High-resolution Positron Emission Tomography System Research Articles

Development of a Novel [11C]CO-Labeled Positron Emission Tomography Radioligand [11C]BIO-1819578 for the Detection of O-GlcNAcase Enzyme Activity.

Imaging O-GlcNAcase OGA by positron emission tomography (PET) could provide information on the pathophysiological pathway of neurodegenerative diseases and important information on drug-target engagement and be helpful in dose selection of therapeutic drugs. Our aim was to develop an efficient synthetic method for labeling BIO-1819578 with carbon-11 using 11CO for evaluation of its potential to measure levels of OGA enzyme in non-human primate (NHP) brain using PET. Radiolabeling was achieved in one-pot via a carbon-11 carbonylation reaction using [11C]CO. The detailed regional brain distribution of [11C]BIO-1819578 binding was evaluated using PET measurements in NHPs. Brain radioactivity was measured for 93 min using a high-resolution PET system, and radiometabolites were measured in monkey plasma using gradient radio HPLC. Radiolabeling of [11C]BIO-1819578 was successfully accomplished, and the product was found to be stable at 1 h after formulation. [11C]BIO-1819578 was characterized in the cynomolgus monkey brain where a high brain uptake was found (7 SUV at 4 min). A pronounced pretreatment effect was found, indicating specific binding to OGA enzyme. Radiolabeling of [11C]BIO-1819578 with [11C]CO was successfully accomplished. [11C]BIO-1819578 binds specifically to OGA enzyme. The results suggest that [11C]BIO-1819578 is a potential radioligand for imaging and for measuring target engagement of OGA in the human brain.

Evaluation of a modular all-in-one high-resolution PET detector and readout electronics setup

Objective. The all-in-one solution and modularity of the C13500 series TOF-PET detector modules (Hamamatsu Photonics K.K., Hamamatsu, Japan) make them a highly attractive candidate for the development of positron emission tomography (PET) systems. However, the commercially available portfolio targets clinical whole-body PET systems with a scintillation crystal cross area of 3.1 × 3.1 mm2. To extend the modules for high resolution (preclinical or organ specific) systems, the support for smaller scintillation crystals is required. Approach. In this work, a PET detector was developed based on the TOF-PET modules using a light sharing approach, 16 × 16 lutetium oxyorthosilicate (LSO) scintillation crystals with a size of 1.51 × 1.51 × 10.00 mm3 readout with 8 × 8 photosensor channels of size 3.0 × 3.0 mm2. In addition to hardware and software development, the optimized parameter settings for the adapted configuration were evaluated. Main Results. A factor of two in amplification of the analog signal compared to the minimum gain setting was necessary for an accurate crystal identification (peak-to-valley ratio 14.9 ± 5.9). A further increase to a factor of three was not determined as optimum as the time over threshold duration, thus pile-up probability, increased from 1032.1 ± 109.5 to 1789.5 ± 218.5 ns (photopeak position). With this amplification a full width at half maximum (FWHM) energy resolution of 14.1 ± 2.0% and a high linearity of the energy detection was obtained. A FWHM coincidence resolving time (CRT) of 313 ps was achieved by using a low timing threshold, increasing the bandwidth of the front-end circuit and using a narrow ± 1σ energy window. To approximately double the sensitivity and reduce the power consumption, the timing parameters were adjusted resulting in a FWHM CRT of 354 ps (±2σ). Significance. Based on the results obtained with the proof-of-concept detector setup, we confirm the modularity and flexibility of the all-in-one TOF-PET detector modules for the future development of application-specific high-resolution PET systems.

Depth-of-interaction positron emission tomography detector with 45° tilted silicon photomultipliers using dual-ended signal readout.

