A deep neural network for positioning and inter-crystal scatter identification in multiplexed PET detectors: a simulation study.

Objective.High-resolution positron emission tomography (PET) relies on the accurate positioning of annihilation photons impinging the crystal array. However, conventional positioning algorithms in light-sharing PET detectors are often limited due to edge effects and/or the absence of additional information for identifying and correcting scattering within the crystal array (known as inter-crystal scattering). This study explores the feasibility of deep neural network (DNN) techniques for more precise event positioning in finely segmented and highly multiplexed PET detectors with light-sharing.Approach.Initially, a Geant4 Application for Tomographic Emission (GATE) simulation was used to study the spatial and statistical properties of inter-crystal scatter (ICS) events in finely segmented LYSO PET detectors. Next, a DNN for crystal localisation was designed, trained and tested with light distributions of photoelectric (P) and Compton + photoelectric (CP) events simulated using optical GATE and an analytical method to speed up data generation. Using the statistical properties of ICS events, an energy-guided positioning algorithm was then built into the DNN. The positioning algorithm enables selection of the unique or first crystal of interaction in P and CP events, respectively. Performance of the DNN was compared with Anger logic using light distributions from simulated 511 keV point sources placed at different locations around a single PET detector module.Main results. The fraction of events forward and backward scattered in the LYSO detector was 0.54 and 0.46, respectively, whereas naïve application of the Klein-Nishina formulation predicts 70% forward scatter. Despite coarse photodetector data due to signal multiplexing, the DNN demonstrated a crystal classification accuracy of 90% for P events and 82% for CP events. For crystal positioning, the DNN outperformed Anger logic by at least 34% and 14% for P and CP events, respectively. Further improvement is somewhat constrained by the physics-specifically, the ratio of backward to forward scattering of gamma rays within the crystal array being close to 1. This prevents selecting the first crystal of interaction in CP events with a high degree of certainty.Significance.Light sharing and multiplexed PET detectors are common in high-resolution PET, yet their traditional positioning algorithms often underperform due to edge effects and/or the difficulty in correcting ICS events. Our study indicates that DNN-based event positioning has the potential to enhance 2D coincidence event positioning accuracy by nearly a factor of 3 compared to Anger logic. However, further improvements are difficult to foresee without additional information such as event timing.

Virtual cylindrical PET for efficient DOI image reconstruction with sub-millimetre resolution.

Objective.Image reconstruction in high resolution, narrow bore PET scanners with depth of interaction (DOI) capability presents a substantial computational challenge due to the very high sampling in detector and image space. The aim of this study is to evaluate the use of a virtual cylinder in reducing the number of lines of response (LOR) for DOI-based reconstruction in high resolution PET systems while maintaining uniform sub-millimetre spatial resolution.Approach.Virtual geometry was investigated using the awake animal mousePET as a high resolution test case. Using GEANT4 Application for Tomographic Emission (GATE), we simulated the physical scanner and three virtual cylinder implementations with detector size 0.74 mm, 0.47 mm and 0.36 mm (vPET1, vPET2 and vPET3, respectively). The virtual cylinder condenses physical LORs stemming from various crystal pairs and DOI combinations, and which intersect a single virtual detector pair, into a single virtual LOR. Quantitative comparisons of the point spread function (PSF) at various positions within the field of view (FOV) were compared for reconstructions based on the vPET implementations and the physical scanner. We also assessed the impact of the anisotropic PSFs by reconstructing images of a micro Derenzo phantom.Main results.All virtual cylinder implementations achieved LOR data compression of at least 50% for DOI PET reconstruction. PSF anisotropy in radial and tangential profiles was chiefly influenced by DOI resolution and only marginally by virtual detector size. Spatial degradation introduced by virtual cylinders was most prominent in the axial profile. All virtual cylinders achieved sub-millimetre volumetric resolution across the FOV when 6-bin DOI reconstructions (3.3 mm DOI resolution) were performed. Using vPET2 with 6 DOI bins yielded nearly identical reconstructions to the non-virtual case in the transaxial plane, with an LOR compression factor of 86%. Resolution modelling significantly reduced the effects of the asymmetric PSF arising from the non-cylindrical geometry of mousePET.Significance.Narrow bore and high resolution PET scanners require detectors with DOI capability, leading to computationally demanding reconstructions due to the large number of LORs. In this study, we show that DOI PET reconstruction with 50%-86% LOR compression is possible using virtual cylinders while maintaining sub-millimetre spatial resolution throughout the FOV. The methodology and analysis can be extended to other scanners with DOI capability intended for high resolution PET imaging.

