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.

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GATE : a simulation toolkit for PET and SPECT

We review positron-emission tomography (PET), which has inherent advantages that avoid the shortcomings of other nuclear medicine imaging methods. PET image reconstruction methods with origins in signal and image processing are discussed, including the potential problems of these methods. A summary of statistical image reconstruction methods, which can yield improved image quality, is also presented.

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Positron-emission tomography

*Departments of Radiation Oncology* and Radiology,’ University of Washington, Seattle. WA Purpose: To assess pretreatment hypoxia in a variety of tumors using positron emission tomography (PET) after injection of the hypoxia-binding radiopharmaceutical [“‘F]fluoromisonidazoIe ([‘sF]FMISO). Methods and Materials: Tumor fractional hypoxic volume (FHV) was determined in 21 nonsmail ceII hmg cancer patients, 7 head and neck cancer patients, 4 prostate cancer patients, and 5 patients with other by quantitative PET imaging after injection of [‘*F]FMISO (0.1 mCi/kg). The FHV was defined as the proportion of pixels in the imaged tumor volume with a tissue:biood [‘*F] activity ratio 2 1.4 at 120-160 min postinjection. A FHV > 0 was taken as evidence for tumor hypoxia. Results: Hypoxia was observed in 36 of 37 tumors studied with FMISO PET inaging; FHVs ranged from 0 to 94.7%. In nonsmall cell lung cancers (n = 21), the median FHV was 47.6% and the range, 1.3 to 94.7%. There was no correlation between tumor size and FHV. In the seven head and neck carcinomas, the m&Ian FHV was 8.8% , with a range from 0.2 to 18.9%. In the group of four prostate cancers, the median and range were 18.2% and 0 to 93.9%, while in a group of five tumors of different types the median FHV was 55.2% (range: 21.4 to 85.8%). Conclusions: Hypoxia was present in 97% of the tumors studied and the extent of hypoxia varied markedly between tumors in the same site or of the same histology. Hypoxia also was distributed heterogeneously between regions within a single tumor. These results are consistent with O2 electrode measures with other types afhuman tumors. The intra- and intertumor variability indicate the importance of makhg oxygenation measures in individual tumors and the necessity to sample as much of the tumor volume as possible. Copyright 0 1996 Elsevie!

http://www.hyperbaricinformation.com/HBO-Articles/HBO-Radiation/Radiosensitization/Int-J-Radiation-Oncology-Biol-Phys-1996-36(2)-417-Rasey-Quan.pdf

Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: A pretherapy study of 37 patients

Significant improvements have made it possible to add the technology of time-of-flight (TOF) to improve PET, particularly for oncology applications. The goals of this work were to investigate the benefits of TOF in experimental phantoms and to determine how these benefits translate into improved performance for patient imaging. Methods: In this study we used a fully 3-dimensional scanner with the scintillator lutetium-yttrium oxyorthosilicate and a system timing resolution of ;600 ps. The data are acquired in list-mode and reconstructed with a maximum-likelihood expectation maximization algorithm; the system model includes the TOF kernel and corrections for attenuation, detector normalization, randoms, and scatter. The scatter correction is an extension of the model-based singlescatter simulation to include the time domain. Phantom measurements to study the benefit of TOF include 27-cm- and 35-cm-diameter distributions with spheres ranging in size from 10to37mm.ToassessthebenefitofTOFPETforclinicalimaging, patient studies are quantitatively analyzed. Results: The lesion phantom studies demonstrate the improved contrast of the smallest spheres with TOF compared with non-TOF and also confirm the faster convergence of contrast with TOF. These gains are evident from visual inspection of the images as well as a quantitative evaluation of contrast recovery of the spheres and noise in the background. The gains with TOF are higher for larger objects. These results correlate with patient studies in which lesions are seen more clearly and with higher uptake at comparable noise for TOF than with non-TOF. Conclusion: TOF leads to a better contrast-versus-noise trade-off than non-TOF but one that is difficult to quantify in terms of a simple sensitivity gain improvement: A single gain factor for TOF improvement does not include the increased rate of convergence with TOF nor does it consider that TOF may converge to a different contrast than non-TOF. The experimental phantom results agree with those of prior simulations and help explain the improved image quality with TOF for patient oncology studies.