Small-animal positron emission tomography (PET) systems are widely used in molecular imaging research and drug development. There is also growing interest in organ-dedicated clinical PET systems. In these small-diameter PET systems, the measurement of the depth-of-interaction (DOI) of annihilation photons in scintillation crystals allows for the correction of parallax error in PET system, leading to an improvement on the spatial resolution uniformity. The DOI information is also useful for improving the timing resolution of PET system as it enables the correction of DOI-dependent time walk in the arrival time difference measurement of annihilation photon pairs. The dual-ended readout scheme is one of the most widely investigated DOI measurement methods, which collects visible photons using a pair of photosensors located at both ends of the scintillation crystal. Although the dual-ended readout allows for simple and accurate DOI estimation, it requires twice the number of photosensors compared to the single-ended readout scheme. To effectively reduce the number of photosensors in a dual-ended readout scheme, we propose a novel PET detector configuration that employs 45° tilted and sparsely arranged silicon photomultipliers (SiPMs). In this configuration, the angle between the scintillation crystal and SiPM is 45°. Therefore, and thus, the diagonal of the scintillation crystal matches one of the lateral sides of the SiPM. Accordingly, it allows for the use of SiPM device larger than the scintillation crystal, thereby improving light collection efficiency with a higher fill factor and reducing SiPM quantity. In addition, all scintillation crystals can achieve more uniform performance than other dual-ended readout methods with a sparse SiPM arrangement because 50% of the scintillation crystal cross section is commonly in contact with the SiPM. To demonstrate the feasibility of our proposed concept, we implemented a PET detector that employs a 4 4 LSO block with a single crystal dimension of 3.03 × 3.03 × 20 mm3 and a 45° tilted SiPM array. The 45° tilted SiPM array consists of 2 × 3 SiPM elements at the top ("Top SiPM") and 3 × 2 SiPM elements at the bottom ("Bottom SiPM"). Each crystal element of the 4 × 4 LSO block is optically coupled with each quarter section of the Top SiPM and Bottom SiPM pair. To characterize the performance of the PET detector, the energy, DOI, and timing resolution were measured for all 16 crystals. The energy data was obtained by summing all the charges from the Top SiPMs and Bottom SiPMs, and the DOI resolution was measured by irradiating the side of the crystal block at five different depths (2, 6, 10, 14, and 18mm). The timing was estimated by averaging the arrival time of the annihilation photons measured at the Top SiPMs and Bottom SiPMs (Method 1). The DOI-dependent time-walk effect was further corrected by using DOI information and statistical variations in the trigger times at the Top SiPMs and Bottom SiPMs (Method 2). The average DOI resolution of the proposed PET detector was 2.5mm, thereby resolving the DOI at five different depths, and the average energy resolution was 16% full width at half maximum (FWHM). When Methods 1 and 2 were applied, the coincidence timing resolutions were 448 and 411ps FWHM, respectively. We expect that our novel low-cost PET detector design with 45° tilted SiPMs and a dual-ended readout scheme would be a suitable solution for constructing a high-resolution PET system with DOI encoding capability.

High-resolution monolithic LYSO detector with 6-layer depth-of-interaction for clinical PET

The system spatial resolution of whole-body positron emission tomography (PET) is limited to around 2 mm due to positron physics and the large diameter of the bore. To stay below this ‘physics’-limit a scintillation detector with an intrinsic spatial resolution of around 1.3 mm is needed. Currently used detector technology consists of arrays of 2.6–5 mm segmented scintillator pixels which are the dominant factor contributing to the system resolution. Pixelated detectors using smaller pixels exist but face major drawbacks in sensitivity, timing, energy resolution and cost. Monolithic continuous detectors, where the spatial resolution is determined by the shape of the light distribution on the photodetector array, are a promising alternative. Without having the drawbacks of pixelated detectors, monolithic ones can also provide depth-of-interaction (DOI) information. In this work we present a monolithic detector design aiming to serve high-resolution clinical PET systems while maintaining high sensitivity. A 50 × 50 × 16 mm3 Lutetium–Yttrium oxyorthosilicate scintillation crystal with silicon photomultiplier (SiPM) backside readout is calibrated in singles mode by a collimated beam obtaining a reference dataset for the event positioning. A mean nearest neighbour (MNN) algorithm and an artificial neural network for positioning are compared. The targeted intrinsic detector resolution of 1.3 mm needed to reach a 2 mm resolution on system level was accomplished with both algorithms. The neural network achieved a mean spatial resolution of 1.14 mm FWHM for the whole detector and 1.02 mm in the centre (30 × 30 mm2). The MNN algorithm performed slightly worse with 1.17 mm for the whole detector and 1.13 mm in the centre. The intrinsic DOI information will also result in uniform system spatial resolution over the full field of view.

