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STIR: software for tomographic image reconstruction release 2

We present an update to STIR, an Open Source object-oriented library in C++ for 3D PET reconstruction. This library has been designed so that it can be used for many algorithms and scanner geometries, while being portable to various computing platforms. This second release enhances its flexibility and modular design, but also adds extra capabilities such as list mode reconstruction, more data formats etc.

Geometrical and Monte Carlo projectors in 3D PET reconstruction

PURPOSE In the present work, the authors compare geometrical and Monte Carlo projectors in detail. The geometrical projectors considered were the conventional geometrical Siddon ray-tracer (S-RT) and the orthogonal distance-based ray-tracer (OD-RT), based on computing the orthogonal distance from the center of image voxel to the line-of-response. A comparison of these geometrical projectors was performed using different point spread function (PSF) models. The Monte Carlo-based method under consideration involves an extensive model of the system response matrix based on Monte Carlo simulations and is computed off-line and stored on disk. METHODS Comparisons were performed using simulated and experimental data of the commercial small animal PET scanner rPET. RESULTS The results demonstrate that the orthogonal distance-based ray-tracer and Siddon ray-tracer using PSF image-space convolutions yield better images in terms of contrast and spatial resolution than those obtained after using the conventional method and the multiray-based S-RT. Furthermore, the Monte Carlo-based method yields slight improvements in terms of contrast and spatial resolution with respect to these geometrical projectors. CONCLUSIONS The orthogonal distance-based ray-tracer and Siddon ray-tracer using PSF image-space convolutions represent satisfactory alternatives to factorizing the system matrix or to the conventional on-the-fly ray-tracing methods for list-mode reconstruction, where an extensive modeling based on Monte Carlo simulations is unfeasible.

Quantification of dopaminergic neurotransmission SPECT studies with 123I-labelled radioligands. A comparison between different imaging systems and data acquisition protocols using Monte Carlo simulation

Purpose123I-labelled radioligands are commonly used for single-photon emission computed tomography (SPECT) imaging of the dopaminergic system to study the dopamine transporter binding. The aim of this work was to compare the quantitative capabilities of two different SPECT systems through Monte Carlo (MC) simulation.MethodsThe SimSET MC code was employed to generate simulated projections of a numerical phantom for two gamma cameras equipped with a parallel and a fan-beam collimator, respectively. A fully 3D iterative reconstruction algorithm was used to compensate for attenuation, the spatially variant point spread function (PSF) and scatter. A post-reconstruction partial volume effect (PVE) compensation was also developed.ResultsFor both systems, the correction for all degradations and PVE compensation resulted in recovery factors of the theoretical specific uptake ratio (SUR) close to 100%. For a SUR value of 4, the recovered SUR for the parallel imaging system was 33% for a reconstruction without corrections (OSEM), 45% for a reconstruction with attenuation correction (OSEM-A), 56% for a 3D reconstruction with attenuation and PSF corrections (OSEM-AP), 68% for OSEM-AP with scatter correction (OSEM-APS) and 97% for OSEM-APS plus PVE compensation (OSEM-APSV). For the fan-beam imaging system, the recovered SUR was 41% without corrections, 55% for OSEM-A, 65% for OSEM-AP, 75% for OSEM-APS and 102% for OSEM-APSV.ConclusionOur findings indicate that the correction for degradations increases the quantification accuracy, with PVE compensation playing a major role in the SUR quantification. The proposed methodology allows us to reach similar SUR values for different SPECT systems, thereby allowing a reliable standardisation in multicentric studies.

A new seipin-associated neurodegenerative syndrome

Background Seipin/BSCL2 mutations can cause type 2 congenital generalised lipodystrophy (BSCL) or dominant motor neurone diseases. Type 2 BSCL is frequently associated with some degree of intellectual impairment, but not to fatal neurodegeneration. In order to unveil the aetiology and pathogenetic mechanisms of a new neurodegenerative syndrome associated with a novel BSCL2 mutation, six children, four of them showing the BSCL features, were studied. Methods Mutational and splicing analyses of BSCL2 were performed. The brain of two of these children was examined postmortem. Relative expression of BSCL2 transcripts was analysed by real-time reverse transcription-polymerase chain reaction (RT-PCR) in different tissues of the index case and controls. Overexpressed mutated seipin in HeLa cells was analysed by immunofluorescence and western blotting. Results Two patients carried a novel homozygous c.985C>T mutation, which appeared in the other four patients in compound heterozygosity. Splicing analysis showed that the c.985C>T mutation causes an aberrant splicing site leading to skipping of exon 7. Expression of exon 7-skipping transcripts was very high with respect to that of the non-skipped transcripts in all the analysed tissues of the index case. Neuropathological studies showed severe neurone loss, astrogliosis and intranuclear ubiquitin(+) aggregates in neurones from multiple cortical regions and in the caudate nucleus. Conclusions Our results suggest that exon 7 skipping in the BSCL2 gene due to the c.985C>T mutation is responsible for a novel early onset, fatal neurodegenerative syndrome involving cerebral cortex and basal ganglia.