The potential advantages and workflow challenges of long axial field of view PET/CT.

Recently developed Long (≥100 cm) axial field of view (AFOV) PET/CT scanners are capable of producing images with higher signal-to-noise ratio, or performing faster whole-body acquisitions, or scanning with lower radiation dose to the patient, compared with conventional PET/CT scanners. These benefits, which arise due to their substantially higher, by more than an order of magnitude, geometric efficiency, have been well described in the recent literature. The introduction of Long AFOV PET/CT technology into the clinic also has important implications for the design and workflow of PET/CT facilities and their effects on radiation exposure to staff and patients. Maximising the considerable benefits of this technology requires a thorough understanding of the relationships between these factors to optimise workflows while appropriately managing radiation exposure. This article reviews current knowledge on PET/CT facility design, workflows and their effects on radiation exposure, identifies gaps in the literature and discusses the challenges that need to be considered with the introduction of Long AFOV PET/CT into the clinic.

Performance evaluation of a PET insert for preclinical MRI in stand-alone PET and simultaneous PET-MRI modes.

BACKGROUND: This study aimed to evaluate the performance of a preclinical PET insert in three configurations: as a stand-alone unit outside the MRI bore, inside the bore of a cryogen-free 3T MRI and, finally, while performing simultaneous PET/MRI studies. METHODS: The PET insert consists of two rings of six detectors, each detector comprising 8 × 12 SiPMs reading out dual offset layers of pixelated LYSO crystals with a 1.4-mm pitch. The inner diameter is 60 mm, transaxial field of view (FoV) 40 mm and axial FoV 98 mm. Evaluation was based on NEMA NU 4-2008 guidelines with appropriate modifications. Spatial resolution and sensitivity were measured inside and outside the MR bore. Image quality, count rate and quantitative performance were measured in all three configurations. The effect of temperature stability on PET sensitivity during fast spin echo sequences was also evaluated. B0 field homogeneity and T1 and T2 relaxation times were measured using a water-filled phantom, with and without simultaneous PET operation. Finally, PET and MRI scans of a mouse injected with 10 MBq [18F]NaF and a mouse injected with 16 MBq [18F]FDG were performed in sequential and simultaneous modes. RESULTS: Peak absolute sensitivity was 10.15% with an energy window of 250-750 keV. Absolute sensitivity values outside and inside the MR bore with MR idle agreed to within 0.1%. Outside the MR bore, spatial resolution was 1.21/1.59 mm FWHM (radial/tangential) 5 mm from the centre of the FoV which compared well with 1.19/1.26 mm FWHM inside the MR bore. There were no substantial differences between all three scan configurations in terms of peak NEC rate (175 kcps at 17 MBq), scatter or random fractions. Uniformity and recovery coefficients were also consistent between scanning modes. B0 field homogeneity and T1 and T2 relaxation times were unaltered by the presence of the PET insert. No significant differences were observed between sequential and simultaneous scans of the animals. CONCLUSIONS: We conclude that the performance of the PET insert and MRI system is not significantly affected by the scanning mode.

PET-ABC: fully Bayesian likelihood-free inference for kinetic models.

