F. Lamare

GATE: a simulation toolkit for PET and SPECT.

Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. This paper gives a detailed description of the design and development of GATE by the OpenGATE collaboration, whose continuing objective is to improve, document and validate GATE by simulating commercially available imaging systems for PET and SPECT. Large effort is also invested in the ability and the flexibility to model novel detection systems or systems still under design. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at http:/www-lphe.epfl.ch/GATE/. Two benchmarks developed for PET and SPECT to test the installation of GATE and to serve as a tutorial for the users are presented. Extensive validation of the GATE simulation platform has been started, comparing simulations and measurements on commercially available acquisition systems. References to those results are listed. The future prospects towards the gridification of GATE and its extension to other domains such as dosimetry are also discussed.

List-mode-based reconstruction for respiratory motion correction in PET using non-rigid body transformations

Respiratory motion in emission tomography leads to reduced image quality. Developed correction methodology has been concentrating on the use of respiratory synchronized acquisitions leading to gated frames. Such frames, however, are of low signal-to-noise ratio as a result of containing reduced statistics. In this work, we describe the implementation of an elastic transformation within a list-mode-based reconstruction for the correction of respiratory motion over the thorax, allowing the use of all data available throughout a respiratory motion average acquisition. The developed algorithm was evaluated using datasets of the NCAT phantom generated at different points throughout the respiratory cycle. List-mode-data-based PET-simulated frames were subsequently produced by combining the NCAT datasets with Monte Carlo simulation. A non-rigid registration algorithm based on B-spline basis functions was employed to derive transformation parameters accounting for the respiratory motion using the NCAT dynamic CT images. The displacement matrices derived were subsequently applied during the image reconstruction of the original emission list mode data. Two different implementations for the incorporation of the elastic transformations within the one-pass list mode EM (OPL-EM) algorithm were developed and evaluated. The corrected images were compared with those produced using an affine transformation of list mode data prior to reconstruction, as well as with uncorrected respiratory motion average images. Results demonstrate that although both correction techniques considered lead to significant improvements in accounting for respiratory motion artefacts in the lung fields, the elastic-transformation-based correction leads to a more uniform improvement across the lungs for different lesion sizes and locations.

Imaging intraplaque inflammation in carotid atherosclerosis with 11C-PK11195 positron emission tomography/computed tomography

AIMS We sought to determine whether intraplaque inflammation could be measured with positron emission tomography/computed tomography angiography (PET/CTA) using (11)C-PK11195, a selective ligand of the translocator protein (18 kDa) (TSPO) which is highly expressed by activated macrophages. METHODS AND RESULTS Patients (n = 32; mean age 70 ± 9 years) with carotid stenoses (n = 36; 9 symptomatic and 27 asymptomatic) underwent (11)C-PK11195 PET/CTA imaging. (11)C-PK11195 uptake into carotid plaques was measured using target-to-background ratios (TBR). On CTA images, plaque composition was assessed by measuring CT attenuation of the carotid plaque. Eight patients underwent carotid endarterectomy and ultrathin contiguous sections were processed for TSPO and CD68 (using immunohistochemical staining, (3)H-PK11195 autoradiography, and confocal fluorescence microscopy). Carotid plaques associated with ipsilateral symptoms (stroke or transient ischaemic attack) had higher TBR (1.06 ± 0.20 vs. 0.86 ± 0.11, P = 0.001) and lower CT attenuation [(median, inter-quartile range) 37, 24-40 vs. 71, 56-125 HU, P = 0.01] than those without. On immunohistochemistry and confocal fluorescence microscopy, CD68 and PBR co-localized with (3)H-PK11195 uptake at autoradiography. There was a significant correlation between (11)C-PK11195 TBR and autoradiographic percentage-specific binding (r = 0.77, P = 0.025). Both TBR and CT plaque attenuation had high negative predictive values (91 and 92%, respectively) for detecting symptomatic patients. However, the best positive predictive value (100%) was achieved when TBR and CT attenuation were combined. CONCLUSION Imaging intraplaque inflammation in vivo with (11)C-PK11195 PET/CTA is feasible and can distinguish between recently symptomatic and asymptomatic plaques. Patients with a recent ischaemic event had ipsilateral plaques with lower CT attenuation and increased (11)C-PK11195 uptake.