Penalized maximum-likelihood reconstruction for improving limited-angle artifacts in a dedicated head and neck PET system

Positron emission tomography (PET) suffers from limited spatial resolution in current head and neck cancer management. We are building a dual-panel high-resolution PET system to aid the detection of tumor involvement in small lymph nodes (10 mm in diameter). The system is based on cadmium zinc telluride (CZT) detectors with cross-strip electrode readout (1 mm anode pitch and 5 mm cathode pitch). One challenge of the dual-panel system is that the limited angular coverage of the imaging volume leads to artifacts in reconstructed images, such as the elongation of lesions. In this work, we leverage a penalized maximum-likelihood (PML) reconstruction for the limited-angle PET system. The dissimilarity between the image to be reconstructed and a prior image from a low-resolution whole-body scanner is penalized. An image-based resolution model is incorporated into the regularization. Computer simulations were used to evaluate the performance of the method. Results demonstrate that the elongation of the 6-mm and 8-mm diameter hot spheres is eliminated with the regularization strength γ being 0.02 or larger. The PML reconstruction yields higher contrast recovery coefficient (CRC) of hot spheres compared to the maximum-likelihood reconstruction, as well as the low-resolution whole-body image, across all hot sphere sizes tested (3, 4, 6, and 8 mm). The method studied in this work provides a way to mitigate the limited-angle artifacts in the reconstruction from limited-angle PET data, making the high-resolution dual-panel dedicated head and neck PET system promising for head and neck cancer management.

Experimental Approach to Evaluate the 11C Perfusion and Diffusion in Small Animal Tissues for HadronPET Applications.

The development of a reliable dose monitoring system in hadron therapy is essential in order to control the treatment plan delivery. Positron Emission Tomography (PET) is the only method used in clinics nowadays for quality assurance. However, the accuracy of this method is limited by the loss of signal due to the biological washout processes. Up to the moment, very few studies measured the washout processes and there is no database of washout data as a function of the tissue and radioisotope. One of the main difficulties is related to the complexity of such measurements, along with the limited time slots available in hadron therapy facilities. Thus, in this work, we proposed an alternative in vivo methodology for the measurement and modeling of the biological washout parameters without any radiative devices. It consists in the implementation of a point-like radioisotope source by direct injection on the tissues of interest and its measurement by means of high-resolution preclinical PET systems. In particular, the washout of 11C carbonate radioisotopes was assessed, considering that 11C is is the most abundant β+ emitter produced by carbon beams. 11C washout measurements were performed in several tissues of interest (brain, muscle and 9L tumor xenograf) in rodents (Wistar rat). Results show that the methodology presented is sensitive to the washout variations depending on the selected tissue. Finally, a first qualitative correlation between 11C tumor washout properties and tumor metabolism (via 18F-FDG tracer uptake) was found.

Feasibility Study on Silicon Photomultiplier With Epitaxial Quenching Resistors as the Readout for PET Detectors

The silicon photomultiplier (SiPM) with epitaxial quenching resistors (EQR) is a novel SiPM technology currently under research and development. It has distinguished features of simple device structure, high fill factor, high microcell density, large dynamic range, and fast recovery time. In this paper, we report its latest developments aiming at positron emission tomography (PET) applications. The EQR type SiPM with active area of $2.2~\hbox{mm} \times 2.2~\hbox{mm}$ demonstrated a peak PDE of 11.6% at 460 nm, PDE greater than 8.0% at 420 nm, temperature coefficient for breakdown voltage of 16 mV per $^\circ {\rm C}$ , with the fill factor of 40% and microcell density as high as $\sim 9000/\hbox{mm}^{2}$ . We measured a time resolution better than 357 ps FWHM and a 17.5% FWHM energy resolution at 511 keV by 1-to-1 coupling of the device with a $2~\hbox{mm} \times 2~\hbox{mm} \times 10~\hbox{mm}$ lutetium yttrium oxyorthosilicate (LYSO) crystal without any preamplifiers. Those preliminary results show the potential of using such SiPM to build a high spatial resolution and high timing resolution PET system.

