Architecture and Implementation of OpenPET Firmware and Embedded Software.

OpenPET is an open source, modular, extendible, and high-performance platform suitable for multi-channel data acquisition and analysis. Due to the flexibility of the hardware, firmware, and software architectures, the platform is capable of interfacing with a wide variety of detector modules not only in medical imaging but also in homeland security applications. Analog signals from radiation detectors share similar characteristics - a pulse whose area is proportional to the deposited energy and whose leading edge is used to extract a timing signal. As a result, a generic design method of the platform is adopted for the hardware, firmware, and software architectures and implementations. The analog front-end is hosted on a module called a Detector Board, where each board can filter, combine, timestamp, and process multiple channels independently. The processed data is formatted and sent through a backplane bus to a module called Support Board, where 1 Support Board can host up to eight Detector Board modules. The data in the Support Board, coming from 8 Detector Board modules, can be aggregated or correlated (if needed) depending on the algorithm implemented or runtime mode selected. It is then sent out to a computer workstation for further processing. The number of channels (detector modules), to be processed, mandates the overall OpenPET System Configuration, which is designed to handle up to 1,024 channels using 16-channel Detector Boards in the Standard System Configuration and 16,384 channels using 32-channel Detector Boards in the Large System Configuration.

Monitoring Tc dynamics in a bioreduced sediment: an investigation with gamma camera imaging of (99m)Tc-pertechnetate and (99m)Tc-DTPA.

We demonstrate the utility of nuclear medical imaging technologies and a readily available radiotracer, [(99m)Tc]TcO(4)(-), for the noninvasive monitoring of Fe(II) production in acetate-stimulated sediments from Old Rifle, CO, USA. Microcosms consisting of sediment in artificial groundwater media amended with acetate were probed by repeated injection of radiotracer over three weeks. Gamma camera imaging was used to noninvasively quantify the rate and extent of [(99m)Tc]TcO(4)(-) partitioning from solution to sediment. Aqueous Fe(II) and sediment-associated Fe(II) were also measured and correlated with the observed tracer behavior. For each injection of tracer, curves of (99m)Tc concentration in solution vs time were fitted to an analytic function that accounts for both the observed rate of sedimentation as well as the rate of (99m)Tc association with the sediment. The rate and extent of (99m)Tc association with the biostimulated sediment correlated well with the production of Fe(II), and a mechanism of [(99m)Tc]TcO(4)(-) reduction via reaction with surface-bound Fe(II) to form an immobile Tc(IV) species was inferred. After three weeks of bioreduction, a subset of microcosms was aerated in order to reoxidize the Fe(II) to Fe(III), which also destroyed the affinity of the [(99m)Tc]TcO(4)(-) for the sediments. However, within 3 days postoxidation, the rate of Tc(VII) reduction was faster than immediately before oxidation implying a rapid return to more extensive bioreduction. Furthermore, aeration soon after a tracer injection showed that sediment-bound Tc(IV) is rapidly resolubilized to Tc(VII). In contrast to the [(99m)Tc]TcO(4)(-), a second commercially available tracer, (99m)Tc-DTPA (diethylenetriaminepentaacetic acid), had minimal association with sediment in both controls and biostimulated sediments. These experiments show the promise of [(99m)Tc]TcO(4)(-) and (99m)Tc-DTPA as noninvasive imaging probes for a redox-sensitive radiotracer and a conservative flow tracer, respectively.

Imaging and modeling of flow in porous media using clinical nuclear emission tomography systems and computational fluid dynamics.

This paper presents experimental and modeling aspects of applying nuclear emission tomography to study fluid flow in laboratory packed porous media columns of the type frequently used in geophysics, geochemistry and hydrology research. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are used as non-invasive tools to obtain dynamic 3D images of radioactive tracer concentrations. Dynamic sequences obtained using 18F-FDG PET are used to trace flow through a 5 cm diameter × 20 cm tall sand packed column with and without an impermeable obstacle. In addition, a custom-made rotating column setup placed in a clinical two-headed SPECT camera is used to image 99mTc-DTPA tracer propagation in a through-flowing column (10 cm diameter × 30 cm tall) packed with recovered aquifer sediments. A computational fluid dynamics software package FLUENT is used to model the observed flow dynamics. Tracer distributions obtained in the simulations in the smaller column uniformly packed with sand and in the column with an obstacle are remarkably similar to the reconstructed images in the PET experiments. SPECT results demonstrate strongly non-uniform flow patterns for the larger column slurry-packed with sub-surface sediment and slow upward flow. In the numerical simulation of the SPECT study, two symmetric channels with increased permeability are prescribed along the column walls, which result in the emergence of two well-defined preferential flow paths. Methods and results of this work provide new opportunities in hydrologic and biogeochemical research. The primary target application for developed technologies is non-destructive, non-perturbing, quantitative imaging of flow dynamics within laboratory scale porous media systems.