https://jnm.snmjournals.org/content/jnumed/49/3/462.full.pdf

Benefit of Time-of-Flight in PET: Experimental and Clinical Results

The quality of images reconstructed by statistical iterative methods depends on an accurate model of the relationship between image space and projection space through the system matrix. The elements of the system matrix for the clinical Hi-Rez scanner were derived by processing the data measured for a point source at different positions in a portion of the field of view. These measured data included axial compression and azimuthal interleaving of adjacent projections. Measured data were corrected for crystal and geometrical efficiency. Then, a whole system matrix was derived by processing the responses in projection space. Such responses included both geometrical and detection physics components of the system matrix. The response was parameterized to correct for point source location and to smooth for projection noise. The model also accounts for axial compression (span) used on the scanner. The forward projector for iterative reconstruction was constructed using the estimated response parameters. This paper extends our previous work to fully three-dimensional. Experimental data were used to compare images reconstructed by the standard iterative reconstruction software and the one modeling the response function. The results showed that the modeling of the response function improves both spatial resolution and noise properties

Fully 3-D PET reconstruction with system matrix derived from point source measurements

This paper reviews the history and principles of Monte Carlo simulation, emphasizing techniques commonly used in the simulation of medical imaging.

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Introduction To Monte Carlo Simulation.

We are developing a software simulation system for emission tomography (SimSET). All the software is being designed and documented using modern software engineering techniques. As modules in the system are completed they will be placed in the public domain. The first module of SimSET to be released, the photon history generator (PHG), tracks photons through the tomograph field-of-view. The PHG incorporates importance sampling [I] and allows source activity and attenuation to be modeled as voxelized objects in three dimensions. The input format for the source object has been chosen to match the digitized anthropomorphic phantom of Zubal et a1 [2], allowing physiologically realistic phantoms to be easily simulated.

Preliminary Experience With The Photon History Generator Module Of A Public-domain Simulation System For Emission Tomography

Monte Carlo simulations are widely used to study the transmission and scattering of γ rays. Use of this method for simulations of emission tomographs suffers from geometric inefficiency resulting from the low solid angle of acceptance of most tomograph designs. We have applied several importance sampling techniques—stratification, forced detection, and weight control through Russian roulette and splitting—to increase the computational efficiency of the Monte Carlo method 10‐ to 300‐fold. A description of these techniques, their validation, and sample performance results are given. Application of importance sampling methods makes it practical to study photon scattering in heterogeneous attenuators on workstations and minicomputers.

The use of importance sampling techniques to improve the efficiency of photon tracking in emission tomography simulations

The basic performance of the University of Washington modified Scanditronix SP3000 time-of-flight positron-emission tomograph (PET) has been characterized. Parameters measured include spatial resolution (in-plane and axial), count rate, sensitivity, scatter fraction, and recovery coefficient. Image examples include the Hoffman phantom and F-18 fluoride studies. >

Performance measurements of the SP3000/UW time-of-flight positron emission tomograph

Preliminary results of an assessment of the effects of changing the axial field of view (AFOV) and detector ring diameter (DRD) of a cylindrical PET tomograph on count rate performance are presented. The assessment was made using Monte Carlo simulations of an anthropomorphic phantom based on the Zubal phantom. This phantom was modified to include cylinders approximating arms and legs, and was sequentially stepped through the AFOV to simulate a whole-body scan covering an axial region of interest of 1 m. DRD was varied from /spl sim/60 cm to /spl sim/108 cm, and AFOV was varied from 10 cm to 60 cm. A simple activity distribution and dead time model was assumed to allow the calculation of noise-equivalent count (NEC) rates for a situation similar to that of a typical 18F-FDG study. Both the scatter fraction and singles flux were found to be strongly dependent on DRD, but only weakly dependent on AFOV when the latter was greater than /spl sim/25 cm. Trues and randoms sensitivity were strongly dependent on AFOV, and randoms sensitivity was also strongly dependent on DRD. Scatter and singles flux do not appear to be limiting factors for extended AFOV configurations, and randoms rates, while high, appear to be manageable with existing detector technology. This initial assessment suggests that for whole-body applications, substantial gains in NEC may be possible by extending the AFOV.

Robert L. Harrison

Papers

Introduction To Monte Carlo Simulation.

Preliminary Experience With The Photon History Generator Module Of A Public-domain Simulation System For Emission Tomography

The use of importance sampling techniques to improve the efficiency of photon tracking in emission tomography simulations

Performance measurements of the SP3000/UW time-of-flight positron emission tomograph

The effect of camera geometry on singles flux, scatter fraction and trues and randoms sensitivity for cylindrical 3D PET-a simulation study