Evaluation of the single scatter simulation algorithm implemented in the STIR library

The model-based single scatter simulation (SSS) algorithm has been implemented in the Open Source software library called STIR (Software for Tomographic Image Reconstruction). The main advantage of the SSS algorithm is its good accuracy at small computational time. The aim of the current work is to validate our implementation and to investigate the influence of several parameters. The validation tests are based on the NEMA-NU 2001 standard about scatter accuracy. The results of our implementation are compared both with data from the SimSET Monte Carlo simulation package and with measured data. The flexibility of our code can help us to understand the influence of many parameters of the algorithm, such that optimal values can be found for given time constraints, as for example are the detector sampling and the voxel size of the transmission image. This implementation will be included in future distributions of STIR.

Comparative evaluation of scatter correction in 3D PET using different scatter-level approximations

ObjectiveIn 3D PET, scatter of the gamma photons is one of the most significant physical factors which degrades not only image quality but also quantification. The currently most used scatter estimation method is the analytic single scatter simulation (SSS) which usually accommodates for multiple scattering by scaling the single scatter estimation. However, it has not been clear yet how accurate this approximation is for cases where multiple scatter is significant, raising the question: “How important is correction for multiple scattered photons, and how accurately do we need to simulate all scattered events by appropriate scaling?” This study answers these questions and evaluates the accuracy of SSS implementation in the open-source library STIR.MethodsDifferent scatter orders approximations are evaluated including different levels of scattering and different scaling approaches using Monte Carlo (i.e. SimSET) data. SimSET simulations of a large anthropomorphic phantom were reconstructed with iterative reconstruction algorithms. Images reconstructed with 3D filtered back-projection reprojection algorithm have been compared quantitatively in order to clarify the errors due to different scatter order approximations.ResultsQuantification in regions has improved by scatter correction. For example, in the heart the ideal value was 3, whereas before scatter correction the standard uptake value (SUV) was 4.0, after single scatter correction was 3.3 and after single and double scatter correction was 3.0. After correction by scaling single scatter with tail-fit, the SUV was 3.1, whereas with total-fit it was 3.0. Similarly, for the SSS correction methodology implemented in STIR using tail-fit the heart SUV was 3.1 whereas using total-fit it was 3.0.ConclusionsThe results demonstrate that correction for double scatter improves image contrast and therefore it is required for the accurate estimation of activity distribution in PET imaging. However, it has been also shown that scaling the single scatter distribution is a reasonable approximation to compensate for total scatter. Finally, scatter correction with STIR has shown excellent agreement with Monte Carlo simulations.

PET/CT imaging of 3D printed devices in the gastrointestinal tract of rodents

Fused deposition modelling (FDM) 3D printing (3DP) is a revolutionary technology with the potential to transform drug product design in both the pre-clinical and clinical arena. The objective of this pilot study was to explore the intestinal behaviour of four different polymer-based devices fabricated using FDM 3DP technology in rats. Small capsular devices of 8.6 mm in length and 2.65 mm in diameter were printed from polyvinyl alcohol-polyethylene glycol graft-copolymer (PVA-PEG copolymer, Kollicoat IR), hydroxypropylcellulose (HPC, Klucel), ethylcellulose (EC, Aqualon N7) and hypromellose acetate succinate (HPMCAS, Aquasolve-LG). A smaller sized device, 3.2 mm in length and 2.65 mm in diameter, was also prepared with HPMCAS to evaluate the cut off size of gastric emptying of solid formulations in rats. The devices were radiolabelled with Fluorodeoxyglucose (18F-FDG) and small animal positron emission tomography/computed tomography (microPET/CT) was used to track the movement and disintegration of the fabricated devices in the rats. The PVA-PEG copolymer and HPC devices disintegrated after 60min following oral administration. The EC structures did not disintegrate in the gastrointestinal tracts of the rats, whereas the HPMCAS-based systems disintegrated after 420 min. Interestingly, it was noted that the devices which remained intact over the course of the study had not emptied from the stomach of the rats. This was also the case with the smaller sized device. In summary, we report for the first time, the use of a microPET/CT imaging technique to evaluate the in vivo behaviour of 3D printed formulations. The manipulation of the 3D printed device design could be used to fabricate dosage forms of varying sizes and geometries with better gastric emptying characteristics suitable for rodent administration. The increased understanding of the capabilities of 3DP in dosage form design could, henceforth, accelerate pre-clinical testing of new drug candidates in animal models.

