A non-parametric bootstrap approach for analysing the statistical properties of SPECT and PET images

Knowledge of the statistical properties of reconstructed single photon emission computed tomography (SPECT) and positron emission tomography (PET) images would be helpful for optimizing acquisition and image processing protocols. We describe a non-parametric bootstrap approach to accurately estimate the statistical properties of SPECT or PET images whatever the noise properties in the projections and the reconstruction algorithm. Using analytical simulations and real PET data, this method is shown to accurately predict the statistical properties, including the variance and covariance, of reconstructed pixel values for both linear (filtered backprojection) and non-linear (ordered subset expectation maximization) reconstruction algorithms.     

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.     

Functional neuroimaging in epilepsy: FDG PET and ictal SPECT.

Epileptogenic zones can be localized by F-18 fluorodeoxyglucose positron emission tomography (FDG PET) and ictal single-photon emission computed tomography(SPECT). In medial temporal lobe epilepsy, the diagnostic sensitivity of FDG PET or ictal SPECT is excellent, however, the sensitivity of MRI is so high that the incremental sensitivity by FDG PET or ictal SPECT has yet to be proven. When MRI findings are ambiguous or normal, or discordant with those of ictal EEG, FDG PET and ictal SPECT are helpful for localization without the need for invasive ictal EEG. In neocortical epilepsy, the sensitivities of FDG PET or ictal SPECT are fair. However, because almost a half of the patients are normal on MRI, FDG PET and ictal SPECT are helpful for localization or at least for lateralization in these non-lesional epilepsies in order to guide the subdural insertion of electrodes. Interpretation of FDG PET has been recently advanced by voxel-based analysis and automatic volume of interest analysis based on a population template. Both analytical methods confirmed the performance of previous visual interpretation results. Ictal SPECT was analyzed using subtraction methods(coregistered to MRI) and voxel-based analysis. Rapidity of injection of tracers, HMPAO versus ECD, and repeated ictal SPECT, which remain the technical issues of ictal SPECT, are detailed.     

A dual modality approach to quantitative quality control in emission tomography

Routine quality control (QC) and optimization of image quality of reconstructed images in single photon emission computed tomography (SPECT) and positron emission tomography (PET) remains a relatively qualitative exercise. With the advent of combined SPECT/CT and PET/CT devices, and accurate post hoc co-registration algorithms, the potential exists to utilize high resolution structural information for QC evaluation in addition to their use for anatomical correlation in clinical studies. The aim of this work was to explore, in principle, the uses of x-ray CT data of QC phantoms used in SPECT and PET to develop more objective assessments of performance of the emission tomographic (ET) devices and reconstructed data. A CT reconstruction of a novel ET QC phantom was segmented into the various compartments it contained. Using software, the voxel values in the different compartments were then altered to correspond to the concentration of the radioactivity in the actual scan of the same phantom on the SPECT system. This produces a high resolution version of a 'perfect' ET scan. Image co-registration techniques were then used to spatially align the synthetic high resolution SPECT scan to the measured SPECT scan. Various parameters can then be objectively derived from the registered data, for example, image contrast, spatial resolution, spatial non-uniformity, etc. In this study, we have used this approach to estimate spatial resolution (full width at half maximum, FWHM) and recovered contrast in reconstructed images of a SPECT phantom. Two independent methods were used to measure spatial resolution, obtaining excellent agreement. In conclusion, the ability to produce high resolution synthetic phantoms in emission tomography QC affords an objective approach to assessing system performance and optimizing protocols which is readily automated and quantifiable.     