Potentials of Digitally Sampling Scintillation Pulses in Timing Determination in PET.

We investigate the potentials of digitally sampling scintillation pulses techniques for positron emission tomography (PET) in this paper, focusing on the determination of the event time. We have built, and continue building, a digital library of PET event waveforms generated with various combinations of photo-detectors and scintillator materials, with various crystal sizes. Events in this digital library are obtained at a high sampling of 20 GSps (Giga-samples per second) so that their waveforms are recorded with high accuracy. To explore the potential advantages of digitally sampling scintillation pulses, we employ a dataset in the above-mentioned library to evaluate two methods for digitizing the event pulses and linear interpolation techniques to analyze the resulting digital samples. Our results show that the two digitization methods that we studied can yield a coincidence timing resolution of about 300 ps FWHM when applied to events generated by a pair of LSO + PMT detector units. This timing resolution is comparable with that is achieved by the same detector pair with a constant fraction discriminator (CFD). As a benchmark, regular-time sampling (RTS) method, usually implemented with very fast traditional analog-to-digital converters (ADCs) for digitizing scintillation pulses, is not feasible for a multi-channel system like a PET system. Digitizing scintillation pulses with multi-voltage threshold (MVT) method could be implemented at a reasonable cost for a PET system. With digitized PET event samples, various digital signal processing (DSP) techniques can be implemented to determine event arrival time. Our results have therefore demonstrated the promising potentials of digitally sampling scintillation pulses techniques in PET imaging.

Total-Body PET: Maximizing Sensitivity to Create New Opportunities for Clinical Research and Patient Care.

PET is widely considered the most sensitive technique available for noninvasively studying physiology, metabolism, and molecular pathways in the living human being. However, the utility of PET, being a photon-deficient modality, remains constrained by factors including low signal-to-noise ratio, long imaging times, and concerns about radiation dose. Two developments offer the potential to dramatically increase the effective sensitivity of PET. First by increasing the geometric coverage to encompass the entire body, sensitivity can be increased by a factor of about 40 for total-body imaging or a factor of about 4-5 for imaging a single organ such as the brain or heart. The world's first total-body PET/CT scanner is currently under construction to demonstrate how this step change in sensitivity affects the way PET is used both in clinical research and in patient care. Second, there is the future prospect of significant improvements in timing resolution that could lead to further effective sensitivity gains. When combined with total-body PET, this could produce overall sensitivity gains of more than 2 orders of magnitude compared with existing state-of-the-art systems. In this article, we discuss the benefits of increasing body coverage, describe our efforts to develop a first-generation total-body PET/CT scanner, discuss selected application areas for total-body PET, and project the impact of further improvements in time-of-flight PET.

Lesion detection and quantification performance of the Tachyon-I time-of-flight PET scanner: phantom and human studies.

The first generation Tachyon PET (Tachyon-I) is a demonstration single-ring PET scanner that reaches a coincidence timing resolution of 314 ps using LSO scintillator crystals coupled to conventional photomultiplier tubes. The objective of this study was to quantify the improvement in both lesion detection and quantification performance resulting from the improved time-of-flight (TOF) capability of the Tachyon-I scanner. We developed a quantitative TOF image reconstruction method for the Tachyon-I and evaluated its TOF gain for lesion detection and quantification. Scans of either a standard NEMA torso phantom or healthy volunteers were used as the normal background data. Separately scanned point source and sphere data were superimposed onto the phantom or human data after accounting for the object attenuation. We used the bootstrap method to generate multiple independent noisy datasets with and without a lesion present. The signal-to-noise ratio (SNR) of a channelized hotelling observer (CHO) was calculated for each lesion size and location combination to evaluate the lesion detection performance. The bias versus standard deviation trade-off of each lesion uptake was also calculated to evaluate the quantification performance. The resulting CHO-SNR measurements showed improved performance in lesion detection with better timing resolution. The detection performance was also dependent on the lesion size and location, in addition to the background object size and shape. The results of bias versus noise trade-off showed that the noise (standard deviation) reduction ratio was about 1.1-1.3 over the TOF 500 ps and 1.5-1.9 over the non-TOF modes, similar to the SNR gains for lesion detection. In conclusion, this Tachyon-I PET study demonstrated the benefit of improved time-of-flight capability on lesion detection and ROI quantification for both phantom and human subjects.

Total-body imaging: Transforming the role of positron emission tomography.