Aims.We describe an intuitive, easy to use method called PET-ABC that enables full Bayesian statistical inference from single subject dynamic PET data. The performance of PET-ABC was compared with weighted non-linear least squares (WNLS) in terms of reliability of kinetic parameter estimation and statistical power for model selection.Methods.Dynamic PET data based on 1-tissue and 2-tissue compartmental models were simulated with 2 noise models and 3 noise levels. PET-ABC was used to evaluate the reliability of parameter estimates under each condition. It was also used to perform model selection for a simulated noisy dataset composed of a mixture of 1- and 2-tissue compartment kinetics. Finally, PET-ABC was used to analyze a non-steady state dynamic [11C] raclopride study performed on a fully conscious rat administered either 2 mg.kg-1amphetamine or saline 20 min after tracer injection.Results.PET-ABC yielded posterior point estimates for model parameters with smaller variance than WNLS, as well as probability density functions indicating confidence intervals for those estimates. It successfully identified the superiority of a 2-tissue compartment model to fit the simulated mixed model data. For the drug challenge study, the post observation probability of striatal displacement of the PET signal was 0.9 for amphetamine and approximately 0 for saline, indicating a high probability of amphetamine-induced endogenous dopamine release in the striatum. PET-ABC also demonstrated superior statistical power to WNLS (0.87 versus 0.09) for selecting the correct model in a simulated ligand displacement study.Conclusions.PET-ABC is a simple and intuitive method that provides complete Bayesian statistical analysis of single subject dynamic PET data, including the extent to which model parameter estimates and model choice are supported by the data. Software for PET-ABC is freely available as part of thePETabcpackagehttps://github.com/cgrazian/PETabc.

Quantitative PET in the 2020s: a roadmap.

Positron emission tomography (PET) plays an increasingly important role in research and clinical applications, catalysed by remarkable technical advances and a growing appreciation of the need for reliable, sensitive biomarkers of human function in health and disease. Over the last 30 years, a large amount of the physics and engineering effort in PET has been motivated by the dominant clinical application during that period, oncology. This has led to important developments such as PET/CT, whole-body PET, 3D PET, accelerated statistical image reconstruction, and time-of-flight PET. Despite impressive improvements in image quality as a result of these advances, the emphasis on static, semi-quantitative 'hot spot' imaging for oncologic applications has meant that the capability of PET to quantify biologically relevant parameters based on tracer kinetics has not been fully exploited. More recent advances, such as PET/MR and total-body PET, have opened up the ability to address a vast range of new research questions, from which a future expansion of applications and radiotracers appears highly likely. Many of these new applications and tracers will, at least initially, require quantitative analyses that more fully exploit the exquisite sensitivity of PET and the tracer principle on which it is based. It is also expected that they will require more sophisticated quantitative analysis methods than those that are currently available. At the same time, artificial intelligence is revolutionizing data analysis and impacting the relationship between the statistical quality of the acquired data and the information we can extract from the data. In this roadmap, leaders of the key sub-disciplines of the field identify the challenges and opportunities to be addressed over the next ten years that will enable PET to realise its full quantitative potential, initially in research laboratories and, ultimately, in clinical practice.

Performance evaluation of quantitative SPECT/CT using NEMA NU 2 PET methodology.

