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Time-of-flight (TOF) positron emission tomography (PET) detectors improve the signal-to-noise ratio of PET images by limiting the position of the generation of two 511 keV gamma-rays in space using the arrival time difference between the two photons. Unfortunately, bismuth germanate (BGO), widely used in conventional PET detectors, was limited as a TOF PET scintillator due to the relatively slow decay time of the scintillation photons. However, prompt Cerenkov light in BGO has been identified in addition to scintillation photons. Using Cerenkov photons for timing has significantly improved the coincidence timing resolution (CTR) of BGO. Based on this, further research on improving the CTR for a BGO-based TOF PET system is being actively conducted. Wrapping materials for BGO pixels have primarily employed white reflectors to most efficiently collect scintillation light. White reflectors have customarily been used as reflectors for BGO pixels even after Cerenkov light began to be utilized for timing calculations in pixel-level experiments. However, when the arrival-time differences of the two 511 keV annihilations photons were measured with pure Cerenkov radiators, painting the lateral sides of the radiators black can improve CTR by suppressing the reflection of Cerenkov photons. The use of BGO for TOF PET detectors requires simultaneously minimizing scintillation loss for good energy information and suppressing reflected Cerenkov photons for better timing performance. Thus, reflectors for BGO pixels should be optimized for better timing and energy performance. In this study, colored polytetrafluoroethylene (PTFE) tapes with discontinuous reflectance values at specific wavelengths were applied as a BGO reflector. We hypothesized that CTR could be enhanced by selectively suppressing reflected Cerenkov photons with an optimum colored reflector on the BGO pixel while minimizing scintillation photon loss. CTRs were investigated utilizing white and three colors (yellow, red, and green) PTFE tapes as a reflector. In addition, black-painted PTFE tape and enhanced specular reflector film were investigated as reference reflector materials. When 3 × 3 × 20 mm3 BGO pixels were wrapped with the yellow PTFE reflector, the CTR was significantly improved to 365 ± 5 ps from 403 ± 14 ps measured with the conventional white PTFE reflector. Adequate energy information was still obtained with only 4.1% degradation in light collection compared to the white reflector. Colored reflectors show the possibility to further improve CTR for BGO pixels with optimum reflectance design. [ABSTRACT FROM AUTHOR]

We are building a high sensitivity preclinical PET/MRI insert using a highly multiplexed light sharing PET module. Each module incorporates four 19 × 19 arrays of 1 × 1 × 20 mm3 LYSO crystals with dual-ended DOI encoding readout, requiring 32 readout channels for positioning and eight channels for timing. These constraints necessitate compact, robust electronics for digitization. We have characterized four linearized time-over-threshold circuits based on these detector requirements. The four circuits allow for high channel density and can digitize signals from highly multiplexed light sharing detectors. Each circuit digitizes one channel of a multiplexed SiPM array, yielding a binary output that interfaces directly with an FPGA. Using the optimal circuit, we have characterized the performance of a pair of PET modules. The four circuits were characterized based on linearity of the 22Na photopeak positions and energy resolution at 511 keV, as well as separation of elements in a 10 × 10 array of 1.2 mm LYSO crystals coupled with a specular reflector. Practical measures of performance were comparable to those obtained with a DRS evaluation board, which served as a reference acquisition system. The ratio of the 22Na photopeak positions was 2.0 for each circuit and the reference system, implying 20% saturation due to the SiPM. PET energy resolution of the optimal circuit was 11.8% FWHM for a single crystal versus 12.6% for the reference system, and crystals were equally well separated in all cases. PCBs implementing the optimal readout circuit were fabricated and used to construct two complete detector modules. Crystals in each of the four blocks in the module were well resolved, with a mean energy resolution of 24.4 ± 4.7%. Two modules operating in coincidence showed a single detector timing resolution of 3.0 ns, which is appropriate for preclinical applications. [ABSTRACT FROM AUTHOR]

