Jules Cadorette

Initial results from the Sherbrooke avalanche photodiode positron tomograph

The design features and engineering constraints of a PET system based on avalanche photodiode (APD) detectors have been described in a previous report. Here, the authors present the initial results obtained with the Sherbrooke APD-PET scanner, a very high spatial resolution device designed for dynamic imaging of small and medium-sized laboratory animals such as rats, cats, rabbits and small monkeys. Its physical performance has been evaluated in terms of resolution, sensitivity, count rate, random and scatter fractions, contrast and relative activity recovery as a function of object size. The capabilities of the scanner for biomedical research applications have been demonstrated using phantom and animal studies.

Detector response models for statistical iterative image reconstruction in high resolution PET

One limitation in a practical implementation of statistical iterative image reconstruction is to compute a transition matrix accurately modeling the relationship between projection and image spaces. Detector response function (DRF) in positron emission tomography (PET) is broad and spatially-variant, leading to large transition matrices taking too much space to store. In this work, the authors investigate the effect of simpler DRF models on image quality in maximum likelihood expectation maximization reconstruction. The authors studied 6 cases of modeling projection/image relationship: tube/pixel geometric overlap with tubes centered on detector face; same as previous with tubes centered on DRF maximum; two different fixed-width Gaussian functions centered on DRF maximum weighing tube/pixel overlap; same as previous with a Gaussian of the same spectral resolution as DRF; analytic DRF based on linear attenuation of /spl gamma/-rays in detector arrays weighing tube/pixel overlap. The authors found that DRF oversimplification may affect visual image quality and image quantification dramatically, including artefact generation. They showed that analytic DRF yielded images of excellent quality for a small animal PET system with long, narrow detectors and generated a transition matrix for 2-D reconstruction that could be easily fitted into the memory of current stand-alone computers.

Performance Evaluation of the LabPET APD-Based Digital PET Scanner

The LabPETTM is a fully digital avalanche photodiode (APD) based PET scanner designed for state-of-the- art molecular and genomic imaging of small animals. Two versions of the scanner were evaluated, having 3.75 (LabPET4) and 7.5 cm axial FOV (LabPET8). The detectors are made of 2x2x10/12 mm3 LYSO and LGSO crystals assembled in phoswich pairs read out by an APD. After digital crystal identification, the average energy resolution is 24 plusmn 6% for LYSO and 25 plusmn 6% for LGSO. The scanner overall timing resolution is 6.6 ns for LYSO/LYSO and 10.7 ns for LGSO/LGSO coincidences after coarse timing alignment. The FBP reconstructed tangential/radial resolution is 1.3/1.4 mm FWHM (2.5/2.4 mm FWTM) at the FOV center and remains below 2.1 mm FWHM (3.6 mm FWTM) within the central 4-cm diameter FOV. MLEM reconstruction of a micro resolution phantom provided clear separation of the 1.35 mm spots and fair identification of 1 mm spots. With an energy window of 250-650 keV, the sensitivity is 1.1% for LabPET4 and 2.1% for LabPET8. The imaging capabilities of the scanner are demonstrated with in vivo images of rats and mice.

The Hardware and Signal Processing Architecture of LabPET™, a Small Animal APD-Based Digital PET Scanner

The highly multiplexed analog processing front-end of current Positron Emission Tomography (PET) scanners yields high accuracy for timing but adds significant dead time and offers little flexibility for improvement. A new fully digital APD-based scanner architecture is proposed wherein nuclear pulses are sampled directly at the output of the Charge Sensitive Preamplifier (CSP) with one free-running ADC per channel. This approach offers the opportunity to explore new digital signal processing algorithms borrowed from other fields like command and control theory, as well as advanced heuristics such as neural networks. The analog front-end consists of a dedicated 0.18- mum, 16-channel CMOS charge sensitive preamplifier. Digitization is performed with off-the-shelf dual 8-bit analog-to-digital converters running at 45-MSPS. Digital processing is shared between a FPGA and a Digital Signal Processor (DSP), which can process the data from up to 64 parallel channels without dead time. The FPGA deals with the initial signal analysis for energy measurement and time stamping, while crystal identification is deferred to the DSP running computation-intensive recursive algorithms. The entire system is controlled serially through a Firewire link by a Graphic User Interface. The initial LabPETtrade implementation of the system is a dedicated small animal scanner holding up to 4608 APD channels at an averaged count rate of up to 10 000 events/s each.