The first total-body positron emission tomography (TB-PET) scanner represents a radical change for experimental medicine and diagnostic health care.

A retrospective on the LBNL PEM project.

We present a retrospective on the LBNL Positron Emission Mammography (PEM) project, looking back on our design and experiences. The LBNL PEM camera utilizes detector modules that are capable of measuring depth of interaction (DOI) and places them into 4 detector banks in a rectangular geometry. In order to build this camera, we had to develop the DOI detector module, LSO etching, Lumirror-epoxy reflector for the LSO array (to achieve optimal DOI), photodiode array, custom IC, rigid-flex readout board, packaging, DOI calibration and reconstruction algorithms for the rectangular camera geometry. We will discuss the high-lights (good and bad) of these developments.

Monte Carlo calculations of PET coincidence timing: single and double-ended readout.

We present Monte Carlo computational methods for estimating the coincidence resolving time (CRT) of scintillator detector pairs in positron emission tomography (PET) and present results for Lu2SiO5 : Ce (LSO), LaBr3 : Ce, and a hypothetical ultra-fast scintillator with a 1 ns decay time. The calculations were applied to both single-ended and double-ended photodetector readout with constant-fraction triggering. They explicitly include (1) the intrinsic scintillator properties (luminosity, rise time, decay time, and index of refraction), (2) the exponentially distributed depths of interaction, (3) the optical photon transport efficiency, delay, and time dispersion, (4) the photodetector properties (fill factor, quantum efficiency, transit time jitter, and single electron response), and (5) the determination of the constant fraction trigger level that minimizes the CRT. The calculations for single-ended readout include the delayed photons from the opposite reflective surface. The calculations for double-ended readout include (1) the simple average of the two photodetector trigger times, (2) more accurate estimators of the annihilation photon entrance time using the pulse height ratio to estimate the depth of interaction and correct for annihilation photon, optical photon, and trigger delays, and (3) the statistical lower bound for interactions at the center of the crystal. For time-of-flight (TOF) PET we combine stopping power and TOF information in a figure of merit equal to the sensitivity gain relative to whole-body non-TOF PET using LSO. For LSO crystals 3 mm × 3 mm × 30 mm, a decay time of 37 ns, a total photoelectron count of 4000, and a photodetector with 0.2 ns full-width at half-maximum (fwhm) timing jitter, single-ended readout has a CRT of 0.16 ns fwhm and double-ended readout has a CRT of 0.111 ns fwhm. For LaBr3 : Ce crystals 3 mm × 3 mm × 30 mm, a rise time of 0.2 ns, a decay time of 18 ns, and a total of 7600 photoelectrons the CRT numbers are 0.14 ns and 0.072 ns fwhm, respectively. For a hypothetical ultra-fast scintillator 3 mm × 3 mm × 30 mm, a decay time of 1 ns, and a total of 4000 photoelectrons, the CRT numbers are 0.070 and 0.020 ns fwhm, respectively. Over a range of examples, values for double-ended readout are about 10% larger than the statistical lower bound.

A fast method for optical simulation of flood maps of light-sharing detector modules.

Optical simulation of the detector module level is highly desired for Position Emission Tomography (PET) system design. Commonly used simulation toolkits such as GATE are not efficient in the optical simulation of detector modules with complicated light-sharing configurations, where a vast amount of photons need to be tracked. We present a fast approach based on a simplified specular reflectance model and a structured light-tracking algorithm to speed up the photon tracking in detector modules constructed with polished finish and specular reflector materials. We simulated conventional block detector designs with different slotted light guide patterns using the new approach and compared the outcomes with those from GATE simulations. While the two approaches generated comparable flood maps, the new approach was more than 200-600 times faster. The new approach has also been validated by constructing a prototype detector and comparing the simulated flood map with the experimental flood map. The experimental flood map has nearly uniformly distributed spots similar to those in the simulated flood map. In conclusion, the new approach provides a fast and reliable simulation tool for assisting in the development of light-sharing-based detector modules with a polished surface finish and using specular reflector materials.

Preliminary performance characterization of DbPET2.1, a PET scanner dedicated to the imaging of the breast and extremities.

