Performance of the Tachyon Time-of-Flight PET Camera.

We have constructed and characterized a time-of-flight Positron Emission Tomography (TOF PET) camera called the Tachyon. The Tachyon is a single-ring Lutetium Oxyorthosilicate (LSO) based camera designed to obtain significantly better timing resolution than the ~ 550 ps found in present commercial TOF cameras, in order to quantify the benefit of improved TOF resolution for clinically relevant tasks. The Tachyon's detector module is optimized for timing by coupling the 6.15 × 25 mm2 side of 6.15 × 6.15 × 25 mm3 LSO scintillator crystals onto a 1-inch diameter Hamamatsu R-9800 PMT with a super-bialkali photocathode. We characterized the camera according to the NEMA NU 2-2012 standard, measuring the energy resolution, timing resolution, spatial resolution, noise equivalent count rates and sensitivity. The Tachyon achieved a coincidence timing resolution of 314 ps +/- ps FWHM over all crystal-crystal combinations. Experiments were performed with the NEMA body phantom to assess the imaging performance improvement over non-TOF PET. The results show that at a matched contrast, incorporating 314 ps TOF reduces the standard deviation of the contrast by a factor of about 2.3.

A front-end readout Detector Board for the OpenPET electronics system.

We present a 16-channel front-end readout board for the OpenPET electronics system. A major task in developing a nuclear medical imaging system, such as a positron emission computed tomograph (PET) or a single-photon emission computed tomograph (SPECT), is the electronics system. While there are a wide variety of detector and camera design concepts, the relatively simple nature of the acquired data allows for a common set of electronics requirements that can be met by a flexible, scalable, and high-performance OpenPET electronics system. The analog signals from the different types of detectors used in medical imaging share similar characteristics, which allows for a common analog signal processing. The OpenPET electronics processes the analog signals with Detector Boards. Here we report on the development of a 16-channel Detector Board. Each signal is digitized by a continuously sampled analog-to-digital converter (ADC), which is processed by a field programmable gate array (FPGA) to extract pulse height information. A leading edge discriminator creates a timing edge that is "time stamped" by a time-to-digital converter (TDC) implemented inside the FPGA. This digital information from each channel is sent to an FPGA that services 16 analog channels, and then information from multiple channels is processed by this FPGA to perform logic for crystal lookup, DOI calculation, calibration, etc.

Artifacts in digital coincidence timing.

Digital methods are becoming increasingly popular for measuring time differences, and are the de facto standard in PET cameras. These methods usually include a master system clock and a (digital) arrival time estimate for each detector that is obtained by comparing the detector output signal to some reference portion of this clock (such as the rising edge). Time differences between detector signals are then obtained by subtracting the digitized estimates from a detector pair. A number of different methods can be used to generate the digitized arrival time of the detector output, such as sending a discriminator output into a time to digital converter (TDC) or digitizing the waveform and applying a more sophisticated algorithm to extract a timing estimator.All measurement methods are subject to error, and one generally wants to minimize these errors and so optimize the timing resolution. A common method for optimizing timing methods is to measure the coincidence timing resolution between two timing signals whose time difference should be constant (such as detecting gammas from positron annihilation) and selecting the method that minimizes the width of the distribution (i.e. the timing resolution). Unfortunately, a common form of error (a nonlinear transfer function) leads to artifacts that artificially narrow this resolution, which can lead to erroneous selection of the 'optimal' method. The purpose of this note is to demonstrate the origin of this artifact and suggest that caution should be used when optimizing time digitization systems solely on timing resolution minimization.

MODELING TIME DISPERSION DUE TO OPTICAL PATH LENGTH DIFFERENCES IN SCINTILLATION DETECTORS.