A 194-cm-long total-body positron emission tomography/computed tomography (PET/CT) scanner (uEXPLORER), has been constructed to offer a transformative platform for human radiotracer imaging in clinical research and healthcare. Its total-body coverage and exceptional sensitivity provide opportunities for innovative studies of physiology, biochemistry, and pharmacology. The objective of this study is to develop a method to perform ultrahigh (100 ms) temporal resolution dynamic PET imaging by combining advanced dynamic image reconstruction paradigms with the uEXPLORER scanner. We aim to capture the fast dynamics of initial radiotracer distribution, as well as cardiac motion, in the human body. The results show that we can visualize radiotracer transport in the body on timescales of 100 ms and obtain motion-frozen images with superior image quality compared to conventional methods. The proposed method has applications in studying fast tracer dynamics, such as blood flow and the dynamic response to neural modulation, as well as performing real-time motion tracking (e.g., cardiac and respiratory motion, and gross body motion) without any external monitoring device (e.g., electrocardiogram, breathing belt, or optical trackers). [ABSTRACT FROM AUTHOR]

We are developing detectors for an un-collimated scanner for very high sensitivity single-photon imaging. The scanner consists of two large, thin, closely spaced, pixelated scintillation detectors of either thallium-doped sodium iodide (NaI(Tl)), sodium-doped cesium iodide (CsI(Na)), or bismuth germanate (BGO). The scintillator arrays are interchangeable to optimize performance for a wide range of isotope energies and imaging subjects. For each scintillator, flood histograms were obtained utilizing test gamma sources: ^109Cd, ^241Am, ^57Co, ^133Ba, ^137Cs, ^22Na, and beta source ^32Si. Using a 3 mm thick 21 \times 41 NaI(Tl) pixelated array (2~\mm \times 2~\mm pixels on a 2.2 mm pitch), read out by two adjacent Hamamatasu H8500 multi-channel photomultiplier tubes (MCPMTs), the energy resolution for ^57Co was 12.2% over the center of the MCPMTs and 45.3% for pixels over the gap, with flood histogram peak-to-valley ratios > \!\!\!\!6.1 for the center of the MCPMTs and > \!\!\!\!4.2 for the gap between the two MCPMTs. The NaI(Tl) detector consistently produced peak-to-valley ratios of >\!\!\!\! 1.6 in the center of the MCPMTs for all radioisotopes studied. CsI(Na) and BGO detectors had flood histograms of similar quality to NaI(Tl) at intermediate to high-energies, allowing for optimal imaging across a wide energy range. The measured sensitivity for point sources placed 10 mm from the detector approached 35% for low-energy isotopes and all scintillator materials, which results in an expected system sensitivity (two opposing detectors) of \sim \!\!70\% for these isotopes. The 5 mm thick BGO arrays had the greatest efficiency for high-energy isotopes due to the increased stopping power of this material. The measured spatial resolution for ^99m Tc for the CsI(Na) detector (1.6 mm pitch) was 7.5 mm FWHM at the aluminum entrance window (1.5 mm from scintillator face), decreasing to 15 mm at a distance of 5 mm from the scintillator face. The NaI(Tl) detector showed similar spatial resolution. This spatial resolution is sufficient for imaging well-localized radiotracer distributions in thin objects, and the very high sensitivity can be used for fast dynamic imaging, or imaging using very low injected doses. [ABSTRACT FROM AUTHOR]

In the development of positron emission tomography (PET) detectors, understanding and optimizing scintillator light collection is critical for achieving high performance, particularly when the design incorporates depth-of-interaction (DOI) encoding or time-of-flight information. Monte-Carlo simulations play an important role in guiding research in detector designs and popular software such as GATE now include models of light transport in scintillators. Although current simulation toolkits are able to provide accurate models of perfectly polished surfaces, they do not successfully predict light output for other surface finishes, for example those often used in DOI-encoding detectors. The lack of accuracy of those models mainly originates from a simplified description of rough surfaces as an ensemble of micro-facets determined by the distribution of their normal, typically a Gaussian distribution. The user can specify the standard deviation of this distribution, but this parameter does not provide a full description of the surface reflectance properties. We propose a different approach based on 3D measurements of the surface using atomic force microscopy. Polished and rough (unpolished) crystals were scanned to compute the surface reflectance properties. The angular distributions of reflectance and reflected rays were computed and stored in lookup tables (LUTs). The LUTs account for the effect of incidence angle and were integrated in a light transport model. Crystals of different sizes were simulated with and without reflector. The simulated maximum light output and the light output as a function of DOI showed very good agreement with experimental characterization of the crystals, indicating that our approach provides an accurate model of polished and rough surfaces and could be used to predict light collection in scintillators. This model is based on a true 3D representation of the surface, makes no assumption about the surface and provides insight on the optical behaviour of rough crystals that can play a critical role in optimizing the design of PET detectors. This approach is also compatible with existing simulation toolkits and next steps include the implementation in GATE. [ABSTRACT FROM AUTHOR]