Performance Characteristics of CZT Detectors for PET Imaging Applications

Positron emission tomography (PET) is a non-invasive, in-vivo, imaging technology that plays a critical role in cancer detection, as well as in molecular and cellular imaging. For PET imaging, and attractive alternative to a scintillator and photomultiplier assembly (PMT) is the Cadmium Zinc Telluride (CZT) detector. Th CZT and other detectors have recently attracted extensive research interests in the development of novel PET imaging systems [1, 2]. The benefits of CZT include relatively high atomic number, density, large band-gap energy, high spatial resolution through fine electrodes, and superior energy resolution for 511 keV photons due to direct charge carrier generation/collection rather than indirect process of scintillation photon emission as in the scintillator and PMT module. In addition, it has shown great promises to be used as a 3D positioning detector by incorporating depth-of-interaction (DOI) resolution of CZT, which can help mitigate parallax error in PET systems.In this work, we developed an analytical model to study the charge collection and temporal behavior, which is expected to assist to optimize a number of design parameters including anode/cathode electrode pitch, steering electrode pitch and voltage bias.Two common electrode configurations (pixilated and cross strip) for CZT detectors are shown in Fig. 1. When a 511 keV gamma ray hits the detector, a number of electron-holes are generated and travel within the internal electric field E. As stated by Shockley–Ramo theorem [3], the induced charge q(t) builds up as the electron-hole pairs moves from position r1 to r2, which can be written as q(t)=q0(Φω(r2)-Φω(r1))，where q0 is the elementary charge of electron, Φω is the weighting potential. To model the temporal dependency that impacts the time resolution, the drift time te,h of Δx distance is te,h= Δx/μe,hE, where μe,hare charge carries mobility.For validation, we assemble two CZT detectors (Redlen, Canada) as shown in Fig. 1. For the cross-strip one, the cathodes orient orthogonally to the anodes, to provide spatial information in two dimensions. The detectors were biased at 400 V. After preamplifier and shaping amplifier circuits, the outputs were connected to a high-speed free running ADC (CAEN, sampling rate 500MS/s, dynamic range 1V) to measure energy spectrum.The simulations and experimental results are illustrated in Fig. 2. The weighing potential has a pattern as shown in Fig. 2c, which is low near the cathode and rises rapidly when close to the anode. Such pattern is associated with the small pixel effect and single polarity sensing techniques, which affects both charge collection and temporal response of CZT detectors, as the function of different a/L ratio (pixel size to detector thickness). As a/L ratio decreases, the weighting potential shows a more abrupt change towards the anode region, which implies that the incomplete charge collection can be mitigated [4].The normalized charge collection, q(t)/q0, as a function of normalized time t/Th (Th is the maximum hole transit time through detector thickness L) for three heights is shown in Fig. 2d, where the sharp rising presents the electrons’ motion, and the flat trend presents the holes’ motion. A1 point has the best charge collection effective and the rising time is about 0.12Th; Points A2 and A3 are farther away from cathode due to poor hole mobility, so a longer collect time are needed (0.68Th and 0.82Th respectively), which means for CZT non-uniform responses are occurred in different depths, which can be used to obtain DOI information. While, for cross section of CZT (A2, B2, C2), the charge signal are more uniform as shown in Fig. 2e.The energy resolution is ~2.98±0.26% FWHM for 511 keV as shown in Fig. 2f, which is superior compared the typical value of 15-20% of a scintillation and PMT model. This result is based on a collimated beam of 511 keV gamma ray irradiating the whole pixel entering from the cathode side (i.e., interaction at all heights are included). In our future work, we will translate the beam along the Z direction to validate the detector performances again the analytical modeling. Reference [1] Hao Peng and Craig S Levin. “Design study of a high-resolution breast-dedicated PET system built system built from cadmium zinc telluride detectors”, Phys. Med. Biol., 55, pp. 2761-2788, 2010.[2] D Palubiak, MM El-Desouki, O Marinov, MJ Deen, Q Fang, “High-speed, single-photon avalanche-photodiode imager for biomedical applications”, IEEE Sensors Journal, 11, pp. 2401-2412, 2011.[3] S. Ramo, “Currents Induced by Electron Motion” Proc. IRE. 27, pp. 584-585, 1939.[4] Barrett, H.H. et al., “Charge Transport in Arrays of Semiconductor Gamma-Ray Detectors”,Phys. Rev. Lett, pp. 156-159, 1995

Improved mapping and quantification of serotonin transporter availability in the human brainstem with the HRRT