We characterize the nature of the time dispersion in scintillation detectors caused by path length differences of the scintillation photons as they travel from their generation point to the photodetector. Using Monte Carlo simulation, we find that the initial portion of the distribution (which is the only portion that affects the timing resolution) can usually be modeled by an exponential decay. The peak amplitude and decay time depend both on the geometry of the crystal, the position within the crystal that the scintillation light originates from, and the surface finish. In a rectangular parallelpiped LSO crystal with 3 mm × 3 mm cross section and polished surfaces, the decay time ranges from 10 ps (for interactions 1 mm from the photodetector) up to 80 ps (for interactions 50 mm from the photodetector). Over that same range of distances, the peak amplitude ranges from 100% (defined as the peak amplitude for interactions 1 mm from the photodetector) down to 4% for interactions 50 mm from the photodetector. Higher values for the decay time are obtained for rough surfaces, but the exact value depends on the simulation details. Estimates for the decay time and peak amplitude can be made for different cross section sizes via simple scaling arguments.

High-performance electronics for time-of-flight PET systems.

We have designed and built a high-performance readout electronics system for time-of-flight positron emission tomography (TOF PET) cameras. The electronics architecture is based on the electronics for a commercial whole-body PET camera (Siemens/CPS Cardinal electronics), modified to improve the timing performance. The fundamental contributions in the electronics that can limit the timing resolution include the constant fraction discriminator (CFD), which converts the analog electrical signal from the photo-detector to a digital signal whose leading edge is time-correlated with the input signal, and the time-to-digital converter (TDC), which provides a time stamp for the CFD output. Coincident events are identified by digitally comparing the values of the time stamps. In the Cardinal electronics, the front-end processing electronics are performed by an Analog subsection board, which has two application-specific integrated circuits (ASICs), each servicing a PET block detector module. The ASIC has a built-in CFD and TDC. We found that a significant degradation in the timing resolution comes from the ASIC's CFD and TDC. Therefore, we have designed and built an improved Analog subsection board that replaces the ASIC's CFD and TDC with a high-performance CFD (made with discrete components) and TDC (using the CERN high-performance TDC ASIC). The improved Analog subsection board is used in a custom single-ring LSO-based TOF PET camera. The electronics system achieves a timing resolution of 60 ps FWHM. Prototype TOF detector modules are read out with the electronics system and give coincidence timing resolutions of 259 ps FWHM and 156 ps FWHM for detector modules coupled to LSO and LaBr3 crystals respectively.

Real-time quantitative ex vivo direct autoradiography with 10 µm pixel resolution.

We present three new autoradiography methods to map positron emission rate of a bio-specimen slice with high resolution. One is based on LBNL scientific charge coupled device (CCD) and the other two are based on conventional CCDs. High conversion efficiency (100k e-h pairs / 0.5 MeV positron) and low dark current (1.75 × 10(-4) e-/pix/sec) can be achieved using the LBNL CCD. The theoretical calculations and preliminary experiments show that an 86 µm spatial resolution can be achieved when imaging a 100 µm thick tissue soaked with (18)F which produce higher energy positron. The main disadvantage of the LBNL CCD we tested is that a very low operating temperature is required to eliminate dark current. This dramatically increases the system cost. In addition, the integration time of the CCD needs to be short enough to avoid overlapping of the positron trajectories. Conventional CCDs have lower conversion efficiency (2k e-h pairs / 0.5 MeV positron) and higher dark current (200 e-/pix/sec), but are more cost-efficient and the requirement for the readout frequency is much lower. The conversion efficiency of the conventional CCD imager can be improved by 17 times by inserting a 100 µm layer of phosphor between the sample and the imager. However, the light emitted from the phosphor screen will be ~100 µm diameter, which severely degrades the spatial resolution. A high readout frequency is also required to avoid the overlapping. The CCD systems designed in this study will be used to map positron emission rate of bio-specimens such as cancerous tissues acquired in regular biopsy procedure. They can also be used to corroborate tracer kinetic modeling at a cellular level.

A Design of a PET Detector Using Micro-Channel Plate Photomultipliers with Transmission-Line Readout.

