Roger Lecomte

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.

Properties of LYSO and recent LSO scintillators for phoswich PET detectors

The luminescence and nuclear spectroscopic properties of the new cerium-doped rare-earth scintillator lutetium-yttrium oxyorthosilicate (Lu/sub 0.6/Y/sub 1.4/Si/sub 0.5/:Ce, LYSO) were investigated and compared to those of both recent and older LSO crystals. UV-excited luminescent spectra outline important similarities between LYSO and LSO scintillators. The two distinct Ce1 and Ce2 luminescence mechanisms previously identified in LSO are also present in LYSO scintillators. The energy and timing resolutions were measured using avalanche photodiode (APD) and photomultiplier tube (PMT) readouts. The dependence of energy resolution on gamma-ray energy was also assessed to unveil the crystal intrinsic resolution parameters. In spite of significant progress in light output and luminescence properties, the energy resolution of these scintillators appears to still suffer from an excess variance in the number of scintillation photons. Pulse-shape discrimination between LYSO and LSO scintillators has been successfully achieved in phoswich assemblies, confirming LYSO, with a sufficient amount of yttrium to modify the decay time, to be a potential candidate for depth-of-interaction determination in multicrystal PET detectors.

Investigation of depth-of-interaction by pulse shape discrimination in multicrystal detectors read out by avalanche photodiodes

The measurement of depth of interaction (DOI) within detectors is necessary to improve resolution uniformity across the FOV of small diameter PET scanners. DOI encoding by pulse shape discrimination (PSD) has definite advantages as it requires only one readout per pixel and it allows DOI measurement of photoelectric and Compton events. The PSD time characteristics of various scintillators were studied with avalanche photodiodes (APD) and the identification capability was tested in multi-crystal assemblies with up to four scintillators. In the PSD time spectrum of an APD-GSO/LSO/BGO/CsI(Tl) assembly, four distinct time peaks at 45, 26, 88 and 150 ns relative to a fast test pulse, having resolution of 10.6, 5.2, 20 and 27 ns, can be easily separated. Whereas the number and position of scintillators in the multi-crystal assemblies affect detector performance, the ability to identify crystals is not compromised. Compton events have a significant effect on PSD accuracy, suggesting that photopeak energy gating should be used for better crystal identification. However, more sophisticated PSD techniques using parametric time-energy histograms can also improve crystal identification in cases where PSD time or energy discrimination alone is inadequate. These results confirm the feasibility of PSD DOI encoding with APD-based detectors for PET.

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.

NEMA NU 4-2008 Comparison of Preclinical PET Imaging Systems

The National Electrical Manufacturers Association (NEMA) standard NU 4-2008 for performance measurements of small-animal tomographs was recently published. Before this standard, there were no standard testing procedures for preclinical PET systems, and manufacturers could not provide clear specifications similar to those available for clinical systems under NEMA NU 2-1994 and 2-2001. Consequently, performance evaluation papers used methods that were modified ad hoc from the clinical PET NEMA standard, thus making comparisons between systems difficult. Methods: We acquired NEMA NU 4-2008 performance data for a collection of commercial animal PET systems manufactured since 2000: microPET P4, microPET R4, microPET Focus 120, microPET Focus 220, Inveon, ClearPET, Mosaic HP, Argus (formerly eXplore Vista), VrPET, LabPET 8, and LabPET 12. The data included spatial resolution, counting-rate performance, scatter fraction, sensitivity, and image quality and were acquired using settings for routine PET. Results: The data showed a steady improvement in system performance for newer systems as compared with first-generation systems, with notable improvements in spatial resolution and sensitivity. Conclusion: Variation in system design makes direct comparisons between systems from different vendors difficult. When considering the results from NEMA testing, one must also consider the suitability of the PET system for the specific imaging task at hand.

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.