Respiratory motion correction for PET oncology applications using affine transformation of list mode data

Respiratory motion is a source of artefacts and reduced image quality in PET. Proposed methodology for correction of respiratory effects involves the use of gated frames, which are however of low signal-to-noise ratio. Therefore a method accounting for respiratory motion effects without affecting the statistical quality of the reconstructed images is necessary. We have implemented an affine transformation of list mode data for the correction of respiratory motion over the thorax. The study was performed using datasets of the NCAT phantom at different points throughout the respiratory cycle. List mode data based PET simulated frames were produced by combining the NCAT datasets with a Monte Carlo simulation. Transformation parameters accounting for respiratory motion were estimated according to an affine registration and were subsequently applied on the original list mode data. The corrected and uncorrected list mode datasets were subsequently reconstructed using the one-pass list mode EM (OPL-EM) algorithm. Comparison of corrected and uncorrected respiratory motion average frames suggests that an affine transformation in the list mode data prior to reconstruction can produce significant improvements in accounting for respiratory motion artefacts in the lungs and heart. However, the application of a common set of transformation parameters across the imaging field of view does not significantly correct the respiratory effects on organs such as the stomach, liver or spleen.

Imaging of Vascular Inflammation With [11C]-PK11195 and Positron Emission Tomography/Computed Tomography Angiography

OBJECTIVES We sought to investigate whether positron emission tomography/computed tomography (CT) angiography using [11C]-PK11195, a selective ligand for peripheral benzodiazepine receptors expressed in activated macrophages, can be used to image vascular inflammation. BACKGROUND Activated macrophages and T lymphocytes are fundamental elements in the pathogenesis of large-vessel vasculitides. METHODS Fifteen patients (age 52+/-16 years) with systemic inflammatory disorders (6 consecutive symptomatic patients with clinical suspicion of active vasculitis and 9 asymptomatic control patients) underwent positron emission tomography with [11C]-PK11195 and CT angiography. [11C]-PK11195 uptake was measured by calculating target-to-background ratios of activity normalized to venous blood. RESULTS Coregistration of positron emission tomography with contrast-enhanced CT angiography facilitated localization of [11C]-PK11195 arterial wall uptake. Visual analysis revealed focal [11C]-PK11195 uptake in the arterial wall of all 6 symptomatic patients, but in none of the asymptomatic controls. Although serum inflammatory biomarkers (C-reactive protein, erythrocyte sedimentation rate, white cell count) did not differ significantly between the 2 groups, symptomatic patients had increased [11C]-PK11195 vascular uptake (target-to-background ratio 2.41+/-1.59 vs. 0.98+/-0.10; p=0.001). CONCLUSIONS By binding to activated macrophages in the vessel wall, [11C]-PK11195 enables noninvasive imaging of vascular inflammation. Alternative longer-lived radioligands for probing peripheral benzodiazepine receptors are being tested for wider clinical applications.

Detection and Quantification of Large-Vessel Inflammation with 11C-(R)-PK11195 PET/CT

