David Prout

Detector concept for OPET-a combined PET and optical imaging system

The design of an imaging system capable of detecting both high-energy /spl gamma/-rays and optical wavelength photons is underway at the UCLA Crump Institute for Molecular Imaging. This system, which we call optical PET (OPET), will be capable of noninvasively and repeatedly imaging small animal models in vivo for the presence of PET and optical signals. In this study, we describe the physical principles behind the operation of the OPET imaging system and discuss the design concept for one of the detector modules. Additionally, we demonstrate the operation of an initial prototype detector module for simultaneous detection and imaging of annihilation radiation and single optical photons emanating from separate sources. These results indicate that the construction of an imaging system based on this detector technology is feasible.

Investigation of OPET performance using GATE, a Geant4-based Simulation software

A combined optical positron emission tomography (OPET) system is capable of both optical and PET imaging in the same setting and it can provide information/interpretation not possible in single mode imaging. The scintillator array here serves the dual function of coupling the optical signal from bioluminescence/fluorescence to the photodetector and also of channeling optical scintillations from the gamma rays. Here we report simulation results of the PET part of OPET using GATE, a Geant4 simulation package. The purpose of this investigation is the definition of the geometric parameters of the OPET tomograph. OPET is composed of six detector blocks arranged in a hexagonal ring shaped pattern with an inner radius of 15.4 mm. Each detector consists of a 2D array of 8/spl times/8 scintillator crystals each measuring 2/spl times/2/spl times/10 mm/sup 3/. Monte Carlo simulations were performed using the GATE software to measure absolute sensitivity, depth of interaction, and spatial resolution for two ring configurations, with and without gantry rotations, two crystal materials, and several crystal lengths. Images were reconstructed with filtered backprojection after angular interleaving and transverse 1D interpolation of the sinogram. We report absolute sensitivities nearly seven times that of the prototype microPET at the center of FOV and averages of 2.0 mm tangential and 2.3 mm radial resolutions with gantry rotations up to an 8.0 mm offset. These performance parameters indicate that the imaging spatial resolution and sensitivity of the OPET system will be suitable for high resolution and high sensitivity small animal PET imaging.

Readout of the optical PET, (OPET) detector

The design of an imaging system capable of detecting both high-energy /spl gamma/-rays and optical wavelength photons is underway at the Crump Institute for Molecular Imaging. This system will noninvasively image small animal models in vivo for the presence of positron emission tomographic (PET) and optical signals. The detector will consist of modules of multichannel photomultiplier tubes (MC-PMT) coupled to arrays of scintillator crystals. The MC-PMT will detect both the photons produced due to bioluminescence and the photons generated by the interaction of /spl gamma/-rays within the crystals. The long wavelength photons produced through bioluminescence are only slightly attenuated by these crystals and are detected directly at the photocathode of the MC-PMT, resulting in signals of small (5-10 mV) short (/spl sim/15 ns) pulses. In contrast, annihilation (511 keV) /spl gamma/-rays interacting in the scintillator crystal send large bursts of photons to the PMT, and result in pulses that can be as large as 500 mV and > 200 ns duration. The processing of pulses with such different characteristics in a single circuit requires significant alteration of the standard pulse processing circuitry used in PET scanners. In this paper, we discuss the requirements of such a circuit and show the results of implementation of one design using single and multiple channel PMTs.

MARS: a mouse atlas registration system based on a planar x-ray projector and an optical camera

This paper introduces a mouse atlas registration system (MARS), composed of a stationary top-view x-ray projector and a side-view optical camera, coupled to a mouse atlas registration algorithm. This system uses the x-ray and optical images to guide a fully automatic co-registration of a mouse atlas with each subject, in order to provide anatomical reference for small animal molecular imaging systems such as positron emission tomography (PET). To facilitate the registration, a statistical atlas that accounts for inter-subject anatomical variations was constructed based on 83 organ-labeled mouse micro-computed tomography (CT) images. The statistical shape model and conditional Gaussian model techniques were used to register the atlas with the x-ray image and optical photo. The accuracy of the atlas registration was evaluated by comparing the registered atlas with the organ-labeled micro-CT images of the test subjects. The results showed excellent registration accuracy of the whole-body region, and good accuracy for the brain, liver, heart, lungs and kidneys. In its implementation, the MARS was integrated with a preclinical PET scanner to deliver combined PET/MARS imaging, and to facilitate atlas-assisted analysis of the preclinical PET images.