Rapid calculation of detectability in Bayesian single photon emission computed tomography

We consider the calculation of lesion detectability using a mathematical model observer, the channelized Hotelling observer (CHO), in a signal-known-exactly/background-known-exactly detection task for single photon emission computed tomography (SPECT). We focus on SPECT images reconstructed with Bayesian maximum a posteriori methods. While model observers are designed to replace time-consuming studies using human observers, the calculation of CHO detectability is usually accomplished using a large number of sample images, which is still time consuming. We develop theoretical expressions for a measure of detectability, the signal-to-noise-ratio (SNR) of a CHO observer, that can be very rapidly evaluated. Key to our expressions are approximations to the reconstructed image covariance. In these approximations, we use methods developed in the PET literature, but modify them to reflect the different nature of attenuation and distance-dependent blur in SPECT. We validate our expressions with Monte Carlo methods. We show that reasonably accurate estimates of the SNR can be obtained at a computational expense equivalent to approximately two projection operations, and that evaluating SNR for subsequent lesion locations requires negligible additional computation.     

SPECT neuroimaging in schizophrenia with religious delusions.

Functional neuroimaging techniques such as single-positron emission computed tomography (SPECT) and positron emission tomography (PET) offer considerable scope for investigating disturbances of brain activity in psychiatric disorders. However, the heterogeneous nature of disorders such as schizophrenia limits the value of studies that group patients under this global label. Some have addressed this problem by considering schizophrenia at a syndromal level, but so far, few have focussed at the level of individual symptoms. We describe the first neuroimaging study of the specific symptom of religious delusions in schizophrenia. 99mTc HMPAO high-resolution SPECT neuroimaging showed an association of religious delusions with left temporal overactivation and reduced occipital uptake, particularly on the left.     

A comparison of MR-based attenuation correction in PET versus SPECT

Attenuation correction (AC) is a critical step in the reconstruction of quantitatively accurate positron emission tomography (PET) and single photon emission computed tomography (SPECT) images. Several groups have proposed magnetic resonance (MR)-based AC algorithms for application in hybrid PET/MR systems. However, none of these approaches have been tested on SPECT data. Since SPECT/MR systems are under active development, it is important to ascertain whether MR-based AC algorithms validated for PET can be applied to SPECT. To investigate this issue, two imaging experiments were performed: one with an anthropomorphic chest phantom and one with two groups of canines. Both groups of canines were imaged from neck to abdomen, one with PET/CT and MR (n = 4) and the other with SPECT/CT and MR (n = 4), while the phantom was imaged with all modalities. The quality of the nuclear medicine reconstructions using MR-based attenuation maps was compared between PET and SPECT on global and local scales. In addition, the sensitivity of these reconstructions to variations in the attenuation map was ascertained. On both scales, it was found that the SPECT reconstructions were of higher fidelity than the PET reconstructions. Further, they were less sensitive to changes to the MR-based attenuation map. Thus, MR-based AC algorithms that have been designed for PET/MR can be expected to demonstrate improved performance when used for SPECT/MR.     

Cardioprotective Effect of Fimasartan,a New Angiotensin Receptor Blocker,in a Porcine Model of Acute Myocardial Infarction

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI.

Graphical Abstract

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Noise propagation for iterative penalized-likelihood image reconstruction based on Fisher information

Iterative reconstruction algorithms have been widely used in PET and SPECT emission tomography. Accurate modeling of photon noise propagation is crucial for quantitative tomography applications. Iteration-based noise propagation methods have been developed for only a few algorithms that have explicit multiplicative update equations. And there are discrepancies between the iteration-based methods and Fessler's fixed-point method because of improper approximations. In this paper, we present a unified theoretical prediction of noise propagation for any penalized expectation maximization (EM) algorithm where the EM approach incorporates a penalty term. The proposed method does not require an explicit update equation. The update equation is assumed to be implicitly defined by a differential equation of a surrogate function. We derive the expressions using the implicit function theorem, Taylor series and the chain rule from vector calculus. We also derive the fixed-point expressions when iterative algorithms converge and show the consistency between the proposed method and the fixed-point method. These expressions are solely defined in terms of the partial derivatives of the surrogate function and the Fisher information matrices. We also apply the theoretical noise predictions for iterative reconstruction algorithms in emission tomography. Finally, we validate the theoretical predictions for MAP-EM and OSEM algorithms using Monte Carlo simulations with Jaszczak-like and XCAT phantoms, respectively.     

