity curves with reduced noise variations, and provided wash-in parameter estimates with better accuracy and lower statistical uncertainty than those obtained from conventional ordered-subsets expectation-maximization (OSEM) processing followed by compartmental modelling. The new algorithm effectively removed the bias in k21 estimates due to inconsistent projections for sampling schedules as slow as 60 s per timeframe, but no improvement in wash-out parameter estimates was observed in this work. The proposed dynamic OSMAP algorithm provides a flexible framework which may benefit a variety of dynamic tomographic imaging applications.

Feasibility of dual-isotope coincidence/single-photon imaging of the myocardium.

UNLABELLED: Hybrid PET scanners offer the possibility of obtaining myocardial viability information from coincidence imaging of the positron emitter (18)F-FDG and perfusion measurements from a single-photon tracer-potentially simultaneously. This new approach is less costly and more readily available than dedicated PET and offers potential for improved FDG resolution and sensitivity compared with SPECT with 511-keV collimators. Simultaneous imaging of the coincidence and single-photon events offers the further advantages of automatic image registration and reduced imaging time. However, the feasibility of simultaneous coincidence/single-photon imaging or even immediately sequential imaging is unknown. In this study, the potential of using standard low-energy high-resolution (LEHR) collimators with hybrid PET to obtain coincidence and SPECT data was assessed. METHODS: Phantom and human studies were performed to investigate the effect of LEHR collimators on FDG coincidence imaging with a hybrid PET system, the effect of the presence of (99m)Tc during FDG coincidence imaging with LEHR collimators, and the effect of the presence of FDG during (99m)Tc SPECT imaging. RESULTS: FDG images were somewhat degraded (a measure of myocardial nonuniformity increased 10%) with LEHR collimators. With 148 MBq (4 mCi) (99m)Tc present during FDG imaging of a phantom, image quality was maintained and the number of detected coincidences changed by <5%. With (99m)Tc/(18)F whole-body ratios of 7:1, crosstalk from (18)F photons accounted for the majority of counts in the (99m)Tc SPECT images and resulted in severe artifacts. The artifacts were decreased with a simple crosstalk correction scheme but remained problematic. CONCLUSION: (99m)Tc/(18)F ratios of at least 9:1 and state-of-the-art reconstruction and crosstalk correction are likely to be required to perform immediately sequential coincidence/single-photon imaging of the myocardium with clinically useful results. Additional challenges remain before simultaneous imaging of coincidence events and single photons can be realized in practice.

Compartmental modeling of technetium-99m-labeled teboroxime with dynamic single-photon emission computed tomography: comparison with static thallium-201 in a canine model.

UNLABELLED: Di Bella EVR, Ross SG, Kadrmas DJ, et al. Compartmental modeling of technetium-99m-labeled teboroxime with dynamic single-photon emission computed tomography: Comparison with static thallium-201 in a canine model. Invest Radiol 2001;36:178-185. RATIONALE AND OBJECTIVES: A compartmental modeling approach to deriving kinetic parameters from a time series of single-photon emission computed tomography (SPECT) images of technetium-99m-labeled (99mTc-) teboroxime may have value for semiquantitative assessment of myocardial perfusion. This study investigated the value of the kinetic parameters derived from a two-compartment model of 99mTc-teboroxime for measuring myocardial perfusion and compared it with static thallium-201 (201Tl) uptake and microsphere-measured blood flow in dogs. METHODS: Experiments were successfully conducted in 9 of 11 open-chest dogs. During adenosine stress, a single complete set of projections of 201Tl uptake was acquired. 99mTc-teboroxime was then injected during adenosine stress, and a complete set of projections was acquired every 5.7 seconds for 17 minutes. Resting studies were performed on 4 of the animals. All of the projection sets were reconstructed with an iterative algorithm and incorporated corrections for attenuation and the geometric response of the collimators. Regional kinetic parameters (washin and washout) were determined semiautomatically from the time series of reconstructed 99mTc-teboroxime images and registered with microsphere data. Regional washin estimates were compared with 201Tl intensities and myocardial blood flows determined from microspheres. RESULTS: Optimally scaled 99mTc-teboroxime washin parameters and 201Tl uptakes were correlated with microsphere-determined blood flows (r = 0.91, y = 0. 99x + 0.01, and r = 0.92, y = 0.88x + 0.28, respectively). In six of the studies, the left anterior descending coronary artery was occluded, and stress occluded-to-normal (O/N) ratios were calculated. The O/N ratios were 0.32 +/- 0.17 as determined from microspheres injected with 201Tl and 0.38 +/- 0.29 from microspheres injected with 99mTc-teboroxime (P = NS). The O/N ratios were 0.48 +/- 0.16 for static 201Tl uptake and 0.27 +/- 0.21 for 99mTc-teboroxime washin (P < 0.05). CONCLUSIONS: Both 201Tl uptake and 99mTc-teboroxime kinetic parameters were well correlated with flow. The 99mTc-teboroxime washin parameters offer semiquantitative flow values and provide greater defect contrast than can be obtained with 201Tl uptake values.