The goal of this study was to evaluate the magnitude and origin of scattered radiation in a small-animal PET scanner and to assess the impact of these findings on noise equivalent count rate (NECR) measurements, a metric often used to optimize scanner acquisition parameters and to compare one scanner with another. The scatter fraction (SF) was measured for line sources in air and line sources placed within a mouse-sized phantom (25 mm ϕ × 70 mm) and a rat-sized phantom (60 mm ϕ × 150 mm) on the microPET II small-animal PET scanner. Measurements were performed for lower energy thresholds ranging from 150-450 keV and a fixed upper energy threshold of 750 keV. Four different methods were compared for estimating the SF. Significant scatter fractions were measured with just the line source in the field of view, with the spatial distribution of these events consistent with scatter from the gantry and room environment. For mouse imaging, this component dominates over object scatter, and the measured SF is strongly method dependent. The environmental SF rapidly increases as the lower energy threshold decreases and can be more than 30% for an open energy window of 150-750 keV. The object SF originating from the mouse phantom is about 3-4% and does not change significantly as the lower energy threshold in- creases. The object SF for the rat phantom ranges from 10 to 35% for different energy windows and increases as the lower energy threshold decreases. Because the measured SF is highly dependent on the method, and there is as yet no agreed upon standard for animal PET, care must be exercised when comparing NECR for small objects between different scanners. Differences may be methodological rather than reflecting any relevant difference in the performance of the scanner. Furthermore, these results have implications for scatter correction methods when the majority of the detected scatter does not arise from the object itself. [ABSTRACT FROM AUTHOR]

RECENT publicity about MRSA has highlighted the importance of hygiene systems in veterinary practices. Standard sanitary operating procedures (SSOPs) enable practices to ensure that cleaning is done as specified, that records are available to confirm this, and that corrective measures are taken if problems are found. Here, Simon Cherry outlines how to set up a system of SSOPs. [ABSTRACT FROM PUBLISHER]

We report our investigation of a positron emission tomography (PET) detector with 1 m spatial resolution. The prototype detector consists of a 9×9 array of 1×1×10 mm3 lutetium oxyorthosilicate (LSO) scintillator crystals coupled to Hamamatsu R5900-M64 or R5900-C12 position sensitive PMT by either optical fibers or an optical fiber bundle. With a 511 eV gamma source, the intrinsic spatial resolution of this detector was measured to be 0.92 mm. All crystals were well resolved in the flood source histogram. The measured energy and coincidence timing resolutions were around 26% and 4 ns, respectively, demonstrating that sufficient light can be extracted from these small crystals for PET applications. [Copyright &y& Elsevier]

Deals with the results of a depth of interaction (DOI) measurement of bending optical fibers and the light loss due to fiber bending. Amount of light loss due to fiber bending; Overview of DOI measurements; Discussion on the attenuation and scatter measurements.

Discusses a study which designed a small animal magnetic resonance (MR) compatible photon emission tomography (PET) (McPET) scanner for simultaneous PET and MR imaging of mice. Surface treatment of lutetium oxyorthosilicate (LSO) crystals; Result of the crystal coupling experiments; Significant difference between connectors made of different materials; Description of the proposed scanner.