Although PET is routinely evaluated using NEMA NU2 as standard in the clinic, standard methodology for evaluating the performance of quantitative SPECT systems has not been established. In this study, the quantitative performance of the Symbia Intevo SPECT/CT was evaluated for two common isotopes (99mTc, 177Lu) and benchmarked against the performance of a PET/CT. A further aim was to demonstrate the utility of adapting NEMA NU2 PET measurements to SPECT. In addition, dead-time and resolution recovery were evaluated to provide more complete system evaluations. Spatial resolution of the SPECT system at 1 cm from the center in the transverse direction was 13.1 mm and 22.4 mm for 99mTc and 177Lu respectively, compared with 4.3 mm (18F) and 5.8 mm (68Ga) for PET. Sensitivity at the center of the FoV was 119 cps MBq-1 and 48 cps MBq-1 (99mTc, 177Lu) for SPECT and 9632 cps MBq-1 and 8216 cps MBq-1 (18F, 68Ga) for PET. Scatter fraction was 0.25 and 0.36 (99mTc, 77Lu) for SPECT and 0.32 and 0.29 (18F, 68Ga) for PET. Contrast recovery coefficient in the largest spheres was 0.79 and 0.65 (99mTc, 177Lu) for SPECT, 1.00 and 0.97 (18F, 68Ga) for PET and the background variability was 2.7%, 6.5% (99mTc, 177Lu), 1.5% and 1.6% (18F, 68Ga), respectively. Partial volume effect was evaluated using the NEMA IQ phantom with six sphere inserts (diameter: 37 mm, 28 mm, 22 mm, 17 mm, 13 mm and 10 mm). Full contrast recovery was reached with the 17 mm for 18F, while SPECT did not reach full recovery for any sphere. Count rate losses were 2% for 99mTc at 1 GBq and 11% for 177Lu at 8.5 GBq which are well below the typical activities for clinical applications. We concluded NEMA NU2 methodology can be easily adapted to SPECT/CT as a routine quality assurance procedure in the clinic.

Direct Estimation of Voxel-Wise Neurotransmitter Response Maps From Dynamic PET Data.

Computational methods, such as the linear parametric neurotransmitter PET (lp-ntPET) method, have been developed to characterize the transient changes in radiotracer kinetics in the target tissue during endogenous neurotransmitter release. In this paper, we describe and evaluate a parametric reconstruction algorithm that uses an expectation maximization framework, along with the lp-ntPET model, to estimate the endogenous neurotransmitter response to stimuli directly from the measured PET data. Computer simulations showed that the proposed direct reconstruction method offers improved accuracy and precision for the estimated timing parameters of the neurotransmitter response at the voxel level ( td=1±2 min, for activation onset bias and standard deviation) compared with conventional post reconstruction modeling ( td=4±7 min). In addition, we applied the proposed direct parameter estimation methodology to a [11C]raclopride displacement study of an awake rat and generated parametric maps illustrating the magnitude of ligand displacement from striatum. Although the estimated parametric maps of activation magnitude obtained from both direct and post reconstruction methodologies suffered from false positive activations, the proposed direct reconstruction framework offered more reliable parametric maps when the activation onset parameter was constrained.

Open-field PET: Simultaneous brain functional imaging and behavioural response measurements in freely moving small animals.

A comprehensive understanding of how the brain responds to a changing environment requires techniques capable of recording functional outputs at the whole-brain level in response to external stimuli. Positron emission tomography (PET) is an exquisitely sensitive technique for imaging brain function but the need for anaesthesia to avoid motion artefacts precludes concurrent behavioural response studies. Here, we report a technique that combines motion-compensated PET with a robotically-controlled animal enclosure to enable simultaneous brain imaging and behavioural recordings in unrestrained small animals. The technique was used to measure in vivo displacement of [11C]raclopride from dopamine D2 receptors (D2R) concurrently with changes in the behaviour of awake, freely moving rats following administration of unlabelled raclopride or amphetamine. The timing and magnitude of [11C]raclopride displacement from D2R were reliably estimated and, in the case of amphetamine, these changes coincided with a marked increase in stereotyped behaviours and hyper-locomotion. The technique, therefore, allows simultaneous measurement of changes in brain function and behavioural responses to external stimuli in conscious unrestrained animals, giving rise to important applications in behavioural neuroscience.

Markerless motion estimation for motion-compensated clinical brain imaging.