Design and initial performance of PETbox4, a high sensitivity preclinical imaging tomograph

PETBox4, currently under development at the Crump Institute is a new tomograph dedicated to preclinical imaging of mice. This system presents a significant improvement on sensitivity and spatial resolution compared to the first generation PETBox. We report here on its design and initial performance characteristics.

A DOI Detector With Crystal Scatter Identification Capability for High Sensitivity and High Spatial Resolution PET Imaging

A new phoswich detector is being developed at the Crump Institute, aiming to provide improvements in sensitivity, and spatial resolution for PET. The detector configuration is comprised of two layers of pixelated scintillator crystal arrays, a glass lightguide and a light detector. The annihilation photon entrance (top) layer is a 48×48 array of 1.01 × 1.01 × 7 mm3 LYSO crystals. The bottom layer is a 32 × 32 array of 1.55 × 1.55 × 9 mm3 BGO crystals. A tapered, multiple-element glass lightguide is used to couple the exit end of the BGO crystal array (52 × 52 mm2) to the photosensitive area of the Position Sensitive Photomultiplier Tube (46 × 46 mm2), allowing the creation of flat panel detectors without gaps between the detector modules. Both simulations and measurements were performed to evaluate the characteristics and benefits of the proposed design. The GATE Monte Carlo simulation indicated that the total fraction of the cross layer crystal scatter (CLCS) events in singles detection mode for this detector geometry is 13.2%. The large majority of these CLCS events (10.1% out of 13.2%) deposit most of their energy in a scintillator layer other than the layer of first interaction. Identification of those CLCS events for rejection or correction may lead to improvements in data quality and imaging performance. Physical measurements with the prototype detector showed that the LYSO, BGO and CLCS events were successfully identified using the delayed charge integration (DCI) technique, with more than 95% of the LYSO and BGO crystal elements clearly resolved. The measured peak-to-valley ratios (PVR) in the flood histograms were 3.5 for LYSO and 2.0 for BGO. For LYSO, the energy resolution ranged from 9.7% to 37.0% full width at half maximum (FWHM), with a mean of 13.4 ± 4.8%. For BGO the energy resolution ranged from 16.0% to 33.9% FWHM, with a mean of 18.6 ± 3.2%. In conclusion, these results demonstrate that the proposed detector is feasible and can potentially lead to a high spatial resolution, high sensitivity and DOI PET system.

System Performance of OPET: A Combined Optical and PET Imaging System

OPET is an imaging system that detects both highenergy γ-rays and optical wavelength photons. This system is capable of non-invasively and repeatedly imaging small animal models in-vivo for the presence of γ-rays from PET tracers and optical signals from bioluminescence. OPET consists of six detector modules arranged to form a ring with a bore diameter of 3.5cm, where each module is made up of a 64-channel multichannel photomultiplier tube (PMT) coupled to an 8×8 BGO crystal array. The crystal lengths and widths are 2.15mm x 2.15mm respectively. The crystal heights vary along the face of the PMT such that the array presents a smooth curving profile. The front surface of the crystals is left open to allow optical wavelength photons to enter the detector module. A charge-division readout circuit is implemented to decode the signals from the 64 outputs of each PMT into four signals from which position information is obtained. These signals are amplified, shaped, and digitized, and finally processed using a field programmable gate array (FPGA). Flood images are used to obtain position look-up tables as well as pulse height spectra for each crystal in both PET and Optical mode operation. Basic system performance parameters have been measured for both operation modes of OPET including: sensitivity and count-rate performance. In PET mode the system has a sensitivity of 3.5% at the center of the field of view and an energy resolution around 36%. The sensitivity for optical wavelength photons was measured for each detector using a calibrated light source and varied from 0.6% to 2.0%. The maximum count rate in Optical mode is 106 cps per detector. The first dual-mode data acquisition of OPET was performed using a two chamber phantom. In one chamber was a set of six 0.8mm diameter rods filled with FDG, while the other chamber was filled with an enzyme and substrate used in bioluminescence studies of small animals. Images from both modes of operation are be presented.