Abstract. The aims of this study were: (1) to measure noninvasively and near simultaneously myocardial blood flow, oxygen consumption, and contractile function and (2) to analyze myocardial energy expenditure and efficiency at rest and during dobutamine stress in normal humans. Dynamic and gated carbon-11 acetate positron emission tomography (PET) imaging was performed in 11 normal subjects. The initial uptake of [sup 11]C-acetate was measured to estimate myocardial blood flow. Oxygen consumption was derived from the monoexponential slope of the [sup 11]C-clearance curve recorded during myocardial washout. ECG-gated systolic and diastolic images were acquired during the peak myocardial [sup 11]C activity to measure left ventricular radius, myocardial wall thickness, and long axis length. Myocardial oxygen consumption and parameters of cardiac geometry were used to determine myocardial energetics and cardiac efficiency by tension-area area analysis. Myocardial blood flow averaged 0.8+/-0.06 ml min[sup -1] g[sup -1] at rest and 1.48+/-0.15 ml min[sup -1] g[sup -1] during dobutamine stress. Oxygen delivery and consumption were 151+/-13 and 88+/-15 micro 1 O[sub 2] min[sup -1] g[sup -1] at rest and increased to 291+/-31 and 216+/-31 micro l O[sub 2] rain[sup -1] g[sup -1], respectively, during pharmacological stress (P<0.001). Oxygen extraction increased from 59%+/-8% at rest to 76%+/-9% during stress (P<0.001). Mechanical efficiency was 29%+/-6% at rest and 32%+/-6% during dobutamine stress (P=NS) while external work efficiency was 16%+/-6% at rest and increased to... [ABSTRACT FROM AUTHOR]

The author offers information regarding the accessing and subscription of the periodical. He mentions that the journal is owned by the Institute of Physics in Engineering and Medicine (IPEM) and published by Institute of Physics (IOP) Publishing. He further highlights several advantages of the periodical including free availability of the article and its low cost. He further informs about the professional staff of journal that handle paper receipt and interacts with reviewers and author.

The article presents a study on wearable whole-brain imaging device to asses rodent's behavior and brain functions. It says that the imaging technique provides a noninvasive window to envision a rodent's brain health and response to therapeutic interventions. It mentions several imaging technologies such as positron emission tomography (PET) and functional magnetic resonance imaging. It also features the study conducted by Daniela Schulz and colleagues on the use of wearable PET scanner in rat.

Background: Kinetic modeling of 18F-florbetaben provides important quantification of brain amyloid deposition in research and clinical settings but its use is limited by the requirement of arterial blood data for quantitative PET. The total-body EXPLORER PET scanner supports the dynamic acquisition of a full human body simultaneously and permits noninvasive image-derived input functions (IDIFs) as an alternative to arterial blood sampling. This study quantified brain amyloid burden with kinetic modeling, leveraging dynamic 18F-florbetaben PET in aorta IDIFs and the brain in an elderly cohort. Methods: 18F-florbetaben dynamic PET imaging was performed on the EXPLORER system with tracer injection (300 MBq) in 3 individuals with Alzheimer's disease (AD), 3 with mild cognitive impairment, and 9 healthy controls. Image-derived input functions were extracted from the descending aorta with manual regions of interest based on the first 30 s after injection. Dynamic time-activity curves (TACs) for 110 min were fitted to the two-tissue compartment model (2TCM) using population-based metabolite corrected IDIFs to calculate total and specific distribution volumes (VT, Vs) in key brain regions with early amyloid accumulation. Non-displaceable binding potential ( was also calculated from the multi-reference tissue model (MRTM). Results: Amyloid-positive (AD) patients showed the highest VT and VS in anterior cingulate, posterior cingulate, and precuneus, consistent with analysis. and VT from kinetic models were correlated (r² = 0.46, P < 2 with a stronger positive correlation observed in amyloid-positive participants, indicating reliable model fits with the IDIFs. VT from 2TCM was highly correlated ( = 0.65, P < 2 ) with Logan graphical VT estimation. Conclusion: Non-invasive quantification of amyloid binding from total-body 18F-florbetaben PET data is feasible using aorta IDIFs with high agreement between kinetic distribution volume parameters compared to in amyloid-positive and amyloid-negative older individuals. [ABSTRACT FROM AUTHOR]

