Wencke Lehnert

Characterisation of partial volume effect and region-based correction in small animal positron emission tomography (PET) of the rat brain

Accurate quantification of PET imaging data is required for a useful interpretation of the measured radioactive tracer concentrations. The partial volume effect (PVE) describes signal dilution and mixing due to spatial resolution and sampling limitations, which introduces bias in quantitative results. In the present study we investigated the magnitude of PVE for volumes of interest (VOIs) in the rat brain and the effect of positron range. In simulated (11)C-raclopride studies we examined the influence of PVE on time activity curves in striatal and cerebellar VOIs and binding potential estimation. The performance of partial volume correction (PVC) was studied using the region-based geometric transfer matrix (GTM) method including the question of whether a spatially variant point spread function (PSF) is necessary for PVC of a rat brain close to the centre of the field of view. Furthermore, we determined the effect of spillover from activity outside the brain. The results confirmed that PVE is significant in rat brain PET and showed that positron range is an important factor that needs to be included in the PSF. There was considerable bias in time activity curves for the simulated (11)C-raclopride studies and significant underestimation of binding potential even for very small centred VOIs. Good activity recovery was achieved with the GTM PVC using a spatially invariant simulated PSF when no activity was present outside the brain. PVC using a simple Gaussian fit point spread function was not sufficiently accurate. Spillover from regions outside the brain had a significant impact on measured activity concentrations and reduced the accuracy of PVC with the GTM method using rat brain regions alone, except for the smallest VOI size but at the cost of increased noise. Voxel-based partial volume correction methods which inherently compensate for spillover from outside the brain might be a more suitable choice.

Evaluation of transmission methodology and attenuation correction for the microPET Focus 220 animal scanner

An accurate, low noise estimate of photon attenuation in the subject is required for quantitative microPET studies of molecular tracer distributions in vivo. In this work, several transmission-based measurement techniques were compared, including coincidence mode with and without rod windowing, singles mode with two different energy sources ((68)Ge and (57)Co), and postinjection transmission scanning. In addition, the effectiveness of transmission segmentation and the propagation of transmission bias and noise into the emission images were examined. The (57)Co singles measurements provided the most accurate attenuation coefficients and superior signal-to-noise ratio, while (68)Ge singles measurements were degraded due to scattering from the object. Scatter correction of (68)Ge transmission data improved the accuracy for a 10 cm phantom but over-corrected for a mouse phantom. (57)Co scanning also resulted in low bias and noise in postinjection transmission scans for emission activities up to 20 MBq. Segmentation worked most reliably for transmission data acquired with (57)Co but the minor improvement in accuracy of attenuation coefficients and signal-to-noise may not justify its use, particularly for small subjects. We conclude that (57)Co singles transmission scanning is the most suitable method for measured attenuation correction on the microPET Focus 220 animal scanner.

Analytical positron range modelling in heterogeneous media for PET Monte Carlo simulation

Monte Carlo simulation codes that model positron interactions along their tortuous path are expected to be accurate but are usually slow. A simpler and potentially faster approach is to model positron range from analytical annihilation density distributions. The aims of this paper were to efficiently implement and validate such a method, with the addition of medium heterogeneity representing a further challenge. The analytical positron range model was evaluated by comparing annihilation density distributions with those produced by the Monte Carlo simulator GATE and by quantitatively analysing the final reconstructed images of Monte Carlo simulated data. In addition, the influence of positronium formation on positron range and hence on the performance of Monte Carlo simulation was investigated. The results demonstrate that 1D annihilation density distributions for different isotope-media combinations can be fitted with Gaussian functions and hence be described by simple look-up-tables of fitting coefficients. Together with the method developed for simulating positron range in heterogeneous media, this allows for efficient modelling of positron range in Monte Carlo simulation. The level of agreement of the analytical model with GATE depends somewhat on the simulated scanner and the particular research task, but appears to be suitable for lower energy positron emitters, such as (18)F or (11)C. No reliable conclusion about the influence of positronium formation on positron range and simulation accuracy could be drawn.