We investigated whether PET/CT angiography using 11C-(R)-PK11195, a selective ligand for the translocator protein (18 kDa) expressed in activated macrophages, could allow imaging and quantification of arterial wall inflammation in patients with large-vessel vasculitis. Methods: Seven patients with systemic inflammatory disorders (3 symptomatic patients with clinical suspicion of active vasculitis and 4 asymptomatic patients) underwent PET with 11C-(R)-PK11195 and CT angiography to colocalize arterial wall uptake of 11C-(R)-PK11195. Tissue regions of interest were defined in bone marrow, lung parenchyma, wall of the ascending aorta, aortic arch, and descending aorta. Blood-derived and image-derived input functions (IFs) were generated. A reversible 1-tissue compartment with 2 kinetic rate constants and a fractional blood volume term were used to fit the time–activity curves to calculate total volume of distribution (VT). The correlation between VT and standardized uptake values was assessed. Results: VT was significantly higher in symptomatic than in asymptomatic patients using both image-derived total plasma IF (0.55 ± 0.15 vs. 0.27 ± 0.12, P = 0.009) and image-derived parent plasma IF (1.40 ± 0.50 vs. 0.58 ± 0.25, P = 0.018). A good correlation was observed between VT and standardized uptake value (R = 0.79; P = 0.03). Conclusion: 11C-(R)-PK11195 imaging allows visualization of macrophage infiltration in inflamed arterial walls. Tracer uptake can be quantified with image-derived IF without the need for metabolite corrections and evaluated semiquantitatively with standardized uptake values.

Evaluation of respiratory and cardiac motion correction schemes in dual gated PET/CT cardiac imaging

PURPOSE Cardiac imaging suffers from both respiratory and cardiac motion. One of the proposed solutions involves double gated acquisitions. Although such an approach may lead to both respiratory and cardiac motion compensation there are issues associated with (a) the combination of data from cardiac and respiratory motion bins, and (b) poor statistical quality images as a result of using only part of the acquired data. The main objective of this work was to evaluate different schemes of combining binned data in order to identify the best strategy to reconstruct motion free cardiac images from dual gated positron emission tomography (PET) acquisitions. METHODS A digital phantom study as well as seven human studies were used in this evaluation. PET data were acquired in list mode (LM). A real-time position management system and an electrocardiogram device were used to provide the respiratory and cardiac motion triggers registered within the LM file. Acquired data were subsequently binned considering four and six cardiac gates, or the diastole only in combination with eight respiratory amplitude gates. PET images were corrected for attenuation, but no randoms nor scatter corrections were included. Reconstructed images from each of the bins considered above were subsequently used in combination with an affine or an elastic registration algorithm to derive transformation parameters allowing the combination of all acquired data in a particular position in the cardiac and respiratory cycles. Images were assessed in terms of signal-to-noise ratio (SNR), contrast, image profile, coefficient-of-variation (COV), and relative difference of the recovered activity concentration. RESULTS Regardless of the considered motion compensation strategy, the nonrigid motion model performed better than the affine model, leading to higher SNR and contrast combined with a lower COV. Nevertheless, when compensating for respiration only, no statistically significant differences were observed in the performance of the two motion models considered. Superior image SNR and contrast were seen using the affine respiratory motion model in combination with the diastole cardiac bin in comparison to the use of the whole cardiac cycle. In contrast, when simultaneously correcting for cardiac beating and respiration, the elastic respiratory motion model outperformed the affine model. In this context, four cardiac bins associated with eight respiratory amplitude bins seemed to be adequate. CONCLUSIONS Considering the compensation of respiratory motion effects only, both affine and elastic based approaches led to an accurate resizing and positioning of the myocardium. The use of the diastolic phase combined with an affine model based respiratory motion correction may therefore be a simple approach leading to significant quality improvements in cardiac PET imaging. However, the best performance was obtained with the combined correction for both cardiac and respiratory movements considering all the dual-gated bins independently through the use of an elastic model based motion compensation.

A posteriori respiratory motion gating of dynamic PET images

The presence of patient physiological motion during imaging may cause significant artifacts in image quality. Proposed correction methodologies involve the use of gated acquisitions through simultaneous recording of an external signal. The purpose of our work is to determine the feasibility of post-acquisition synchronization of dynamically acquired PET images in the absence of any external signal. The principle of the technique is based on the assumption that although the amplitude of the motion may vary from pixel to pixel inside the same organ, the frequency of the periodic motion is the same. Under such conditions, the prerequisite for a posteriori gating is the ability to accurately estimate that frequency. We performed simulation studies using the NCAT phantom and a Monte Carlo simulation of the GE Advance PET system (3D mode of operation). A number of NCAT emission and the corresponding transmission frames were generated throughout a respiratory cycle. Time frames of 0.15, 0.45 and 0.62 seconds were simulated with variable count statistics (namely 30k, 70k and 120k of total simulated coincidences). Time activity curves were obtained, for each of the dynamic series formed, using different ROIs and Fourier transform was performed in order to estimate the frequency of the simulated motion. We were able to determine the frequency of motion (within 2% of the simulated frequency) for all three frame time durations evaluated. Using the estimated frequency we were able to calculate on a pixel by pixel basis the amplitude and the phase of the motion, allowing us to reconstruct an a posteriori gated time series.