A New Pulse Pileup Rejection Method Based on Position Shift Identification

Pulse pileup events degrade the signal-to-noise ratio (SNR) of nuclear medicine data. When such events occur in multiplexed detectors, they cause spatial misposition, energy spectrum distortion and degraded timing resolution, which leads to image artifacts. Pulse pileup is pronounced in PETbox4, a bench top PET scanner dedicated to high sensitivity and high resolution imaging of mice. In that system, the combination of high absolute sensitivity, long scintillator decay time (BGO) and highly multiplexed electronics lead to a significant fraction of pulse pileup, reached at lower total activity than for comparable instruments. In this manuscript, a new pulse pileup rejection method named position shift rejection (PSR) is introduced. The performance of PSR is compared with a conventional leading edge rejection (LER) method and with no pileup rejection implemented (NoPR). A comprehensive digital pulse library was developed for objective evaluation and optimization of the PSR and LER, in which pulse waveforms were directly recorded from real measurements exactly representing the signals to be processed. Physical measurements including singles event acquisition, peak system sensitivity and NEMA NU-4 image quality phantom were also performed in the PETbox4 system to validate and compare the different pulse pile-up rejection methods. The evaluation of both physical measurements and model pulse trains demonstrated that the new PSR performs more accurate pileup event identification and avoids erroneous rejection of valid events. For the PETbox4 system, this improvement leads to a significant recovery of sensitivity at low count rates, amounting to about 1/4th of the expected true coincidence events, compared to the LER method. Furthermore, with the implementation of PSR, optimal image quality can be achieved near the peak noise equivalent count rate (NECR).

A Digital Pulse Library for the Optimization of Signal Processing in PET

In this work, we developed a comprehensive digital pulse library as a reference data set, against which the performance of pulse processing algorithms can be evaluated. The pulses are directly recorded from real measurements with scintillation detectors multiplexed by a resistor divider network. This way, the pulses better represent systematic variations of detection sensitivity for detector panels due to differences in light sharing, light collection and crystal scatter among other effects. The pulse shapes exactly represent the signals to be processed in the data acquisition and signal processing unit, but for which the ground truth regarding energy, position and timing can be known. A conventional pulse pileup rejection method called leading edge rejection (LER) was evaluated with the help of the pulse library. The simulated pulse library based results show that the LER method can effectively suppress most of the pileup caused mispositioned events, while it also trades off against sensitivity loss. Physical measurements agree with the pulse library simulation results. In conclusion, the proposed evaluation method based on digital pulse library can significantly reduce the time and effort invested in the development and optimization of various signal processing algorithms.

Matched filter for event identification and processing in PET

Positron Emission Tomography (PET) is a technology that can image the spatial and temporal distribution of radio-labeled biomolecules in-vivo. It is dependent on the coincidence detection of photons emitted due to the annihilation of positrons. Most PET scanners use constant fraction discriminators (CFD) to confirm detector triggering. Following this, a blocking time window is used to allow processing of individual events. However, if a second (or more) event interacts with the detectors within this blocking time window, this method will not be capable to accurately identify its timing or energy, while the energy information for the first event is lost. Both energy and timing of all events are necessary for accurate event detection and localization. In these cases and without a method to identify individual events collected within the blocking time window, all events within the blocking window must be rejected, resulting in a real loss in sensitivity. The information loss in these situations is a significant problem when using high activity sources due to the high probability of event pile-up. To address this issue, we examined the performance of a matched filter when applied to raw pulses obtained from a pulse library derived from the PETBox system. Here, we compare the performance of the matched filter to CFD for event detection, positioning and timing. In addition, we show preliminary results from a real-time digital implementation of the matched filter on the PETBox FPGA. Preliminary results indicate that the matched filter can significantly improve the fidelity of the detection of true events at high count rates, as compared to conventional CFD, while event timing is somewhat compromised for the matched filter.