Static Versus Dynamic Teboroxime Myocardial Perfusion SPECT in Canines.

Tc-99m-teboroxime is a perfusion tracer with high myocardial extraction, fast washin and washout kinetics, and excellent imaging properties. The fast kinetics pose some problems for static imaging, but they also allow for back-to-back stress / rest studies to be performed very quickly. Furthermore, such fast kinetics are ideally suited for dynamic imaging. We have compared static versus dynamic myocardial perfusion SPECT with teboroxime in canines using microsphere-derived flow values as the gold standard. Dynamic data were successfully acquired at rest and under adenosine stress in seven dogs using a fast serial scanning protocol. The data were analyzed in two ways: summing timeframes to create a single, static dataset with consistent projections; and 4D reconstruction and kinetic parameter estimation for a two compartment model. In both cases imaging data (voxel intensity or washin rate parameter) were correlated with flow values measured by microspheres. The static summing procedure that produced the best correlation with flow consisted of summing the projection data acquired from 60 to 180 seconds post-injection. The washin rate parameter was found to provide better correlation with flow than static image intensity in six of seven animals. When the data were pooled over all studies, washin provided significantly better correlation with flow than static imaging (p<0.01). We conclude that dynamic imaging of teboroxime with compartmental modeling provides a better measure of flow than can be obtained from static imaging techniques.

SPECT Imaging of Teboroxime during Myocardial Blood Flow Changes.

Kinetic parameters and static images from dynamic SPECT imaging of (99m)Tc-teboroxime have been shown to reflect blood flow in dogs and in humans at rest and during adenosine stress. When compartment modeling is used, steady-state physiological conditions are assumed. With standard adenosine stress protocols, imaging of teboroxime would likely involve significant changes in flow, even if performed only for five minutes. These flow changes may significantly bias the kinetic parameter estimates. On the other hand, when static imaging is performed, large flow changes during acquisition may improve contrast between normal and occluded regions. Computer simulations were performed to determine the effect of changing flows on kinetic parameter estimation and on static (average tissue uptake) images. Two canine studies were also performed in which adenosine was given with a standard protocol, and then imaging was repeated with adenosine infusion held constant. The simulations predicted biases on the order of 7% for kinetic washin parameter estimation and 18% for the washout parameter. Contrast for static studies was found to depend critically on the time-activity behavior of the distribution as well as on the stress protocol. The differences in washin contrast from the standard and continous adenosine dog studies was slightly larger than predicted from the simulations. Optimal imaging of teboroxime with adenosine using compartment modeling will require non-standard adenosine stress protocols, although sub-optimal imaging may still be useful clinically.

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.

Simultaneous technetium-99m/thallium-201 SPECT imaging with model-based compensation for cross-contaminating effects.

Simultaneous acquisition of dual-isotope SPECT data offers a number of advantages over separately acquired data; however, simultaneous acquisition can result in cross-contamination between isotopes. In this work we propose and evaluate two frameworks for iterative model-based compensation of cross-contamination in dual-isotope SPECT. The methods were applied to cardiac imaging with technetium-99m-sestamibi and thallium-201, and they were compared with a subtraction-based compensation method using a cross-talk estimate obtained from an auxiliary energy window. Monte Carlo simulations were performed to carefully study aspects of bias and noise for the methods, and a torso phantom with cardiac insert was used to evaluate the performance of the methods for experimentally acquired data. The cross-talk compensation methods substantially improved lesion contrast and significantly reduced quantitative errors for simultaneously acquired data. Thallium image normalized mean square error (NMSE) was reduced from 0.522 without cross-talk compensation to as low as 0.052 with model-based cross-talk compensation. This is compared with a NMSE of 0.091 for the subtraction-based compensation method. The application of a preliminary model for cross-talk arising from lead fluorescence x-rays and collimator scatter gave promising results, and the future development of a more accurate model for collimator interactions would probably benefit simultaneous Tc/Tl imaging. Model-based compensation methods provide feasible cross-talk compensation in clinically acceptable times, and they may ultimately make simultaneous dual-isotope protocols an effective alternative for many imaging procedures.

Application of reconstruction-based scatter compensation to thallium-201 SPECT: implementations for reduced reconstructed image noise.