A computer simulation study has been conducted to investigate the feasibility of a positron emission tomography (PET) detector design by using micro-channel plate (MCP) photomultiplier tubes (PMT) with transmission-line (TL) read-out and waveform sampling. The detector unit consisted of a 24×24 array of pixelated LSO crystals, each of which was 4×4×25 mm(3) in size, and two 102×102 mm(2) MCP-PMTs coupled to both sides of the scintillator array. The crystal (and TL) pitch was 4.25 mm and reflective medium was inserted between the crystals. The transport of the optical photons inside the scintillator were simulated by using the Geant4 package. The output pulses of the MCP-PMT/TL unit were formed by applying the measured single photo-electron response of the MCP-PMT/TL unit to each individual photon that interacts with the photo-cathode of the MCP-PMT. The waveforms of the pulses at both ends of the TL strips were measured and analyzed to produce energy and timing information for the detected event. An experimental setup was developed by employing a Photonis Planacon MCP-PMT (XP85022) and a prototype TL board for measuring the single photo-electron response of the MCP-PMT/TL. The simulation was validated by comparing the predicted output pulses to measurements obtained with a single MCP-PMT/TL coupled to an LSO crystal exposed to 511 keV gamma rays. The validated simulation was then used to investigate the performance of the proposed new detector design. Our simulation result indicates an energy resolution of ~11% at 511 keV. When using a 400-600 keV energy window, we obtain a coincidence timing resolution of ~323 ps FWHM and a coincidence detection efficiency of ~40% for normally-incident 511keV photons. For the positioning accuracy, it is determined by the pitch of the TLs (and crystals) in the direction normal to the TLs and measured to be ~2.5 mm in the direction parallel to the TLs. The energy and timing obtained at the front- and back-end of the scintillator array also show differences that are correlated with the depth of interaction of the event.

Optimization of a LSO-Based Detector Module for Time-of-Flight PET.

We have explored methods for optimizing the timing resolution of an LSO-based detector module for a single-ring, "demonstration" time-of-flight PET camera. By maximizing the area that couples the scintillator to the PMT and minimizing the average path length that the scintillation photons travel, a single detector timing resolution of 218 ps fwhm is measured, which is considerably better than the ~385 ps fwhm obtained by commercial LSO or LYSO TOF detector modules. We explored different surface treatments (saw-cut, mechanically polished, and chemically etched) and reflector materials (Teflon tape, ESR, Lumirror, Melinex, white epoxy, and white paint), and found that for our geometry, a chemically etched surface had 5% better timing resolution than the saw-cut or mechanically polished surfaces, and while there was little dependence on the timing resolution between the various reflectors, white paint and white epoxy were a few percent better. Adding co-dopants to LSO shortened the decay time from 40 ns to ~30 ns but maintained the same or higher total light output. This increased the initial photoelectron rate and so improved the timing resolution by 15%. Using photomultiplier tubes with higher quantum efficiency (blue sensitivity index of 13.5 rather than 12) improved the timing resolution by an additional 5%. By choosing the optimum surface treatment (chemically etched), reflector (white paint), LSO composition (co-doped), and PMT (13.5 blue sensitivity index), the coincidence timing resolution of our detector module was reduced from 309 ps to 220 ps fwhm.

A Multi-Threshold Sampling Method for TOF PET Signal Processing.

As an approach to realizing all-digital data acquisition for positron emission tomography (PET), we have previously proposed and studied a multi-threshold sampling method to generate samples of a PET event waveform with respect to a few user-defined amplitudes. In this sampling scheme, one can extract both the energy and timing information for an event. In this paper, we report our prototype implementation of this sampling method and the performance results obtained with this prototype. The prototype consists of two multi-threshold discriminator boards and a time-to-digital converter (TDC) board. Each of the multi-threshold discriminator boards takes one input and provides up to 8 threshold levels, which can be defined by users, for sampling the input signal. The TDC board employs the CERN HPTDC chip that determines the digitized times of the leading and falling edges of the discriminator output pulses. We connect our prototype electronics to the outputs of two Hamamatsu R9800 photomultiplier tubes (PMTs) that are individually coupled to a 6.25×6.25×25mm(3) LSO crystal. By analyzing waveform samples generated by using four thresholds, we obtain a coincidence timing resolution of about 340 ps and an ∼18% energy resolution at 511 keV. We are also able to estimate the decay-time constant from the resulting samples and obtain a mean value of 44ns with an ∼9 ns FWHM. In comparison, using digitized waveforms obtained at a 20 GSps sampling rate for the same LSO/PMT modules we obtain ∼300 ps coincidence timing resolution, ∼14% energy resolution at 511 keV, and ∼5 ns FWHM for the estimated decay-time constant. Details of the results on the timing and energy resolutions by using the multi-threshold method indicate that it is a promising approach for implementing digital PET data acquisition.