In vivo measurement of energy substrate contribution to cold-induced brown adipose tissue thermogenesis

The present study was designed to investigate the effects of cold on brown adipose tissue (BAT) energy substrate utilization in vivo using the positron emission tomography tracers [18F]fluorodeoxyglucose (glucose uptake), 14(R,S)‐[18F]fluoro‐6‐thiaheptadecanoic acid [nonesterified fatty acid (NEFA) uptake], and [11C]acetate (oxidative activity). The measurements were performed in rats adapted to 27°C, which were acutely subjected to cold (10°C) for 2 and 6 hours, and in rats chronically adapted to 10°C for 21 days, which were returned to 27°C for 2 and 6 hours. Cold exposure (acutely and chronically) led to increases in BAT oxidative activity, which was accompanied by concomitant increases in glucose and NEFA uptake. The increases were particularly high in cold‐adapted rats and largely readily reduced by the return to a warm environment. The cold‐induced increase in oxidative activity was meaningfully blunted by nicotinic acid, a lipolysis inhibitor, which emphasizes in vivo the key role of intracellular lipid in BAT thermogenesis. The changes in BAT oxidative activity and glucose and NEFA uptakes were paralleled by inductions of genes involved in not only oxidative metabolism but also in energy substrate replenishment (triglyceride and glycogen synthesis). The capacity of BAT for energy substrate replenishment is remarkable.—Labbé, S. M., Caron, A., Bakan, I., Laplante, M., Carpentier, A. C., Lecomte, R., Richard, D. In vivo measurement of energy substrate contribution to cold‐induced brown adipose tissue thermogenesis. FASEB J. 29, 2046‐2058 (2015). www.fasebj.org

Geometry Study of a High Resolution PET Detection System Using Small Detectors

The current trend in positron emission tomography (PET) towards very high spatial resolution tomographs raises the problem of detecting high energy gamma-rays with a high spatial accuracy while preserving the overall sensitivity of the camera. It is the purpose of this paper to investigate the effects of some geometrical parameters on the detection efficiency and intrinsic spatial resolution of a circular array of narrow closely packed detectors. Two approaches were employed: the first one uses the Monte-Carlo technique to simulate the interactions of gamma-rays in the detectors; the second one is based on the linear attenuation on a beam of gamma-rays impinging on a detector array. Aperture functions and modulation transfer functions were obtained for various configurations of the detectors and septas. Expressions for the resolution and the spectral signal-to-noise ratio were derived. It is shown that minor modifications to the geometry can improve both the efficiency and intrinsic resolution of the detector array.

Abnormal in vivo myocardial energy substrate uptake in diet-induced type 2 diabetic cardiomyopathy in rats

The purpose of this study was to determine in vivo myocardial energy metabolism and function in a nutritional model of type 2 diabetes. Wistar rats rendered insulin-resistant and mildly hyperglycemic, hyperinsulinemic, and hypertriglyceridemic with a high-fructose/high-fat diet over a 6-wk period with injection of a small dose of streptozotocin (HFHFS) and control rats were studied using micro-PET (microPET) without or with a euglycemic hyperinsulinemic clamp. During glucose clamp, myocardial metabolic rate of glucose measured with [(18)F]fluorodeoxyglucose ([(18)F]FDG) was reduced by approximately 81% (P < 0.05), whereas myocardial plasma nonesterified fatty acid (NEFA) uptake as determined by [(18)F]fluorothia-6-heptadecanoic acid ([(18)F]FTHA) was not significantly changed in HFHFS vs. control rats. Myocardial oxidative metabolism as assessed by [(11)C]acetate and myocardial perfusion index as assessed by [(13)N]ammonia were similar in both groups, whereas left ventricular ejection fraction as assessed by microPET was reduced by 26% in HFHFS rats (P < 0.05). Without glucose clamp, NEFA uptake was approximately 40% lower in HFHFS rats (P < 0.05). However, myocardial uptake of [(18)F]FTHA administered by gastric gavage was significantly higher in HFHFS rats (P < 0.05). These abnormalities were associated with reduced Glut4 mRNA expression and increased Cd36 mRNA expression and mitochondrial carnitine palmitoyltransferase 1 activity (P < 0.05). HFHFS rats display type 2 diabetes complicated by left ventricular contractile dysfunction with profound reduction in myocardial glucose utilization, activation of fatty acid metabolic pathways, and preserved myocardial oxidative metabolism, suggesting reduced myocardial metabolic efficiency. In this model, increased myocardial fatty acid exposure likely occurs from circulating triglyceride, but not from circulating plasma NEFA.