Scatter compensation in Tl-201 single photon emission computed tomography (SPECT) presents an interesting challenge because of the multiple emission energies and relatively large proportion of scattered photons. In this paper, we present a simulation study investigating reconstructed image noise levels arising from various implementations of iterative reconstruction-based scatter compensation (RBSC) in Tl-201 SPECT. A two-stage analysis was used to study single and multiple energy window implementations of reconstruction-based scatter compensation, and RBSC was compared to the upper limits on performance for other approaches to handling scatter. In the first stage, singular value decomposition of the system transfer matrix was used to analyze noise levels in a manner independent of the choice of reconstruction algorithm, providing results valid across a wide range of regularizations. In the second stage, the data were reconstructed using maximum-likelihood expectation-maximization, and the noise properties of the resultant images were analyzed. The best RBSC performance was obtained using multiple energy windows, one for each emission photopeak, and RBSC outperformed the upper limit on subtraction-based compensation methods. Implementing RBSC with the correct choice of energy window acquisition scheme is a promising method for performing scatter compensation for Tl-201 SPECT.

Fast implementations of reconstruction-based scatter compensation in fully 3D SPECT image reconstruction.

Accurate scatter compensation in SPECT can be performed by modelling the scatter response function during the reconstruction process. This method is called reconstruction-based scatter compensation (RBSC). It has been shown that RBSC has a number of advantages over other methods of compensating for scatter, but using RBSC for fully 3D compensation has resulted in prohibitively long reconstruction times. In this work we propose two new methods that can be used in conjunction with existing methods to achieve marked reductions in RBSC reconstruction times. The first method, coarse-grid scatter modelling, significantly accelerates the scatter model by exploiting the fact that scatter is dominated by low-frequency information. The second method, intermittent RBSC, further accelerates the reconstruction process by limiting the number of iterations during which scatter is modelled. The fast implementations were evaluated using a Monte Carlo simulated experiment of the 3D MCAT phantom with 99mTc tracer, and also using experimentally acquired data with 201Tl tracer. Results indicated that these fast methods can reconstruct, with fully 3D compensation, images very similar to those obtained using standard RBSC methods, and in reconstruction times that are an order of magnitude shorter. Using these methods, fully 3D iterative reconstruction with RBSC can be performed well within the realm of clinically realistic times (under 10 minutes for 64 x 64 x 24 image reconstruction).

Analysis of the reconstructibility and noise properties of scattered photons in 99mTc SPECT.

Since scattered photons carry degraded spatial information, scatter is typically considered a source of contamination in SPECT. However, with the advent of scatter modelling methods and reconstruction-based scatter compensation (RBSC), it may be possible to utilize scattered data in a productive manner. In this work we analyse the reconstructibility of scattered photon projection data and investigate the potential for using scattered photons to reduce the noise levels of SPECT images. We have simulated projection data for an elliptical phantom containing three cold rods in a uniform background of 99mTc activity. A variety of photopeak and scatter energy windows were formed, as well as corresponding RBSC transfer matrices. Each statistically weighted matrix was decomposed using SVD and analysed in terms of reconstructibility and noise properties. Results indicate that scattered photons contain sufficient information to reconstruct the source activity, but the scatter-only matrices are very poorly conditioned. We have also evaluated several methods of utilizing scattered events via RBSC, and compared them with other, idealized methods of handling scatter. It was found that scattered photons can be used productively when photopeak and non-photopeak data are separated through the use of multiple energy windows. The RBSC methods outperformed ideal scatter subtraction, but fell short of methods which assume perfect discrimination between scattered and primary events. The knowledge gained by this study may help guide future research and lead to better approaches to handling scatter in SPECT.

Truncation artifact reduction in transmission CT for improved SPECT attenuation compensation.

Transmission computed tomography (TCT) has been shown to be an accurate method of acquiring non-uniform attenuation maps for single-photon emission computed tomography (SPECT) attenuation compensation. One commonly encountered problem, especially for convergent beam geometries, is image truncation. We describe two methods for reducing associated truncation artifacts, with the goal of improving SPECT attenuation compensation without unduly increasing imaging or reconstruction times: (i) the two-scan method, which reduces the degree of truncation by combining two short-duration, patient-shifted scans, and (ii) a quantitative extrapolation method, which fills in truncated projections accounting for the correct amount of attenuating medium in the slice. The methods are evaluated by imaging two phantoms on a fan beam TCT system. Projection sets are truncated to various degrees with software, and reconstructed images are compared to both untruncated filtered backprojection and iterative reconstructions of truncated data. A fundamental analysis of SPECT attenuation factors is performed, and attenuation compensation of a cardiac insert is analysed. Results indicate the two-scan method can effectively reduce the degree of truncation in many cases, and the quantitative extrapolation method greatly improves SPECT attenuation compensation over using truncated maps.