Motion-compensated brain imaging can dramatically reduce the artifacts and quantitative degradation associated with voluntary and involuntary subject head motion during positron emission tomography (PET), single photon emission computed tomography (SPECT) and computed tomography (CT). However, motion-compensated imaging protocols are not in widespread clinical use for these modalities. A key reason for this seems to be the lack of a practical motion tracking technology that allows for smooth and reliable integration of motion-compensated imaging protocols in the clinical setting. We seek to address this problem by investigating the feasibility of a highly versatile optical motion tracking method for PET, SPECT and CT geometries. The method requires no attached markers, relying exclusively on the detection and matching of distinctive facial features. We studied the accuracy of this method in 16 volunteers in a mock imaging scenario by comparing the estimated motion with an accurate marker-based method used in applications such as image guided surgery. A range of techniques to optimize performance of the method were also studied. Our results show that the markerless motion tracking method is highly accurate (<2 mm discrepancy against a benchmarking system) on an ethnically diverse range of subjects and, moreover, exhibits lower jitter and estimation of motion over a greater range than some marker-based methods. Our optimization tests indicate that the basic pose estimation algorithm is very robust but generally benefits from rudimentary background masking. Further marginal gains in accuracy can be achieved by accounting for non-rigid motion of features. Efficiency gains can be achieved by capping the number of features used for pose estimation provided that these features adequately sample the range of head motion encountered in the study. These proof-of-principle data suggest that markerless motion tracking is amenable to motion-compensated brain imaging and holds good promise for a practical implementation in clinical PET, SPECT and CT systems.

Open-field mouse brain PET: design optimisation and detector characterisation.

'Open-field' PET, in which an animal is free to move within an enclosed space during imaging, is a very promising advance for neuroscientific research. It provides a key advantage over conventional imaging under anesthesia by enabling functional changes in the brain to be correlated with an animal's behavioural response to environmental or pharmacologic stimuli. Previously we have demonstrated the feasibility of open-field imaging of rats using motion compensation techniques applied to a commercially available PET scanner. However, this approach of 'retro-fitting' motion compensation techniques to an existing system is limited by the inherent geometric and performance constraints of the system. The goal of this project is to develop a purpose-built PET scanner with geometry, motion tracking and imaging performance tailored and optimised for open-field imaging of the mouse brain. The design concept is a rail-based sliding tomograph which moves according to the animal's motion. Our specific aim in this work was to evaluate candidate scanner designs and characterise the performance of a depth-of-interaction detector module for the open-field system. We performed Monte Carlo simulations to estimate and compare the sensitivity and spatial resolution performance of four scanner geometries: a ring, parallel plate, and two box variants. Each system was based on a detector block consisting of a 23 × 23 array of 0.785 × 0.785 × 20 mm3 LSO crystals (overall dim. 19.6 × 19.6 × 20 mm). We found that a DoI resolution capability of 3 mm was necessary to achieve approximately uniform sub-millimetre spatial resolution throughout the FoV for all scanners except the parallel-plate geometry. With this DoI performance, the sensitivity advantage afforded by the box geometry with overlapping panels (16% peak absolute sensitivity, a 36% improvement over the ring design) suggests this unconventional design is best suited for imaging the mouse brain. We also built and characterised the block detector modelled in the simulations, including a dual-ended readout based on 6 × 6 arrays of through-silicon-via silicon photomultipliers (active area 84%) for DoI estimation. Identification of individual crystals in the flood map was excellent, energy resolution varied from 12.4% ± 0.6% near the centre to 24.4% ± 3.4% at the ends of the crystal, and the average DoI resolution was 2.8 mm ± 0.35 mm near the central depth (10 mm) and 3.5 mm ± 1.0 mm near the ends. Timing resolution was 1.4 ± 0.14 ns. Therefore, the DoI detector module meets the target specifications for the application and will be used as the basis for a prototype open-field mouse PET scanner.

Determining Glucose Metabolism Kinetics Using 18F-FDG Micro-PET/CT.