A dual-ended readout PET detector based on two Hamamatsu 16 × 16 arrays of 1 × 1 mm2 SiPMs coupled to both ends of a 25 × 25 array of 0.69 × 0.69 × 20 mm3 polished LYSOs was evaluated in terms of flood histogram, energy resolution, timing resolution, and DOI resolution. The SiPM arrays have a pitch size of 1.2 mm. Each SiPM pixel has an active area of 1 × 1 mm2, and was fabricated using 15 μm microcells. The LYSO array has a pitch size of 0.75 mm, and the crystals are separated using Toray reflector with a thickness of 50 μm. The flood histogram and energy resolution were measured at different overvoltages (ranging from 1.5 to 7.0 V, in 0.5 V steps) and at four different temperatures (−7, 0, 10 and 20 °C). The timing resolution and DOI resolution were obtained at the optimal overvoltage for the flood histogram and at each different temperature. Overall, the results show better performance was obtained at lower temperatures, and that the optimal overvoltage decreased at higher temperatures. The optimal overvoltage was 5.0 V (corresponding to a bias voltage of 68.5 V) in order to achieve the highest quality flood histogram at 0 °C. Under these conditions, the flood histogram quality, energy resolution, timing resolution, and DOI resolution were 3.26 ± 0.65, 18.4 ± 4.5%, 1.70 ± 0.12 ns and 2.22 ± 0.19 mm, respectively. The flood histograms and energy resolution were also obtained at different activities. The results show that better flood histogram and energy resolution were obtained at lower activity, however all the crystals can be resolved at an event rate of over 210 k cps, indicating the DOI detector module can be used both for high resolution human brain PET and small animal PET applications. [ABSTRACT FROM AUTHOR]

The in vivo sensitivity limits and quantification performance of Cerenkov luminescence imaging have been studied using a tissue-like mouse phantom and 90Y. For a small, 9 mm deep target in the phantom, with no background activity present, the Cerenkov luminescence 90Y detection limit determined from contrast-to-noise ratios is 10 nCi for a 2 min exposure with a sensitive CCD camera and no filters. For quantitative performance, the values extracted from regions of interest on the images are linear within 5% of a straight line fit versus target activity for target activity of 70 nCi and above. The small branching ratio to decay with positron emission for 90Y also permits low-statistics PET imaging of the radionuclide. For PET imaging of the same phantom, with a small animal LSO detector-based scanner, the 90Y detection limit is approximately 3 orders of magnitude higher at 10 µCi. [ABSTRACT FROM AUTHOR]

The article focuses on the development of a noninvasive method for in vivo measurement of CD8+ T cell biodistribution and kinetics in humans using dynamic positron emission tomography (PET) and kinetic modeling. The study utilized an 89Zr-labeled CD8-targeted minibody and total-body PET imaging in COVID-19 convalescent patients and healthy individuals and the results demonstrated higher tissue-to-blood ratios in bone marrow of COVID-19 convalescent patients compared to controls.

The article reports that publishers of the journal "Physics in Medicine and Biology," IOP Publishing in association with the journal owners, the Institute of Physics and Engineering in Medicine (IPEM) have jointly been award the Roberts prize.

An introduction is presented in which the editor discusses various research papers within the issue on topics including nuclear medicine, bone marrow and protection from radiations.

Physics in Medicine and Biology (PMB) awards its ‘Citations Prize’ to the authors of the original research paper that has received the most citations in the preceding five years (according to the Institute for Scientific Information (ISI)). The lead author of the winning paper is presented with the Rotblat Medal (named in honour of Professor Sir Joseph Rotblat, a Nobel Prize winner who also was the second—and longest serving—Editor of PMB, from 1961–1972). The winner of the 2013 Citations Prize for the paper which has received the most citations in the previous five years (2008–2012) is Figure. Four of the prize winning authors. From left to right: Thomas Istel (Philips), Jens-Peter Schlomka (with medal, MorphoDetection), Ewald Roessl (Philips), and Gerhard Martens (Philips). Title: Experimental feasibility of multi-energy photon-counting K-edge imaging in pre-clinical computed tomography Authors: Jens Peter Schlomka1, Ewald Roessl1, Ralf Dorscheid2, Stefan Dill2, Gerhard Martens1, Thomas Istel1, Christian Bäumer3, Christoph Herrmann3, Roger Steadman3, Günter Zeitler3, Amir Livne4 and Roland Proksa1 Institutions: 1 Philips Research Europe, Sector Medical Imaging Systems, Hamburg, Germany 2 Philips Research Europe, Engineering & Technology, Aachen, Germany 3 Philips Research Europe, Sector Medical Imaging Systems, Aachen, Germany 4 Philips Healthcare, Global Research and Advanced Development, Haifa, Israel Reference: Schlomka et al 2008 Phys. Med. Biol. 53 4031–47 This paper becomes the first to win both this citations prize and also the PMB best paper prize (The Roberts Prize), which it won for the year 2008. Discussion of the significance of the winning paper can be found in this medicalphysicsweb article from the time of the Roberts Prize win (http://medicalphysicsweb.org/cws/article/research/39907). The author's enthusiasm for their prototype spectral CT system has certainly been reflected in the large number of citations the paper subsequently has received. Our warm congratulations go to the winning authors. [ABSTRACT FROM AUTHOR]