The serotonin system is involved in many physiological functions and clinical conditions. Serotonergic neurons originate from the raphe nuclei in the brainstem, and reliable estimates of receptor/transporter availability in the raphe in vivo are thus of interest. Though positron emission tomography (PET) can be used to quantify receptor distribution in the brain, high noise levels prevent reliable estimation of radioligand binding in small regions such as the raphe. For this purpose, parametric imaging in combination with high-resolution PET systems may provide images with reduced noise levels and sufficient contrast for reliable quantification. This study examined the potential to evaluate radioligand binding in brainstem nuclei, and assessed the effect of improved resolution on the outcome measures. For comparative purposes, radioligand binding was measured with an ECAT EXACT HR PET system (resolution about 4.5 mm FWHM) and a high-resolution research tomograph (HRRT) system (resolution about 1.5 mm FWHM). Six subjects were examined with both systems on the same day using the serotonin transporter radioligand [(11)C]MADAM. Parametric images of binding potential (BP (ND)) were obtained using a wavelet-aided approach. Regions of interest (ROIs) were delineated using a threshold-based semiautomatic delineation procedure for five brainstem structures. Regional BP (ND) values were estimated by applying the ROIs to the parametric images, and the percentage difference in BP (ND) between the systems was calculated. Signals for [(11)C]MADAM binding were obtained for all five brainstem structures. Overall, the HRRT provided 30-40 % higher BP (ND) values than the HR (p = 0.0017), independent of thresholds used in the ROI delineation procedure. The methodology used enabled the estimation of [(11)C]MADAM binding in the small nuclei of the brainstem. Differences in the BP (ND) values calculated using data from the two systems were mainly attributable to their differing resolutions. The estimated BP (ND) values provided lower across-subject variability than those previously obtained using compartment analysis. This procedure may therefore facilitate quantitative studies of receptor/transporter availability in the brainstem.

Study of a high-resolution, 3D positioning cadmium zinc telluride detector for PET

This paper investigates the performance of 1 mm resolution cadmium zinc telluride (CZT) detectors for positron emission tomography (PET) capable of positioning the 3D coordinates of individual 511 keV photon interactions. The detectors comprise 40 mm × 40 mm × 5 mm monolithic CZT crystals that employ a novel cross-strip readout with interspersed steering electrodes to obtain high spatial and energy resolution. The study found a single anode FWHM energy resolution of 3.06 ± 0.39% at 511 keV throughout most of the detector volume. Improved resolution is expected with properly shielded front-end electronics. Measurements made using a collimated beam established the efficacy of the steering electrodes in facilitating enhanced charge collection across anodes, as well as a spatial resolution of 0.44 ± 0.07 mm in the direction orthogonal to the electrode planes. Finally, measurements based on coincidence electronic collimation yielded a point spread function with 0.78 ± 0.10 mm FWHM, demonstrating 1 mm spatial resolution capability transverse to the anodes—as expected from the 1 mm anode pitch. These findings indicate that the CZT-based detector concept has excellent performance and shows great promise for a high-resolution PET system.

Extrastriatal dopamine D2 receptor binding in Huntington's disease

Huntington's disease (HD) is a neurodegenerative disorder, primarily affecting medium spiny neurones in the striatum. The density of striatal dopamine D(2) receptors is reduced in HD but there is little known about this biomarker in brain regions outside the striatum. The primary objective of this study was to compare extrastriatal dopamine D(2) receptor binding, in age-matched control subjects and patients with HD. All subjects were examined using a high-resolution positron emission tomography system and the high-affinity dopamine D(2) receptor radioligand [(11) C]FLB 457. A ROI based analysis was used with an atrophy correction method. Dopamine D(2) receptor binding potential was reduced in the striatum of patients with HD. Unlike the striatum, dopamine D(2) receptor binding in thalamic and cortical subregions was not significantly different from that in control subjects. A partial least square regression analysis which included binding potential values from all investigated cortical and subcortical regions revealed a significant model separating patients from controls, conclusively dependent on differences in striatal binding of the radioligand. Some clinical assessments correlated with striatal dopamine D(2) receptor binding, including severity of chorea and cognitive test performance. Hence, the present study demonstrates that dopamine D(2) receptors extrinsic to the striatum are well preserved in early to mid stage patients with HD. This observation may have implication for the development of therapy for HD.

Convex Optimization of Coincidence Time Resolution for a High-Resolution PET System

We are developing a dual panel breast-dedicated positron emission tomography (PET) system using LSO scintillators coupled to position sensitive avalanche photodiodes (PSAPD). The charge output is amplified and read using NOVA RENA-3 ASICs. This paper shows that the coincidence timing resolution of the RENA-3 ASIC can be improved using certain list-mode calibrations. We treat the calibration problem as a convex optimization problem and use the RENA-3's analog-based timing system to correct the measured data for time dispersion effects from correlated noise, PSAPD signal delays and varying signal amplitudes. The direct solution to the optimization problem involves a matrix inversion that grows order (n(3)) with the number of parameters. An iterative method using single-coordinate descent to approximate the inversion grows order (n). The inversion does not need to run to convergence, since any gains at high iteration number will be low compared to noise amplification. The system calibration method is demonstrated with measured pulser data as well as with two LSO-PSAPD detectors in electronic coincidence. After applying the algorithm, the 511 keV photopeak paired coincidence time resolution from the LSO-PSAPD detectors under study improved by 57%, from the raw value of 16.3 ±0.07 ns full-width at half-maximum (FWHM) to 6.92 ±0.02 ns FWHM ( 11.52 ±0.05 ns to 4.89 ±0.02 ns for unpaired photons).