This paper describes the use of 18F-FDG and micro-PET/CT imaging to determine in vivo glucose metabolism kinetics in mice (and is transferable to rats). Impaired uptake and metabolism of glucose in multiple organ systems due to insulin resistance is a hallmark of type 2 diabetes. The ability of this technique to extract an image-derived input function from the vena cava using an iterative deconvolution method eliminates the requirement of the collection of arterial blood samples. Fitting of tissue and vena cava time activity curves to a two-tissue, three compartment model permits the estimation of kinetic micro-parameters related to the 18F-FDG uptake from the plasma to the intracellular space, the rate of transport from intracellular space to plasma and the rate of 18F-FDG phosphorylation. This methodology allows for multiple measures of glucose uptake and metabolism kinetics in the context of longitudinal studies and also provides insights into the efficacy of therapeutic interventions.

Motion compensation using origin ensembles in awake small animal positron emission tomography.

In emission tomographic imaging, the stochastic origin ensembles algorithm provides unique information regarding the detected counts given the measured data. Precision in both voxel and region-wise parameters may be determined for a single data set based on the posterior distribution of the count density allowing uncertainty estimates to be allocated to quantitative measures. Uncertainty estimates are of particular importance in awake animal neurological and behavioral studies for which head motion, unique for each acquired data set, perturbs the measured data. Motion compensation can be conducted when rigid head pose is measured during the scan. However, errors in pose measurements used for compensation can degrade the data and hence quantitative outcomes. In this investigation motion compensation and detector resolution models were incorporated into the basic origin ensembles algorithm and an efficient approach to computation was developed. The approach was validated against maximum liklihood-expectation maximisation and tested using simulated data. The resultant algorithm was then used to analyse quantitative uncertainty in regional activity estimates arising from changes in pose measurement precision. Finally, the posterior covariance acquired from a single data set was used to describe correlations between regions of interest providing information about pose measurement precision that may be useful in system analysis and design. The investigation demonstrates the use of origin ensembles as a powerful framework for evaluating statistical uncertainty of voxel and regional estimates. While in this investigation rigid motion was considered in the context of awake animal PET, the extension to arbitrary motion may provide clinical utility where respiratory or cardiac motion perturb the measured data.

List-mode image reconstruction for positron emission tomography using tetrahedral voxels.

Image space decomposition based on tetrahedral voxels are interesting candidates for use in emission tomography. Tetrahedral voxels provide many of the advantages of point clouds with irregular spacing, such as being intrinsically multi-resolution, yet they also serve as a volumetric partition of the image space and so are comparable to more standard cubic voxels. Additionally, non-rigid displacement fields can be applied to the tetrahedral mesh in a straight-forward manner. So far studies incorporating tetrahedral decomposition of the image space have concentrated on pre-calculated, node-based, system matrix elements which reduces the flexibility of the tetrahedral approach and the capacity to accurately define regions of interest. Here, a list-mode on-the-fly calculation of the system matrix elements is described using a tetrahedral decomposition of the image space and volumetric elements-voxels. The algorithm is demonstrated in the context of awake animal PET which may require both rigid and non-rigid motion compensation, as well as quantification within small regions of the brain. This approach allows accurate, event based, motion compensation including non-rigid deformations.

In vivo PET imaging with [(18)F]FDG to explain improved glucose uptake in an apolipoprotein A-I treated mouse model of diabetes.