Over several months, representatives from the U.S. Department of Energy (DOE) Office of Science and National Institutes of Health (NIH) had a number of meetings that lead to the conclusion that innovations in the Nation’s health care could be realized by more directed interactions between NIH and DOE. It became clear that the expertise amassed and instrumentation advances developed at the DOE physical science laboratories to enable cutting-edge research in particle physics could also feed innovation in medical healthcare.To meet their scientific mission, the DOE laboratories created advances in such technologies as particle beam generation, radioisotope production, high-energy particle detection and imaging, superconducting particle accelerators, superconducting magnets, cryogenics, high-speed electronics, artificial intelligence, and big data. To move forward, NIH and DOE initiated the process of convening a joint workshop which occurred on July 12th and 13th, 2021. This Special Report presents a summary of the findings of the collaborative workshop and introduces the goals of the next one. [ABSTRACT FROM AUTHOR]

• ID-IF from small blood vessels can be used to guide blood input function estimation for brain parametric imaging. • A kernel method was developed for simultaneous estimation of blood input function. • uEXPLORER total-body PET system was used for validation where the reference input function can be extracted from major blood pools. Dynamic PET allows quantification of physiological parameters through tracer kinetic modeling. For dynamic imaging of brain or head and neck cancer on conventional PET scanners with a short axial field of view, the image-derived input function (ID-IF) from intracranial blood vessels such as the carotid artery (CA) suffers from severe partial volume effects. Alternatively, optimization-derived input function (OD-IF) by the simultaneous estimation (SIME) method does not rely on an ID-IF but derives the input function directly from the data. However, the optimization problem is often highly ill-posed. We proposed a new method that combines the ideas of OD-IF and ID-IF together through a kernel framework. While evaluation of such a method is challenging in human subjects, we used the uEXPLORER total-body PET system that covers major blood pools to provide a reference for validation. The conventional SIME approach estimates an input function using a joint estimation together with kinetic parameters by fitting time activity curves from multiple regions of interests (ROIs). The input function is commonly parameterized with a highly nonlinear model which is difficult to estimate. The proposed kernel SIME method exploits the CA ID-IF as a priori information via a kernel representation to stabilize the SIME approach. The unknown parameters are linear and thus easier to estimate. The proposed method was evaluated using 18F-fluorodeoxyglucose studies with both computer simulations and 20 human-subject scans acquired on the uEXPLORER scanner. The effect of the number of ROIs on kernel SIME was also explored. The estimated OD-IF by kernel SIME showed a good match with the reference input function and provided more accurate estimation of kinetic parameters for both simulation and human-subject data. The kernel SIME led to the highest correlation coefficient (R = 0.97) and the lowest mean absolute error (MAE = 10.5 %) compared to using the CA ID-IF (R = 0.86, MAE = 108.2 %) and conventional SIME (R = 0.57, MAE = 78.7 %) in the human-subject evaluation. Adding more ROIs improved the overall performance of the kernel SIME method. The proposed kernel SIME method shows promise to provide an accurate estimation of the blood input function and kinetic parameters for brain PET parametric imaging. [ABSTRACT FROM AUTHOR]