Design study of a high-resolution breast-dedicated PET system built from cadmium zinc telluride detectors

We studied the performance of a dual-panel positron emission tomography (PET) camera dedicated to breast cancer imaging using Monte Carlo simulation. The proposed system consists of two 4 cm thick 12 × 15 cm2 area cadmium zinc telluride (CZT) panels with adjustable separation, which can be put in close proximity to the breast and/or axillary nodes. Unique characteristics distinguishing the proposed system from previous efforts in breast-dedicated PET instrumentation are the deployment of CZT detectors with superior spatial and energy resolution, using a cross-strip electrode readout scheme to enable 3D positioning of individual photon interaction coordinates in the CZT, which includes directly measured photon depth-of-interaction (DOI), and arranging the detector slabs edge-on with respect to incoming 511 keV photons for high photon sensitivity. The simulation results show that the proposed CZT dual-panel PET system is able to achieve superior performance in terms of photon sensitivity, noise equivalent count rate, spatial resolution and lesion visualization. The proposed system is expected to achieve ∼32% photon sensitivity for a point source at the center and a 4 cm panel separation. For a simplified breast phantom adjacent to heart and torso compartments, the peak noise equivalent count (NEC) rate is predicted to be ∼94.2 kcts s−1 (breast volume: 720 cm3 and activity concentration: 3.7 kBq cm−3) for a ∼10% energy window around 511 keV and ∼8 ns coincidence time window. The system achieves 1 mm intrinsic spatial resolution anywhere between the two panels with a 4 cm panel separation if the detectors have DOI resolution less than 2 mm. For a 3 mm DOI resolution, the system exhibits excellent sphere resolution uniformity (σrms/mean) ⩽ 10%) across a 4 cm width FOV. Simulation results indicate that the system exhibits superior hot sphere visualization and is expected to visualize 2 mm diameter spheres with a 5:1 activity concentration ratio within roughly 7 min imaging time. Furthermore, we observe that the degree of spatial resolution degradation along the direction orthogonal to the two panels that is typical of a limited angle tomography configuration is mitigated by having high-resolution DOI capabilities that enable more accurate positioning of oblique response lines.

Bayesian reconstruction of photon interaction sequences for high-resolution PET detectors

Realizing the full potential of high-resolution positron emission tomography (PET) systems involves accurately positioning events in which the annihilation photon deposits all its energy across multiple detector elements. Reconstructing the complete sequence of interactions of each photon provides a reliable way to select the earliest interaction because it ensures that all the interactions are consistent with one another. Bayesian estimation forms a natural framework to maximize the consistency of the sequence with the measurements while taking into account the physics of γ-ray transport. An inherently statistical method, it accounts for the uncertainty in the measured energy and position of each interaction. An algorithm based on maximum a posteriori (MAP) was evaluated for computer simulations. For a high-resolution PET system based on cadmium zinc telluride detectors, 93.8% of the recorded coincidences involved at least one photon multiple-interactions event (PMIE). The MAP estimate of the first interaction was accurate for 85.2% of the single photons. This represents a two-fold reduction in the number of mispositioned events compared to minimum pair distance, a simpler yet efficient positioning method. The point-spread function of the system presented lower tails and higher peak value when MAP was used. This translated into improved image quality, which we quantified by studying contrast and spatial resolution gains.

Evaluation of O-[18F]fluoromethyl-d-tyrosine as a radiotracer for tumor imaging with positron emission tomography