AIMS/HYPOTHESIS: Type 2 diabetes is characterised by decreased HDL levels, as well as the level of apolipoprotein A-I (apoA-I), the main apolipoprotein of HDLs. Pharmacological elevation of HDL and apoA-I levels is associated with improved glycaemic control in patients with type 2 diabetes. This is partly due to improved glucose uptake in skeletal muscle. METHODS: This study used kinetic modelling to investigate the impact of increasing plasma apoA-I levels on the metabolism of glucose in the db/db mouse model. RESULTS: Treatment of db/db mice with apoA-I for 2 h significantly improved both glucose tolerance (AUC 2574 ± 70 mmol/l × min vs 2927 ± 137 mmol/l × min, for apoA-I and PBS, respectively; p < 0.05) and insulin sensitivity (AUC 388.8 ± 23.8 mmol/l × min vs 194.1 ± 19.6 mmol/l × min, for apoA-I and PBS, respectively; p < 0.001). ApoA-I treatment also increased glucose uptake by skeletal muscle in both an insulin-dependent and insulin-independent manner as evidenced by increased uptake of fludeoxyglucose ([(18)F]FDG) from plasma into gastrocnemius muscle in apoA-I treated mice, both in the absence and presence of insulin. Kinetic modelling revealed an enhanced rate of insulin-mediated glucose phosphorylation (k 3) in apoA-I treated mice (3.5 ± 1.1 × 10(-2) min(-1) vs 2.3 ± 0.7 × 10(-2) min(-1), for apoA-I and PBS, respectively; p < 0.05) and an increased influx constant (3.7 ± 0.6 × 10(-3) ml min(-1) g(-1) vs 2.0 ± 0.3 × 10(-3) ml min(-1) g(-1), for apoA-I and PBS, respectively; p < 0.05). Treatment of L6 rat skeletal muscle cells with apoA-I for 2 h indicated that increased hexokinase activity mediated the increased rate of glucose phosphorylation. CONCLUSIONS/INTERPRETATION: These findings indicate that apoA-I improves glucose disposal in db/db mice by improving insulin sensitivity and enhancing glucose phosphorylation.

4D PET iterative deconvolution with spatiotemporal regularization for quantitative dynamic PET imaging.

Quantitative measurements in dynamic PET imaging are usually limited by the poor counting statistics particularly in short dynamic frames and by the low spatial resolution of the detection system, resulting in partial volume effects (PVEs). In this work, we present a fast and easy to implement method for the restoration of dynamic PET images that have suffered from both PVE and noise degradation. It is based on a weighted least squares iterative deconvolution approach of the dynamic PET image with spatial and temporal regularization. Using simulated dynamic [(11)C] Raclopride PET data with controlled biological variations in the striata between scans, we showed that the restoration method provides images which exhibit less noise and better contrast between emitting structures than the original images. In addition, the method is able to recover the true time activity curve in the striata region with an error below 3% while it was underestimated by more than 20% without correction. As a result, the method improves the accuracy and reduces the variability of the kinetic parameter estimates calculated from the corrected images. More importantly it increases the accuracy (from less than 66% to more than 95%) of measured biological variations as well as their statistical detectivity.

Impact of extraneous mispositioned events on motion-corrected brain SPECT images of freely moving animals.

PURPOSE: Single photon emission computed tomography (SPECT) brain imaging of freely moving small animals would allow a wide range of important neurological processes and behaviors to be studied, which are normally inhibited by anesthetic drugs or precluded due to the animal being restrained. While rigid body motion of the head can be tracked and accounted for in the reconstruction, activity in the torso may confound brain measurements, especially since motion of the torso is more complex (i.e., nonrigid) and not well correlated with that of the head. The authors investigated the impact of mispositioned events and attenuation due to the torso on the accuracy of motion corrected brain images of freely moving mice. METHODS: Monte Carlo simulations of a realistic voxelized mouse phantom and a dual compartment phantom were performed. Each phantom comprised a target and an extraneous compartment which were able to move independently of each other. Motion correction was performed based on the known motion of the target compartment only. Two SPECT camera geometries were investigated: a rotating single head detector and a stationary full ring detector. The effects of motion, detector geometry, and energy of the emitted photons (hence, attenuation) on bias and noise in reconstructed brain regions were evaluated. RESULTS: The authors observed two main sources of bias: (a) motion-related inconsistencies in the projection data and (b) the mismatch between attenuation and emission. Both effects are caused by the assumption that the orientation of the torso is difficult to track and model, and therefore cannot be conveniently corrected for. The motion induced bias in some regions was up to 12% when no attenuation effects were considered, while it reached 40% when also combined with attenuation related inconsistencies. The detector geometry (i.e., rotating vs full ring) has a big impact on the accuracy of the reconstructed images, with the full ring detector being more advantageous. CONCLUSIONS: Motion-induced inconsistencies in the projection data and attenuation/emission mismatch are the two main causes of bias in reconstructed brain images when there is complex motion. It appears that these two factors have a synergistic effect on the qualitative and quantitative accuracy of the reconstructed images.