The combined effort of several laboratories at our institution resulted in the building of the first high resolution PET/CT prototype dedicated to imaging the body extremities. Ongoing clinical trials for breast cancer diagnosis and assessment of response to treatment underlined the need for a second generation prototype with improved electronics and spatial resolution. A preliminary version has been assembled and fully characterized. In this work we present further improvements in the detector performance as well as the readout electronics for the PET component. The detector consists of a 16×16 array of 1.27×1.27×20mm3 LYSO crystals, the smallest crystal size for completed breast PET prototypes to date, directly coupled to a position-sensitive photomultiplier tube (PSPMT). The scintillator crystals are polished on all 6 faces and separated by ~70 µm ESR reflector. The readout electronics were redesigned to reduce their footprint and improve timing resolution. We report a detector energy and timing resolution of 12% and 1.0 ns, respectively, and an average intrinsic spatial resolution of 1.29 mm (central row in one detector array). The new PET/CT has been fully assembled and initial system characterization is being perfomed. We report a system energy resolution of 15.7%, a timing resolution of 1.5 ns and an FBP image spatial resolution in the center of the FOV of 1.6 mm.

Fundamental limits of scintillation detector timing precision.

In this paper we review the primary factors that affect the timing precision of a scintillation detector. Monte Carlo calculations were performed to explore the dependence of the timing precision on the number of photoelectrons, the scintillator decay and rise times, the depth of interaction uncertainty, the time dispersion of the optical photons (modeled as an exponential decay), the photodetector rise time and transit time jitter, the leading-edge trigger level, and electronic noise. The Monte Carlo code was used to estimate the practical limits on the timing precision for an energy deposition of 511 keV in 3 mm × 3 mm × 30 mm Lu2SiO5:Ce and LaBr3:Ce crystals. The calculated timing precisions are consistent with the best experimental literature values. We then calculated the timing precision for 820 cases that sampled scintillator rise times from 0 to 1.0 ns, photon dispersion times from 0 to 0.2 ns, photodetector time jitters from 0 to 0.5 ns fwhm, and A from 10 to 10,000 photoelectrons per ns decay time. Since the timing precision R was found to depend on A(-1/2) more than any other factor, we tabulated the parameter B, where R = BA(-1/2). An empirical analytical formula was found that fit the tabulated values of B with an rms deviation of 2.2% of the value of B. The theoretical lower bound of the timing precision was calculated for the example of 0.5 ns rise time, 0.1 ns photon dispersion, and 0.2 ns fwhm photodetector time jitter. The lower bound was at most 15% lower than leading-edge timing discrimination for A from 10 to 10,000 photoelectrons ns(-1). A timing precision of 8 ps fwhm should be possible for an energy deposition of 511 keV using currently available photodetectors if a theoretically possible scintillator were developed that could produce 10,000 photoelectrons ns(-1).

Chemical stability of (99m)Tc-DTPA under aerobic and microbially mediated Fe(III)-reducing conditions in porous media.

(99m)Tc-DTPA has been used as a conservative tracer to quantify water transport through porous media. However, more information on the reactivity of this (99m)Tc compound under varying geochemical conditions is desirable to better understand its potential uses. We measured the speciation of Tc following amendment of (99m)Tc-DTPA to batch systems spanning a range of controlled biogeochemical conditions. Our results suggest that (99m)Tc-DTPA is stable under the reducing conditions tested. However, freshly precipitated Al-ferrihydrite may displace Tc(IV) from DTPA in the absence of Fe(III)-reducing conditions.

Optimal whole-body PET scanner configurations for different volumes of LSO scintillator: a simulation study.

The axial field of view (AFOV) of the current generation of clinical whole-body PET scanners range from 15-22 cm, which limits sensitivity and renders applications such as whole-body dynamic imaging or imaging of very low activities in whole-body cellular tracking studies, almost impossible. Generally, extending the AFOV significantly increases the sensitivity and count-rate performance. However, extending the AFOV while maintaining detector thickness has significant cost implications. In addition, random coincidences, detector dead time, and object attenuation may reduce scanner performance as the AFOV increases. In this paper, we use Monte Carlo simulations to find the optimal scanner geometry (i.e. AFOV, detector thickness and acceptance angle) based on count-rate performance for a range of scintillator volumes ranging from 10 to 93 l with detector thickness varying from 5 to 20 mm. We compare the results to the performance of a scanner based on the current Siemens Biograph mCT geometry and electronics. Our simulation models were developed based on individual components of the Siemens Biograph mCT and were validated against experimental data using the NEMA NU-2 2007 count-rate protocol. In the study, noise-equivalent count rate (NECR) was computed as a function of maximum ring difference (i.e. acceptance angle) and activity concentration using a 27 cm diameter, 200 cm uniformly filled cylindrical phantom for each scanner configuration. To reduce the effect of random coincidences, we implemented a variable coincidence time window based on the length of the lines of response, which increased NECR performance up to 10% compared to using a static coincidence time window for scanners with a large maximum ring difference values. For a given scintillator volume, the optimal configuration results in modest count-rate performance gains of up to 16% compared to the shortest AFOV scanner with the thickest detectors. However, the longest AFOV of approximately 2 m with 20 mm thick detectors resulted in performance gains of 25-31 times higher NECR relative to the current Siemens Biograph mCT scanner configuration.