NEMA NU 4-2008 validation and applications of the PET-SORTEO Monte Carlo simulations platform for the geometry of the Inveon PET preclinical scanner

Monte Carlo-based simulation of positron emission tomography (PET) data plays a key role in the design and optimization of data correction and processing methods. Our first aim was to adapt and configure the PET-SORTEO Monte Carlo simulation program for the geometry of the widely distributed Inveon PET preclinical scanner manufactured by Siemens Preclinical Solutions. The validation was carried out against actual measurements performed on the Inveon PET scanner at the Australian Nuclear Science and Technology Organisation in Australia and at the Brain & Mind Research Institute and by strictly following the NEMA NU 4-2008 standard. The comparison of simulated and experimental performance measurements included spatial resolution, sensitivity, scatter fraction and count rates, image quality and Derenzo phantom studies. Results showed that PET-SORTEO reliably reproduces the performances of this Inveon preclinical system. In addition, imaging studies showed that the PET-SORTEO simulation program provides raw data for the Inveon scanner that can be fully corrected and reconstructed using the same programs as for the actual data. All correction techniques (attenuation, scatter, randoms, dead-time, and normalization) can be applied on the simulated data leading to fully quantitative reconstructed images. In the second part of the study, we demonstrated its ability to generate fast and realistic biological studies. PET-SORTEO is a workable and reliable tool that can be used, in a classical way, to validate and/or optimize a single PET data processing step such as a reconstruction method. However, we demonstrated that by combining a realistic simulated biological study ([(11)C]Raclopride here) involving different condition groups, simulation allows one also to assess and optimize the data correction, reconstruction and data processing line flow as a whole, specifically for each biological study, which is our ultimate intent.

Correction for continuous motion in small animal PET

In small animal PET imaging experiments, animals are generally required to be anaesthetized to avoid motion artifacts. However, anaesthesia can alter biochemical pathways within the brain, thus affecting the physiological parameters under investigation. The ability to image conscious animals would overcome this problem and open up the possibility of entirely new investigational paradigms.

High-resolution imaging of the large non-human primate brain using microPET: a feasibility study

The neuroanatomy and physiology of the baboon brain closely resembles that of the human brain and is well suited for evaluating promising new radioligands in non-human primates by PET and SPECT prior to their use in humans. These studies are commonly performed on clinical scanners with 5 mm spatial resolution at best, resulting in sub-optimal images for quantitative analysis. This study assessed the feasibility of using a microPET animal scanner to image the brains of large non-human primates, i.e. papio hamadryas (baboon) at high resolution. Factors affecting image accuracy, including scatter, attenuation and spatial resolution, were measured under conditions approximating a baboon brain and using different reconstruction strategies. Scatter fraction measured 32% at the centre of a 10 cm diameter phantom. Scatter correction increased image contrast by up to 21% but reduced the signal-to-noise ratio. Volume resolution was superior and more uniform using maximum a posteriori (MAP) reconstructed images (3.2-3.6 mm(3) FWHM from centre to 4 cm offset) compared to both 3D ordered subsets expectation maximization (OSEM) (5.6-8.3 mm(3)) and 3D reprojection (3DRP) (5.9-9.1 mm(3)). A pilot (18)F-2-fluoro-2-deoxy-d-glucose ([(18)F]FDG) scan was performed on a healthy female adult baboon. The pilot study demonstrated the ability to adequately resolve cortical and sub-cortical grey matter structures in the baboon brain and improved contrast when images were corrected for attenuation and scatter and reconstructed by MAP. We conclude that high resolution imaging of the baboon brain with microPET is feasible with appropriate choices of reconstruction strategy and corrections for degrading physical effects. Further work to develop suitable correction algorithms for high-resolution large primate imaging is warranted.

Iterative-based Partial Volume Effects correction with wavelet-based regularization for quantitative PET imaging

Two important technical limitations hampering quantitative measurements with dynamic PET imaging are 1) the limited spatial resolution of the detection system which induces quantitative biases due to Partial Volume Effects and 2), the poor counting statistics in the individual time frames which challenges further the subsequent kinetic modeling and analysis. In this work, we present an original method for the restoration of dynamic PET images that had suffered from both the consequences of the limited spatial resolution and the noise processes, which is based on the weighted least square iterative deconvolution in the wavelet space with temporal regularization of the wavelet coefficients. The solution image exhibits less noise, better contrasts between emitting structures and should therefore allow a better quantification compared with no correction‥

Comparative study of partial volume correction methods in small animal positron emission tomography (PET) of the rat brain