Nuclear imaging of autoimmunity: Focus on IBD and RA

There is a need for methods to improve the diagnosis, patient staging and evaluation of therapeutic response in patients with autoimmune conditions to improve patient care. Inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) are two inflammatory diseases characterized by involvement of innate and adaptive immune components that change the metabolic state of their respective target tissues, thus providing an opportunity for molecular imaging probes to detect such changes. Optimally, such probes and the imaging methods employed would be non-invasive, robust and reproducible, give a quantitative result, report on the status of the affected tissue(s) and respond to the effects of a therapeutic molecule. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are nuclear imaging approaches that have the potential to satisfy such requirements. In this review, the work to date and the potential of PET and SPECT imaging probes in these two inflammatory conditions, IBD and RA, are discussed.     

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

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

Validation of GATE Monte Carlo simulations of the GE Advance/Discovery LS PET scanners

The recently developed GATE (GEANT4 application for tomographic emission) Monte Carlo package, designed to simulate positron emission tomography (PET) and single photon emission computed tomography (SPECT) scanners, provides the ability to model and account for the effects of photon noncollinearity, off-axis detector penetration, detector size and response, positron range, photon scatter, and patient motion on the resolution and quality of PET images. The objective of this study is to validate a model within GATE of the General Electric (GE) Advance/Discovery Light Speed (LS) PET scanner. Our three-dimensional PET simulation model of the scanner consists of 12 096 detectors grouped into blocks, which are grouped into modules as per the vendor's specifications. The GATE results are compared to experimental data obtained in accordance with the National Electrical Manufactures Association/Society of Nuclear Medicine (NEMA/SNM), NEMA NU 2-1994, and NEMA NU 2-2001 protocols. The respective phantoms are also accurately modeled thus allowing us to simulate the sensitivity, scatter fraction, count rate performance, and spatial resolution. In-house software was developed to produce and analyze sinograms from the simulated data. With our model of the GE Advance/Discovery LS PET scanner, the ratio of the sensitivities with sources radially offset 0 and 10 cm from the scanner's main axis are reproduced to within 1% of measurements. Similarly, the simulated scatter fraction for the NEMA NU 2-2001 phantom agrees to within less than 3% of measured values (the measured scatter fractions are 44.8% and 40.9 +/- 1.4% and the simulated scatter fraction is 43.5 +/- 0.3%). The simulated count rate curves were made to match the experimental curves by using deadtimes as fit parameters. This resulted in deadtime values of 625 and 332 ns at the Block and Coincidence levels, respectively. The experimental peak true count rate of 139.0 kcps and the peak activity concentration of 21.5 kBq/cc were matched by the simulated results to within 0.5% and 0.1% respectively. The simulated count rate curves also resulted in a peak NECR of 35.2 kcps at 10.8 kBq/cc compared to 37.6 kcps at 10.0 kBq/cc from averaged experimental values. The spatial resolution of the simulated scanner matched the experimental results to within 0.2 mm.     

The use of the fusion protein RGD-HSA-TIMP2 as a tumor targeting imaging probe for SPECT and PET

The human serum albumin tissue inhibitor of metalloproteinase 2 (HSA-TIMP2) is known to possess antitumor activity, which has been attributed to its ability to inhibit endothelial cell proliferation by binding to integrin receptors. In this study, a fusion protein, cyclic arginine-glycine-aspartate (RGD)-HSA-TIMP2, formed by conjugating HSA-TIMP2 with a RGD peptide, and its (123)I- and (68)Ga-labeled compounds, were synthesized and evaluated with in vivo tumor imaging using single photon emission computed tomography (SPECT) and positron emission tomography (PET). RGD-HSA-TIMP2 was synthesized by covalent bonding of the RGD peptide to the side chain amino groups of HSA-TIMP2 from a two-step reaction involving from activation with N-succinimidyl iodoacetate. This conjugation improved the anticancer effect of HSA-TIMP2 in cancer cells. The (123)I- and (68)Ga-labeled fusion proteins were prepared and subsequently injected into the tail veins of mice bearing human glioblastoma cancer U87MG xenografts for SPECT and PET imaging and biodistribution studies. Tumor uptake of radioligand was high in both the PET images and in the biodistribution studies at 3 h after injection. These studies demonstrated that the new fusion protein has potential not only as an anticancer agent but also as a radioligand for the diagnosis of tumors.     