Fundamental Limits of Spatial Resolution in PET.

The fundamental limits of spatial resolution in positron emission tomography (PET) have been understood for many years. The physical size of the detector element usually plays the dominant role in determining resolution, but the combined contributions from acollinearity, positron range, penetration into the detector ring, and decoding errors in the detector modules often combine to be of similar size. In addition, the sampling geometry and statistical noise further degrade the effective resolution. This paper describes quantitatively describes these effects, discusses potential methods for reducing the magnitude of these effects, and computes the ultimately achievable spatial resolution for clinical and pre-clinical PET cameras.

Detection performance analysis for time-of-flight PET.

In this paper, we investigate the performance of time-of-flight (TOF) positron emission tomography (PET) in improving lesion detectability. We present a theoretical approach to compare lesion detectability of TOF versus non-TOF systems and perform computer simulations to validate the theoretical prediction. A single-ring TOF PET tomograph is simulated using SimSET software, and images are reconstructed in 2D from list-mode data using a maximum a posteriori method. We use a channelized Hotelling observer to assess the detection performance. Both the receiver operating characteristic (ROC) and localization ROC curves are compared for the TOF and non-TOF PET systems. We first studied the SNR gains for TOF PET with different scatter and random fractions, system timing resolutions and object sizes. We found that the TOF information improves the lesion detectability and the improvement is greater with larger fractions of randoms, better timing resolution and bigger objects. The scatters by themselves have little impact on the SNR gain after correction. Since the true system timing resolution may not be known precisely in practice, we investigated the effect of mismatched timing kernels and showed that using a mismatched kernel during reconstruction always degrades the detection performance, no matter whether it is narrower or wider than the real value. Using the proposed theoretical framework, we also studied the effect of lumpy backgrounds on the detection performance. Our results indicated that with lumpy backgrounds, the TOF PET still outperforms the non-TOF PET, but the improvement is smaller compared with the uniform background case. More specifically, with the same correlation length, the SNR gain reduces with bigger number of lumpy patches and greater lumpy amplitudes. With the same variance, the SNR gain reaches the minimum when the width of the Gaussian lumps is close to the size of the tumor.

Photodetectors for Nuclear Medical Imaging.

There have been a number of recent advances in photodetector technology, notably in photomultiplier tubes with high quantum efficiency (up to ~50%), hybrid photodetectors, and silicon-based Geiger-mode photodetectors. This paper looks at the potential benefits that these technologies can bring to nuclear medicine, notably SPECT and PET. We find that while the potential benefits to SPECT are relatively small, they can bring performance improvements in many areas for PET.

DETECTION PERFORMANCE ANALYSIS FOR TIME-OF-FLIGHT PET.

In this paper, we investigate the performance of time-of-flight (TOF) PET in improving lesion detectability. We present a theoretical approach to compare lesion detectability of TOF versus non-TOF systems. Computer simulations are performed to validate the theoretical predictions. A TOF PET tomograph is simulated using the SimSET software. Images are reconstructed from list-mode data using a maximum a posteriori (MAP) method. We use a channelized Hotelling observer (CHO) to assess the detection performance. Both the receiver operating characteristic (ROC) and localization ROC (LROC) curves are compared for the TOF and non-TOF PET systems. We also study the SNR gains for TOF PET with different scatter and random fractions. Simulation results match with the theoretical predictions very well. Both results show that the TOF information improves lesion detectability and the improvement is greater with larger fractions of randoms and scatters.

Recent Advances and Future Advances in Time-of-Flight PET.

Simple theory predicts that the statistical noise variance in PET can be reduced by an order of magnitude by using time-of-flight (TOF) information. This reduction can be obtained by improving the coincidence timing resolution, and so would be achievable in clinical, whole body studies using with PET systems that differ little from existing cameras. The potential impact of this development is large, especially for oncology studies in large patients, where it is sorely needed. TOF PET was extensively studied in the 1980's but died away in the 1990's, as it was impossible to reliably achieve sufficient timing resolution without sacrificing other important PET performance aspects, such as spatial resolution and efficiency. Recent advances in technology (scintillators, photodetectors, and high speed electronics) have renewed interest in TOF PET, which is experiencing a rebirth. However, there is still much to be done, both in instrumentation development and evaluating the true benefits of TOF in modern clinical PET. This paper looks at what has been accomplished and what needs to be done before time-of-flight PET can reach its full potential.