O-[(18)F]Fluoromethyl-D-tyrosine (D-[(18)F]FMT) has been reported as a potential tumor-detecting agent for positron emission tomography (PET). However, the reason why D-[(18)F]FMT is better than L-[(18)F]FMT is unclear. To clarify this point, we examined the mechanism of their transport and their suitability for tumor detection. The stereo-selective uptake and release of enantiomerically pure D- and L-[(18)F]FMT by rat C6 glioma cells and human cervix adenocarcinoma HeLa cells were examined. The results of a competitive inhibition study using various amino acids and a selective inhibitor for transport system L suggested that D-[(18)F]FMT, as well as L-[(18)F]FMT, was transported via system L, the large neutral amino acid transporter, possibly via LAT1. The in vivo distribution of both [(18)F]FMT and [(18)F]FDG in tumor-bearing mice and rats was imaged with a high-resolution small-animal PET system. In vivo PET imaging of D-[(18)F]FMT in mouse xenograft and rat allograft tumor models showed high contrast with a low background, especially in the abdominal and brain region. The results of our in vitro and in vivo studies indicate that L-[(18)F]FMT and D-[(18)F]FMT are specifically taken up by tumor cells via system L. D-[(18)F]FMT, however, provides a better tumor-to-background contrast with a tumor/background (contralateral region) ratio of 2.741 vs. 1.878 with the L-isomer, whose difference appears to be caused by a difference in the influence of extracellular amino acids on the uptake and excretion of these two isomers in various organs. Therefore, D-[(18)F]FMT would be a more powerful tool as a tumor-detecting agent for PET, especially for the imaging of a brain cancer and an abdominal cancer.

Design Considerations of Phoswich Detectors for High Resolution Positron Emission Tomography

A way to improve the spatial resolution in positron emission tomography (PET) is to determine the depth-of-interaction (DOI) in the detector. A way to achieve this is to use the phoswich approach, a detector with two or more layers of different scintillators. The layer identification is done by using differences in scintillation decay time and pulse shape discrimination techniques. The advantages of the concept have been demonstrated in the HRRT high resolution PET system using a LSO/LYSO combination giving a high spatial resolution uniformity of around 2.5 mm within a larger part of the imaged volume. A phoswich combination that lately has received attention is LuAP/LSO or LuYAP/LSO. The suggestions come from the crystal clear collaboration and there is a patent application for its use in PET. This particular combination of phoswich may, however, have a complication since both LuAP and LuYAP emit in the excitation band of LSO, thus making the functionality more complex. In the present paper we have looked into this and suggested different ways to overcome potential drawbacks.

Effects of system geometry and other physical factors on photon sensitivity of high-resolution positron emission tomography

We are studying two new detector technologies that directly measure the three-dimensional coordinates of 511 keV photon interactions for high-resolution positron emission tomography (PET) systems designed for small animal and breast imaging. These detectors are based on (1) lutetium oxyorthosilicate (LSO) scintillation crystal arrays coupled to position-sensitive avalanche photodiodes (PSAPD) and (2) cadmium zinc telluride (CZT). The detectors have excellent measured 511 keV photon energy resolutions (⩽12% FWHM for LSO-PSAPD and ⩽3% for CZT) and good coincidence time resolutions (2 ns FWHM for LSO-PSAPD and 8 ns for CZT). The goal is to incorporate the detectors into systems that will achieve 1 mm3 spatial resolution (∼1 mm3, uniform throughout the field of view (FOV)), with excellent contrast resolution as well. In order to realize 1 mm3 spatial resolution with high signal-to-noise ratio (SNR), it is necessary to significantly boost coincidence photon detection efficiency (referred to as photon sensitivity). To facilitate high photon sensitivity in the proposed PET system designs, the detector arrays are oriented ‘edge-on’ with respect to incoming 511 keV annihilation photons and arranged to form a compact FOV with detectors very close to, or in contact with, the subject tissues. In this paper, we used Monte Carlo simulation to study various factors that limit the photon sensitivity of a high-resolution PET system dedicated to small animal imaging. To optimize the photon sensitivity, we studied several possible system geometries for a fixed 8 cm transaxial and 8 cm axial FOV. We found that using rectangular-shaped detectors arranged into a cylindrical geometry does not yield the best photon sensitivity. This is due to the fact that forming rectangular-shaped detectors into a ring produces significant wedge-shaped inter-module gaps, through which Compton-scattered photons in the detector can escape. This effect limits the center point source photon sensitivity to <6% for a cylindrical system with rectangular-shaped blocks, 8 cm diameter and 8 cm axial FOV, and a 350–650 keV energy window setting. On the other hand, if the proposed rectangular-shaped detectors are arranged into an 8 × 8 × 8 cm3 FOV box configuration (four detector panels), there are only four inter-module gaps and the favorable distribution of these gaps yields >8% photon sensitivity for the LSO-PSAPD box configuration and >15% for CZT box geometry, using a 350–650 keV energy window setting. These simulation results compare well with analytical estimations. The trend is different for a clinical whole-body PET system that uses conventional LSO-PMT block detectors with larger crystal elements. Simulations predict roughly the same sensitivity for both box and cylindrical detector configurations. This results from the fact that a large system diameter (>80 cm) results in relatively small inter-module gaps in clinical whole-body PET. In addition, the relatively large block detectors (typically >5 × 5 cm2 cross-sectional area) and large crystals (>4 × 4 × 20 mm3) enable a higher fraction of detector scatter photons to be absorbed compared to a small animal system. However, if the four detector sides (panels) of a box-shaped system geometry are configured to move with respect to each other, to better fit the transaxial FOV to the actual size of the object to be imaged, a significant increase in photon sensitivity is possible. Simulation results predict a 60–100% relative increase of photon sensitivity for the proposed small animal PET box configurations and >60% increase for a clinical whole-body system geometry. Thus, simulation results indicate that for a PET system built from rectangular-shaped detector modules, arranging them into a box-shaped system geometry may help us to significantly boost photon sensitivity for both small animal and clinical PET systems.