Quantitative accuracy in rat brain PET studies is reduced by partial volume effect. We investigated the performance of partial volume correction (PVC) in a realistic situation where activity is also taken up in the head and spills into the brain. The PVC approaches studied include the region-based geometric transfer matrix (GTM) method and voxel-based iterative deconvolution (reblurred Van Cittert and Richardson-Lucy). 8 realizations of dynamic rat brain PET studies of 11C-Raclopride with a binding potential BPND=3 in the striatum were simulated with the Monte Carlo simulator PET SORTEO. Synthetic time activity curves (TACs) were assigned to the striatum, cerebellum, remaining brain and head regions outside the brain of a rat head phantom. Different sized volumes of interest (VOIs) were sampled ranging from the full anatomical region to smaller VOIs containing only voxels with at least 50%, 70% or 90% of the maximum activity. BPND was calculated for the striatum using the simplified reference tissue model with the cerebellum as the reference tissue. Without PVC the accuracy of BPND was very low for all VOI sizes with biases between −44.7% and −20.9%. PVC using the GTM method was only accurate for the smallest 90% VOI with a bias of −7.7% but the standard deviation increased to 4.2% compared to less than 1% for the larger VOIs. Good accuracy was achieved for both iterative deconvolution methods using the 50% VOI (bias less than 8%) with standard deviations of less than 1.8%. Thus, in the presence of activity uptake outside the brain, iterative deconvolution methods outperform the GTM method. We are currently implementing PVC with a spatially variant PSF to better compensate for non-uniformities of spatial resolution away from the centre of the field of view.

An investigation of partial volume effect and partial volume correction in small animal positron emission tomography (PET) of the rat brain

Partial volume correction (PVC) has been successfully applied to human PET data, where a range of methods has been used including the use of anatomical side information. The rat brain is expected to have low variability for animals of similar weight, thus making it possible to delineate volumes of interest (VOIs) on a stereotaxic atlas [1]. The aims of this study were to investigate the magnitude of partial volume effect (PVE) in small animal PET for different regions in the rat brain and to evaluate the performance of PVC based on the geometric transfer matrix method (GTM) [2] using anatomical regions drawn on a stereotaxic atlas. PVE estimates in terms of activity retention in each region and spill-over between regions were calculated by convolving each region with a measured spatially invariant point spread function. PVC was tested on dynamic microPET studies of the dopaminergic D2 receptor radioligand 11C-Raclopride which were simulated using PET SORTEO, a Monte Carlo based PET simulator [3]. The kinetics of striatum and remaining brain were simulated based on the simplified reference tissue model [4] using the cerebellum as the reference tissue. A significant amount of PVE is present in microPET rat brain studies with recovery of true VOI concentration being between 52% and 20%. In the simulated 11C-Raclopride study the uncorrected time activity curves showed up to 55% reduction in measured activity concentration and a bias in binding potential of up to −36%. Good activity recovery and improvement of binding potential estimation was achieved with PVC (−0.26% to −4.36% bias). We conclude that PVE has a substantial influence on rat brain studies and PVC should be used to improve quantitative accuracy. PVC using the adapted GTM method shows promising results.

Count Rate Performance of the MicroPET Focus 220 Animal Scanner in Singles Transmission Scanning Mode

Count rate loss in singles transmission scans due to dead time can decrease the accuracy of attenuation correction. In addition, for very low transmission source activities measured attenuation may be affected by noise and background radiation emitted by radioactive lutetium-176 in the scintillator material. The aims of this study were to investigate count rate performance in singles transmission scanning for the microPET Focus 220 animal scanner, to examine the effect of energy window width on noise, scatter and dead time, and to determine the optimal range of activity for accurate attenuation correction. Transmission measurements were performed with a decaying 99mTc point source and using wide (21%) and narrow (4%) energy windows. We observed count rate losses at the detector level and in the front end electronics during energy discrimination. Further losses emerged due to multiplexing at the detector head interface for activities higher than 150 MBq for the wide energy window. Substantial count rate losses during transfer of list mode data from the microPET to the PC were also observed for this condition. Lutetium-176 background caused a significant deviation of measured attenuation for activities lower than 10 MBq for both energy windows. No significant bias due to scatter was introduced when using the wide energy window. We conclude that accurate attenuation data can be obtained with single photon transmission source activity in the range 10 to 150 MBq without requiring deadtime correction.