Super-Resolution in Respiratory Synchronized Positron Emission Tomography

Respiratory motion is a major source of reduced quality in positron emission tomography (PET). In order to minimize its effects, the use of respiratory synchronized acquisitions, leading to gated frames, has been suggested. Such frames, however, are of low signal-to-noise ratio (SNR) as they contain reduced statistics. Super-resolution (SR) techniques make use of the motion in a sequence of images in order to improve their quality. They aim at enhancing a low-resolution image belonging to a sequence of images representing different views of the same scene. In this work, a maximum a posteriori (MAP) super-resolution algorithm has been implemented and applied to respiratory gated PET images for motion compensation. An edge preserving Huber regularization term was used to ensure convergence. Motion fields were recovered using a B-spline based elastic registration algorithm. The performance of the SR algorithm was evaluated through the use of both simulated and clinical datasets by assessing image SNR, as well as the contrast, position and extent of the different lesions. Results were compared to summing the registered synchronized frames on both simulated and clinical datasets. The super-resolution image had higher SNR (by a factor of over 4 on average) and lesion contrast (by a factor of 2) than the single respiratory synchronized frame using the same reconstruction matrix size. In comparison to the motion corrected or the motion free images a similar SNR was obtained, while improvements of up to 20% in the recovered lesion size and contrast were measured. Finally, the recovered lesion locations on the SR images were systematically closer to the true simulated lesion positions. These observations concerning the SNR, lesion contrast and size were confirmed on two clinical datasets included in the study. In conclusion, the use of SR techniques applied to respiratory motion synchronized images lead to motion compensation combined with improved image SNR and contrast, without any increase in the overall acquisition times.

Generation of 4-Dimensional CT Images Based on 4-Dimensional PET–Derived Motion Fields

Respiratory motion can potentially reduce accuracy in anatomic and functional image fusion from multimodality systems. It can blur the uptake of small lesions and lead to significant activity underestimation. Solutions presented to date include respiration-synchronized anatomic and functional acquisitions. To increase the signal-to-noise ratio of the synchronized PET images, methods using nonrigid transformations during the reconstruction process have been proposed. In most of these methods, 4-dimensional (4D) CT images were used to derive the required deformation matrices. However, variations between acquired 4D PET and corresponding CT image series due to differences in respiratory conditions during PET and CT acquisitions have been reported. In addition, the radiation dose burden resulting from a 4D CT acquisition may not be justifiable for every patient. Methods: In this paper, we present a method for the generation of dynamic CT images from the combination of one reference CT image and deformation matrices obtained from the elastic registration of 4D PET images not corrected for attenuation. On the one hand, our approach eliminates the need for the acquisition of dynamic CT. On the other hand, it also ensures a good match between CT and PET images, allowing accurate attenuation correction to be performed for respiration-synchronized PET acquisitions. Results: The proposed method was first validated on Monte Carlo–simulated datasets, and then on patient datasets (n = 4) by comparing generated 4D CT images with the corresponding acquired original CT images. Different levels of PET image statistical quality were considered in order to investigate the impact of image noise in the derivation of the 4D CT series. Conclusion: Our results suggest that clinically relevant PET acquisition times can be used for the implementation of such an approach, making this an even more attractive solution considering the absence of the extra dose given by a standard 4D CT acquisition. Finally, this approach may be applicable to other multimodality devices such as PET/MR.