OpenPET: A Flexible Electronics System for Radiotracer Imaging.

We present the design for OpenPET, an electronics readout system designed for prototype radiotracer imaging instruments. The critical requirements are that it has sufficient performance, channel count, channel density, and power consumption to service a complete camera, and yet be simple, flexible, and customizable enough to be used with almost any detector or camera design. An important feature of this system is that each analog input is processed independently. Each input can be configured to accept signals of either polarity as well as either differential or ground referenced signals. Each signal is digitized by a continuously sampled ADC, which is processed by an FPGA to extract pulse height information. A leading edge discriminator creates a timing edge that is "time stamped" by a TDC implemented inside the FPGA. This digital information from each channel is sent to an FPGA that services 16 analog channels, and information from multiple channels is processed by this FPGA to perform logic for crystal lookup, DOI calculation, calibration, etc. As all of this processing is controlled by firmware and software, it can be modified / customized easily. The system is open source, meaning that all technical data (specifications, schematics and board layout files, source code, and instructions) will be publicly available.

Effect of 176Lu background on singles transmission for LSO-based PET cameras.

We explore how the radioactive background from naturally occurring 176Lu affects single photon transmission imaging for lutetium orthosilicate (LSO) scintillator-based PET cameras by estimating the transmission noise equivalent count rate (NECR) including this background. Assuming a typical PET camera geometry (80 cm detector ring diameter), we use a combination of measurement and analytic computation to estimate the counting rates due to transmission, scatter and background events as a function of singles transmission source strength. We then compute a NECR for singles transmission. We find that the presence of radiation from the naturally occurring 176Lu reduces the NECR by 60% or higher for source strengths less than 10 mCi, and that a 25% reduction of the NECR can occur even with a source strength of 40 mCi.

List-mode maximum-likelihood reconstruction applied to positron emission mammography (PEM) with irregular sampling.

We present a preliminary study of list-mode likelihood reconstruction of images for a rectangular positron emission tomograph (PET) specifically designed to image the human breast. The prospective device consists of small arrays of scintillation crystals for which depth of interaction is estimated. Except in very rare instances, the number of annihilation events detected is expected to be far less than the number of distinguishable events. If one were to histogram the acquired data, most histogram bins would remain vacant. Therefore, it seems natural to investigate the efficacy of processing events one at a time rather than processing the data in histogram format. From a reconstruction perspective, the new tomograph presents a challenge in that the rectangular geometry leads to irregular radial and angular sampling, and the field of view extends completely to the detector faces. Simulations are presented that indicate that the proposed tomograph can detect 8-mm-diameter spherical tumors with a tumor-to-background tracer density ratio of 3:1 using realistic image acquisition parameters. Spherical tumors of 4-mm diameter are near the limit of detectability with the image acquisition parameters used. Expressions are presented to estimate the loss of image contrast due to Compton scattering.

Advances in positron tomography for oncology.

Development of PET instrumentation over the past 42 years has moved from simple dual-detector coincidence scanners, to proposed systems having 60,000 detectors and simultaneous coverage of 15-cm regions of the body with spatial resolutions better than 4 mm. The principal determinants of positron emission tomography (PET) instrumentation advances are positron range, noncollinearity of the annihilation photons, scattering, random event rates, detector size, efficiency, speed and light output; capability to correct for depth of crystal interaction, attenuation compensation, axial coverage, and rapid data analysis and presentation. While general-purpose systems with 2-mm resolution are expected, special-purpose PET devices are being built for breast and brain tumor studies with resolutions from 1.7 to 5 mm.