Purpose: Depth encoding detectors are required to improve the spatial resolution and spatial resolution uniformity of small animal positron emission tomography (PET) scanners, as well as dedicated breast and brain scanners. Depth of interaction (DOI) can be measured by using dual-ended readout of lutetium oxyorthosilicate (LSO) scintillator arrays with position-sensitive avalanche photodiodes. Inter-crystal reflectors and crystal surface treatments play important roles in determining the performance of dual-ended detectors. In this paper, the authors evaluated five LSO arrays made with three different intercrystal reflectors and with either polished or unpolished crystal surfaces. Methods: The crystal size in all arrays was 1.5 mm, which is typical of the detector size used in small animal and dedicated breast scanners. The LSO arrays were measured with dual-ended readout and were compared in terms of flood histogram, energy resolution, and DOI resolution performance. Results: The four arrays using enhanced specular reflector (ESR) and Toray reflector provided similar quality flood histograms and the array using Crystal Wrap reflector gave the worst flood histogram. The two arrays using ESR reflector provided the best energy resolution and the array using Crystal Wrap reflector yielded the worst energy resolution. All arrays except the polished ESR array provided good DOI resolution ranging from 1.9 mm to 2.9 mm. DOI resolution improved as the gradient in light collection efficiency with depth (GLCED) increased. The geometric mean energies were also calculated for these dual-ended readout detectors as an alternative to the conventional summed total energy. It was shown that the geometric mean energy is advantageous in that it provides more uniform photopeak amplitude at different depths for arrays with high GLCED, and is beneficial in event selection by allowing a fixed energy window independent of depth. A new method of DOI calculation that improved the linearity of DOI ratio vs depth and simplifies the DOI calibration procedure also was developed and tested. Conclusions: The results of these studies provide useful guidance in selecting the proper reflectors and crystal surface treatments when LSO arrays are used for high-resolution PET applications in small animal scanners or dedicated breast and brain scanners. [ABSTRACT FROM AUTHOR]

Glia account for 90% of human brain cells and have a significant role in brain homeostasis. Thus, specific in vivo imaging markers of glial metabolism are potentially valuable. In the brain, 2-fluoroacetate is selectively taken up by glial cells and becomes metabolically trapped in the tricarboxylic acid cycle. Recent work in rodent brain injury models demonstrated elevated lesion uptake of 2-[18F]fluoroacetate ([18F]FACE), suggesting possible use for specifically imaging glial metabolism. To assess this hypothesis, we evaluated [18F]FACE kinetics in rodent models of cerebral hypoxia-ischemia at 3 and 24 hours post insult. Lesion uptake was significantly higher at 30 minutes post injection (P<0.05). An image-based method for input function estimation using cardiac blood was validated. Analysis of whole blood showed no significant metabolites and plasma activity concentrations of ∼50% that of whole blood. Kinetic models describing [18F]FACE uptake were developed and quantitatively compared. Elevated [18F]FACE uptake was found to be driven primarily by K1/k2 rather than k3, but changes in the latter were detectable. The two-tissue irreversible uptake model (2T3k) was found to be necessary and sufficient for modeling [18F]FACE uptake. We conclude that kinetic modeling of [18F]FACE uptake represents a potentially useful tool for interrogation of glial metabolism. [ABSTRACT FROM AUTHOR]

X-ray luminescence optical tomography (XLOT) is an emerging hybrid imaging modality in which x-ray excitable particles (phosphor particles) emit optical photons when stimulated with a collimated x-ray beam. XLOT can potentially combine the high sensitivity of optical imaging with the high spatial resolution of x-ray imaging. For reconstruction of XLOT data, we compared two reconstruction algorithms, conventional filtered backprojection (FBP) and a new algorithm, x-ray luminescence optical tomography with excitation priors (XLOT-EP), in which photon propagation is modeled with the diffusion equation and the x-ray beam positions are used as reconstruction priors. Numerical simulations based on dose calculations were used to validate the proposed XLOT imaging systemand the reconstruction algorithms. Simulation results showed nanoparticle concentrations reconstructed with XLOT-EP are much less dependent on scan depth than those obtained with FBP. Measurements at just two orthogonal projections are sufficient for XLOT-EP to reconstruct an XLOT image for simple source distributions. The heterogeneity of x-ray energy deposition is included in the XLOT-EP reconstruction and improves the reconstruction accuracy, suggesting that there is a need to calculate the x-ray energy distribution for experimental XLOT imaging. [ABSTRACT FROM AUTHOR]