A New Tool for Molecular Imaging: The Microvolumetric β Blood Counter

Radiotracer kinetic modeling in small animals with PET allows absolute quantification of physiologic and biochemical processes in vivo. It requires blood and tissue tracer concentrations as a function of time. Manual sampling, the reference method for blood tracer concentration measurements, requires fairly large amounts of blood besides being technically difficult and time-consuming. An automated microvolumetric β blood counter (μBC) was designed to circumvent these limitations by measuring the blood activity in real time with PET scanning. Methods: The μBC uses direct β-particle detection to reduce its footprint and is entirely remote controlled for sampling protocol selection and real-time monitoring of measured parameters. Sensitivity has been determined for the most popular PET radioisotopes (18F, 13N, 11C, 64Cu). Dispersion within the sampling catheter has been modeled to enable automatic correction. Blood curves obtained with the μBC were compared with manual samples and PET-derived data. The μBC was used to estimate the myocardial blood flow (MBF) of mice injected with 13N-ammonia and to compare the myocardial metabolic rate of glucose (MMRG) of rats injected with 18F-FDG for arterial and venous cannulation sites. Results: The sensitivity limit ranges from 3 to 104 Bq/μL, depending on the isotope and the catheter used, and was found to be adequate for most small-animal studies. Automatic dispersion correction appears to be a good approximation of dispersion-free reference curves. Blood curves sampled with the μBC are well correlated with curves obtained from manual samples and PET images. With correction for dispersion, the MBF of anesthetized mice at rest was found to be 4.84 ± 0.5 mL/g/min, which is comparable to values found in the literature for rats. MMRG values derived from the venous blood tracer concentration are underestimated by 60% as compared with those derived from arterial blood. Conclusion: The μBC is a compact automated counter allowing real-time measurement of blood radioactivity for pharmacokinetic studies in animals as small as mice. Reliable and reproducible, the device makes it possible to increase the throughput of pharmacokinetic studies with reduced blood sample handling and staff exposure, contributing to speed up new drug development and evaluation.

High resolution positron emission tomography with a prototype camera based on solid state scintillation detectors

The prototype of a high-resolution PET (positron emission tomography) camera consisting of two opposite arrays of detectors with independent solid-state readout was built and tested. The basic detector unit is the RCA C30994 detector module consisting of two 3-mm*5-mm*20-mm BGO scintillators, each coupled to one silicon avalanche photodiode. The two-dimensional stacking capability of the module allows a high-resolution multiring detection system to be assembled without crystal coding. The prototype was used to simulate a 31-cm-diameter dual ring tomograph suitable for animal studies. Coincident detector pair resolution was measured, and the contributions to resolution loss were estimated using a platinum-sheathed 0.75 mm /sup 68/Ge line source. The intrinsic resolution is 1.9 mm FWHM (full width at half maximum), 3.5 mm FWTM at the center of the field. The reconstructed point spread function resolution in a stationary mode is 2.3 mm FWHM at the center and 3.1 mm FWHM (tangential), 3.9 mm FWHM (radial) 5 cm from the center. The axial resolution is less than 3.5 mm FWHM throughout the field. The ring sensitivity for an animal system is 67 kcps/mCi in air for an axial line source and 3.3 kcps/ mu Ci/ml for a 10-cm-diameter cylinder of /sup 22/Na solution. >