Correction for FDG PET dose extravasations: Monte Carlo validation and quantitative evaluation of patient studies

PURPOSE Current procedure guidelines for whole body [18F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) state that studies with visible dose extravasations should be rejected for quantification protocols. Our work is focused on the development and validation of methods for estimating extravasated doses in order to correct standard uptake value (SUV) values for this effect in clinical routine. METHODS One thousand three hundred sixty-seven consecutive whole body FDG-PET studies were visually inspected looking for extravasation cases. Two methods for estimating the extravasated dose were proposed and validated in different scenarios using Monte Carlo simulations. All visible extravasations were retrospectively evaluated using a manual ROI based method. In addition, the 50 patients with higher extravasated doses were also evaluated using a threshold-based method. RESULTS Simulation studies showed that the proposed methods for estimating extravasated doses allow us to compensate the impact of extravasations on SUV values with an error below 5%. The quantitative evaluation of patient studies revealed that paravenous injection is a relatively frequent effect (18%) with a small fraction of patients presenting considerable extravasations ranging from 1% to a maximum of 22% of the injected dose. A criterion based on the extravasated volume and maximum concentration was established in order to identify this fraction of patients that might be corrected for paravenous injection effect. CONCLUSIONS The authors propose the use of a manual ROI based method for estimating the effectively administered FDG dose and then correct SUV quantification in those patients fulfilling the proposed criterion.

Assessment of SPM in Perfusion Brain SPECT Studies. A Numerical Simulation Study Using Bootstrap Resampling Methods

Statistical parametric mapping (SPM) has become the technique of choice to statistically evaluate positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and single photon emission computed tomography (SPECT) functional brain studies. Nevertheless, only a few methodological studies have been carried out to assess the performance of SPM in SPECT. The aim of this paper was to study the performance of SPM in detecting changes in regional cerebral blood flow (rCBF) in hypo- and hyperperfused areas in brain SPECT studies. The paper seeks to determine the relationship between the group size and the rCBF changes, and the influence of the correction for degradations. The assessment was carried out using simulated brain SPECT studies. Projections were obtained with Monte Carlo techniques, and a fan-beam collimator was considered in the simulation process. Reconstruction was performed by using the ordered subsets expectation maximization (OSEM) algorithm with and without compensation for attenuation, scattering, and spatial variant collimator response. Significance probability maps were obtained with SPM2 by using a one-tailed two-sample f-test. A bootstrap resampling approach was used to determine the sample size for SPM to detect the between-group differences. Our findings show that the correction for degradations results in a diminution of the sample size, which is more significant for small regions and low-activation factors. Differences in sample size were found between hypo- and hyperperfusion. These differences were larger for small regions and low-activation factors, and when no corrections were included in the reconstruction algorithm.

Integration of advanced 3D SPECT modeling into the open-source STIR framework

PURPOSE The Software for Tomographic Image Reconstruction (STIR, http://stir.sourceforge.net) package is an open source object-oriented library implemented in C++. Although its modular design is suitable for reconstructing data from several modalities, it currently only supports Positron Emission Tomography (PET) data. In this work, the authors present results for Single Photon Emission Computed Tomography (SPECT) imaging. METHODS This was achieved by the complete integration of a 3D SPECT system matrix modeling library into STIR. RESULTS The authors demonstrate the flexibility of the combined software by reconstructing simulated and acquired projections from three different scanners with different iterative algorithms of STIR. CONCLUSIONS The extension of the open source STIR project with advanced SPECT modeling will enable the research community to study the performance of several algorithms on SPECT data, and potentially implement new algorithms by expanding the existing framework.