Innovations technologiques récentes en détection pour la Tomographie par Emission de Positons

Since the recognition of the clinical value of Positron Emission Tomography (PET) for the diagnosis and staging of several cancers, the PET systems have evolved to systems associating PET and Computed Tomography (CT). The main constraint for clinical imaging is to reduce the acquisition duration. As a consequence, PET detectors are faster and emit more light than the BGO crystal used previously. These detectors allow an improvement of the count rate performance of the PET systems, reducing the scattered and the random events while increasing the true events at high activity concentration. Among the new crystals, some allow measuring the time of flight of the annihilation photons. This measurement further improves the performance of the systems. The spatial resolution of clinical PET systems is still equal to 5 mm at best. High spatial resolution PET systems dedicated to small animal imaging have been developed. These systems use similar crystal materials as the clinical systems. However, in order to permit spatial resolution close to 1 mm, the crystal elements have much smaller transverse dimensions than that of clinical systems. The detectors are compact using position sensitive photomultipliers or photodiodes. In order to preserve the uniformity of the spatial resolution over the transverse field of view of the tomographs, solutions allowing the measurement of the depth of interaction of the photons in the crystal have been designed. New compact detectors based on semi conductors are currently investigated.

A simple respiration gating technique and its application in high-resolution PET camera

We have developed a simple technique to gate positron emission tomography (PET) imaging in synchronization with respiratory motion to reduce image blurring caused by breathing and improve quantification of tracer uptake in lesions in the chest and abdomen, especially in very high-resolution PET systems. Taking advantage of the temperature differences in the air flow in a nostril due to inhalations and exhalations, a simple solid thermometer was used to construct a respiratory gating system to monitor the respiratory cycles. The gating system provided trigger signals synchronous with respiration and 40 Hz timing marks. These trigger signals and timing marks were inserted into the data stream in real-time while the PET camera was taking data. The gating trigger signals represent a particular phase of respiratory motion, and the evenly cycled timing marks were designed for motion-image frame registration. This gating system was implemented and tested with our MDAPET, a very high-resolution (2.7-mm resolution) PET camera developed at The University of Texas M. D. Anderson Cancer Center. A volunteer with 2 spherical lesion phantoms (diameters 3 mm and 5 mm) placed on the abdomen close to the navel was scanned in the gated mode. The respiration-gated images of the lesion phantoms were compared and studied. The simple respiratory gating system worked well in terms of detecting the breathing cycle and providing gating trigger signals and timing marks. Image blur and errors in the measurements of the lesions' volumes in the gated PET images were reduced, compared with those of the non-gated PET images.

Evaluation of coincidence plane definitions for improved volume resolution uniformity in PET

A new scheme for defining coincidence planes in positron emission tomography (PET) with the aim of improving the overall uniformity in volumetric spatial resolution has been investigated. The axial resolution in high-resolution PET systems rapidly degrades at off-center positions, in particular in tangential direction. This resolution loss is caused by the addition of coincidence planes with relatively large ring differences to form a single detection plane. Here, a different way of defining coincidence planes is evaluated to improve the overall spatial uniformity. This method only assigns coincidence combinations that fall within a specified slice thickness to contribute to a specific plane. The method produces overlapping axial planes, which allows a particular coincidence plane combination to contribute to several axial planes. Measurements of a point source at the center and at 20 cm off-center position showed a degradation in resolution from 4.6 to 12.4 mm full width at half-maximum (FWHM), tangentially using the conventional plane definition (max ring difference of eight). Using the new plane definition scheme (max ring difference of four), the resolution only degraded from 8.6 to 9.7 mm FWHM. This method should provide an improved resolution uniformity and image quality in particular for whole body PET.