System Architecture of the LabPET Small Animal PET Scanner

To address modern molecular imaging requirements, a digital positron emission tomography (PET) scanner for small animals has been developed at Universite de Sherbrooke. Based on individual readout of avalanche photodiodes (APD) coupled to LYSO/LGSO phoswich detectors, the scanner supports up to 4608 channels in a 16.2 cm diameter, 11.25 cm axial field of view with an isotropic ~ 1.2 mm FWHM intrinsic spatial resolution at the center of the field of view. Custom data acquisition boards preprocess and sample APD signals at 45 MHz and compute in real time crystal identification, energy and timing information of detected events at an average sustained rate of up to 1250 raw counts per second per mm2 (10 000 cps/channel). Real time digital signal analysis also filters out events outside the pre-selected energy window with crystal granularity to eliminate Compton events and electronic noise. Retained events are then merged into a single stream through a real-time sorting tree, at which end prompt and delayed coincidences are extracted. A single Firewire link handles both control and data transfers with a host computer. The LabPET features four data recording modes, giving the user the choice to retain data for research or to minimize file size for high coincidence count rate and imaging purposes. The electronic system also supports time synchronized data insertion for flags such as vital signs used in gated image reconstruction. Aside from data acquisition, hardware can generate live energy and discrimination spectra suitable for fast, automatic channel calibration.

Architecture of a dual-modality, high-resolution, fully digital positron emission tomography/computed tomography (PET/CT) scanner for small animal imaging

Contemporary positron emission tomography (PET) scanners are commonly implemented with very large scale integration analog front-end electronics to reduce power consumption, space, noise, and cost. Analog processing yields excellent results in dedicated applications, but offers little flexibility for sophisticated signal processing or for more accurate measurements with newer, fast scintillation crystals. Design goals of the new Sherbrooke PET/computed tomography (CT) scanner are: 1) to achieve 1 mm resolution in both emission (PET) and transmission (CT) imaging using the same detector channels; 2) to be able to count and discriminate individual X-ray photons in CT mode. These requirements can be better met by sampling the analog signal from each individual detector channel as early as possible, using off-the-shelf, 8-b, 100-MHz, high-speed analog-to-digital converters (ADC) and digital processing in field programmable gate arrays (FPGAs). The core of the processing units consists of Xilinx SpartanIIe that can hold up to 16 individual channels. The initial architecture is designed for 1024 channels, but modularity allows extending the system up to 10 K channels or more. This parallel architecture supports count rates in excess of a million hits/s/scintillator in CT mode and up to 100 K events/s/scintillator in PET mode, with a coincidence time window of less than 10 ns full-width at half-maximum.

Time determination of BGO-APD detectors by digital signal processing for positron emission tomography

Coincidence timing resolution in Positron Emission Tomography (PET) can be improved by replacing fast analog pulse shaping and Constant Fraction Discriminator (CFD) with fully digital signal processing. This can be achieved by digitizing the signal from individual detectors using 100-MHz, 8-bit Analog-to-Digital converters (ADC) and by processing the data on-the-fly in Field Programmable Gate Arrays (FPGA). Various digital filters and baseline restorers were implemented and combined with numerical least mean square fit to the data to extract the time of interaction and the energy deposited in BGO-APD detectors. An intrinsic time resolution of 7.2 ns was obtained with digital techniques. However, it is shown that bias in the timestamp estimation can be introduced by digital time discrimination techniques, which could affect the ability of digital methods to accurately estimate random event rates by the delayed time window method. Accordingly, the coincidence FWHM metric should not be the only figure of merit when comparing digital and analog time discrimination strategies.

Energy dependence of scatter components in multispectral PET imaging

High resolution images in PET based on small individual detectors are obtained at the cost of low sensitivity and increased detector scatter. These limitations can be partially overcome by enlarging discrimination windows to include more low-energy events and by developing more efficient energy-dependent methods to correct for scatter radiation from all sources. The feasibility of multispectral scatter correction was assessed by decomposing response functions acquired in multiple energy windows into four basic components: object, collimator and detector scatter, and trues. The shape and intensity of these components are different and energy-dependent. They are shown to contribute to image formation in three ways: useful (true), potentially useful (detector scatter), and undesirable (object and collimator scatter) information to the image over the entire energy range. With the Sherbrooke animal PET system, restoration of detector scatter in every energy window would allow nearly 90% of all detected events to participate in image formation. These observations suggest that multispectral acquisition is a promising solution for increasing sensitivity in high resolution PET. This can be achieved without loss of image quality if energy-dependent methods are made available to preserve useful events as potentially useful events are restored and undesirable events removed.