Simulation-based optimisation of the PET data processing for partial saturation approach protocols.

Positron emission tomography (PET) with [(11)C]Raclopride is an important tool for studying dopamine D2 receptor expression in vivo. [(11)C]Raclopride PET binding experiments conducted using the Partial Saturation Approach (PSA) allow the estimation of receptor density (B(avail)) and the in vivo affinity appK(D). The PSA is a simple, single injection, single scan experimental protocol that does not require blood sampling, making it ideal for use in longitudinal studies. In this work, we generated a complete Monte Carlo simulated PET study involving two groups of scans, in between which a biological phenomenon was inferred (a 30% decrease of B(avail)), and used it in order to design an optimal data processing chain for the parameter estimation from PSA data. The impact of spatial smoothing, noise removal and image resolution recovery technique on the statistical detection was investigated in depth. We found that image resolution recovery using iterative deconvolution of the image with the system point spread function associated with temporal data denoising greatly improves the accuracy and the statistical reliability of detecting the imposed phenomenon. Before optimisation, the inferred B(avail) variation between the two groups was underestimated by 42% and detected in 66% of cases, while a false decrease of appK(D) by 13% was detected in more than 11% of cases. After optimisation, the calculated B(avail) variation was underestimated by only 3.7% and detected in 89% of cases, while a false slight increase of appK(D) by 3.7% was detected in only 2% of cases. We found during this investigation that it was essential to adjust a factor that accounts for difference in magnitude between the non-displaceable ligand concentrations measured in the target and in the reference regions, for different data processing pathways as this ratio was affected by different image resolutions.

Imaging capabilities of the Inveon SPECT system using single-and multipinhole collimators.

UNLABELLED: The Inveon small-animal SPECT system comes with several types of multipinhole collimator plates. We evaluate here the performance measurements of the Inveon SPECT system using 6 different collimators: 3 dedicated for mouse imaging and 3 for rat imaging. METHODS: The measured performance parameters include the sensitivity, the spatial resolution using line sources, the ultra-micro Derenzo phantom, the recovery coefficient and the noise measurements using the National Electrical Manufacturers Association NU-4 image quality phantom, obtained with the 2 reconstruction algorithms available with the Inveon Acquisition Workplace, version 1.5-the 3-dimensional ordered-subset expectation maximization (3DOSEM) and the 3-dimensional maximum a posteriori (3DMAP). Further, the overall performance of the system is illustrated by an animal experiment. RESULTS: The results show that the Inveon SPECT scanner offers a spatial resolution, measured at the center of the field of view, ranging from 0.6 to 1 mm with the collimator plates dedicated to mouse imaging and from 1.2 to less than 2 mm with rat collimator plates. The system sensitivity varies from 29 to 404 cps/MBq for mouse collimators and from 53 to 175 cps/MBq for rat collimators. The image quality study showed that 3DMAP allows better noise reduction while preserving the recovery coefficient, compared with other regularization strategies such as the premature termination of the 3DOSEM reconstruction or 3DOSEM followed by gaussian filtering. CONCLUSION: The acquisition parameters, such as the collimator set and the radius of rotation, offer a wide range of possibilities to apply to a large number of biologic studies. However, special care must be taken because this increase in sensitivity can be offset by image degradation, such as image artifacts caused by projection overlap and statistical noise due to a higher number of iterations required for convergence. 3DMAP allowed better noise reduction while maintaining relatively constant recovery coefficients, as compared with other reconstruction strategies.