功能成像及其在肺癌放疗中的应用研究

功能成像在现在的放疗计划设计中具有十分重要的作用,在放疗中如何利用肺通气和灌注信息更好的保护肺功能已经引起了越来越多的关注。本文概述了一些用来评价肺通气和灌注水平的技术,包括单光子发射计算机断层扫描(SPECT)、正电子发射计算机断层扫描(PET)、磁共振成像(MRI)及计算机断层显像(CT)。这些技术都可以应用到肺癌患者的放疗计划设计中,在给予肿瘤足够治疗剂量的同时更好的保护具有正常功能的肺组织。文中分别对各种评价技术的临床应用方法进行了介绍。这些技术都具有各自不同的特点,其中4D-CT的发展最具前景,因此文中特别概述了在4D-CT中利用变形图像配准产生三维通气图像的技术。各种肺功能成像在图像引导放疗中的临床应用也在文中进行了概述。在所有肺功能成像技术中,4-D CT操作简便,空间分辨率高,因此具有更加广泛的应用价值。     

Recent advances in investigations into brain function and its clinical application

Recent advances in investigations into brain function and its clinical application are described. The investigations were divided into three method groups consisting of the examinations of; 1) brain electric activity; 2) imaging techniques on activated brain tissue; and 3) collation of the metabolic information on the area of brain focused on. The first group included electroencephalogram(EEG), dipole tracing(DT) and magnetoencephalogram(MEG). The second one, single photon emission computed tomography(SPECT), positron emission tomography(PET) and functional magnetic resonance imaging(fMRI), and the third, magnetic resonance spectrometry(MRS). Here I overview these examinations and report some cases diagnosed with these technologies.     

A pseudo-Poisson noise model for simulation of positron emission tomographic projection data.

Although radioactive decay obeys Poisson statistics, because of the corrections that are applied to the projection data prior to reconstruction, the noise in positron emission tomography (PET) projections does not follow a Poisson distribution. Use of Poisson noise when simulating PET projections in order to test the performance of reconstruction and processing techniques is therefore not appropriate. The magnitude of PET projection noise was observed to be as much as 10 to 100 times greater than Poisson noise in some instances. A quadratic function was found to fit the relationship between noise power spectral density and total projection count. The coefficients of the quadratic function were determined for projections of different tracer distributions and types. Using these observations, a method of simulating PET projections was developed based on a pseudo-Poisson noise model. Projections simulated according to this method are good approximations to real projection data and take into account the characteristics of individual PET cameras and particular tracer distributions. Such simulated projections have been valuable in predicting the performance of reconstruction algorithms. This approach can also be applied to single photon emission tomography.     

Molecular imaging applications for immunology

The use of multimodality molecular imaging has recently facilitated the study of molecular and cellular events in living subjects in a noninvasive and repetitive manner to improve the diagnostic capability of traditional assays. The noninvasive imaging modalities utilized for both small animal and human imaging include positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), ultrasound, and computed tomography (CT). Techniques specific to small-animal imaging include bioluminescent imaging (BIm) and fluorescent imaging (FIm). Molecular imaging permits the study of events within cells, the examination of cell trafficking patterns that relate to inflammatory diseases and metastases, and the ability to rapidly screen new drug treatments for distribution and effectiveness. In this paper, we will review the current field of molecular imaging assays (especially those utilizing PET and BIm modalities) and examine how they might impact animal models and human disease in the field of clinical immunology.