Driven by a need for high and uniform spatial resolution, as well as depth correction to improve time-of-flight PET, the design of PET detectors with depth-of-interaction (DOI) information is of great interest. To combine the advantages of continuous DOI information with a single-ended readout of the crystal, we have proposed a solution based on the use of phosphor-coated crystals. Here we build on our initial work to optimize the coating process and detector design, thus taking a significant step towards making this approach practical. We implemented a new method to coat 20 mm-long unpolished LSO crystals with a mixture of YAG phosphor powder and UV-curable optical cement that provides accurate, robust, and reproducible coatings. Using this new coating process, critical parameters such as coating thickness, coating shape, and crystal size were studied. The performance of different coating configurations was evaluated by recording pulses at different irradiation depths and extracting the decay time of individual pulses. The delayed charge integration method was used to characterize the pulses acquired at various DOI. The coating thickness was decreased from 250~\mum (previous work) to 50~\mu m with minimal degradation in performance. 100~\mu m-thick coating provided the best trade-off between performance and additional volume around the crystal, which will be important to build crystal arrays with high packing fraction. Additionally, varying the coating length on the different crystal faces allowed for better DOI encoding along the crystal length, when compared to previous coating configurations. Crystal face sizes ranging from 2 mm \times 2 mm to 5 mm \times 5 mm were studied; best performance was obtained with the 2 mm \times 2 mm crystals. [ABSTRACT FROM PUBLISHER]

Highlights: [•] Subsystem coupling in a combined PET/MR small animal MRI is investigated. [•] A grounding scheme is developed to increase isolation between the sub systems. [•] Carbon fiber material provides good RF shielding without supporting eddy currents. [•] Isolation also depends on the location of the PET electronics inside the gradients. [•] Chemical shift imaging is used to image eddy current effects. [ABSTRACT FROM AUTHOR]

Objective: Dual-ended readout depth-encoding detectors based on bismuth germanate (BGO) scintillation crystal arrays are good candidates for high-sensitivity small animal positron emission tomography used for very-low-dose imaging. In this paper, the performance of three dual-ended readout detectors based on 15 × 15 BGO arrays with three different reflector arrangements and 8 × 8 silicon photomultiplier arrays were evaluated and compared. Approach: The three BGO arrays, denoted wo-ILG (without internal light guide), wp-ILG (with partial internal light guide), and wf-ILG (with full internal light guide), share a pitch size of 1.6 mm and thickness of 20 mm. Toray E60 with a thickness of 50 μ m was used as inter-crystal reflector. All reflector lengths in the wo-ILG and wf-ILG BGO arrays were 20 and 18 mm, respectively; the reflectors in the wp-ILG BGO array were 18 mm at the central region of the array and 20 mm at the edge. By using 18 mm reflectors, part of the crystals in the wp-ILG and wf-ILG BGO arrays worked as internal light guides. Main results: The results showed that the detector based on the wo-ILG BGO array provided the best flood histogram. The energy, timing and DOI resolutions of the three detectors were similar. The energy resolutions full width at half maximum (FWHM value) based on the wo-ILG, wp-ILG and wf-ILG BGO arrays were 27.2 ± 3.9%, 28.7 ± 4.6%, and 29.5 ± 4.7%, respectively. The timing resolutions (FWHM value) were 4.7 ± 0.5 ns, 4.9 ± 0.5 ns, and 5.0 ± 0.6 ns, respectively. The DOI resolution (FWHM value) were 3.0 ± 0.2 mm, 2.9 ± 0.2 mm, and 3.0 ± 0.2 mm, respectively. Over all, the wo-ILG detector provided the best performance. [ABSTRACT FROM AUTHOR]

As the field of molecular imaging evolves and increasingly is asked to fill the discovery and validation space between basic science and clinical applications, careful consideration should be given to the models in which studies are conducted. The MIN-O mouse model series is an established in vivo model of human mammary precancer ductal carcinoma in situ with progression to invasive carcinoma. This series of transplant lines is propagated in vivo and experiments utilizing this model can be completed in non-engineered immune intact FVB/n wild type mice thereby modeling the tumor microenvironment with biological relevance superior to traditional tumor cell xenografts. Unfortunately, the same qualities that make this and many other transplant lines more biologically relevant than standard cell lines for molecular imaging studies present a significant obstacle as somatic genetic re-engineering modifications common to many imaging applications can be technically challenging. Here, we describe a protocol for the efficient lentiviral transduction of cell slurries derived from precancerous MIN-O lesions, in vitro culture of ''MIN-O-spheres'' derived from single cell clones, and the subsequent transplantation of these spheres to produce transduced sublines suitable for optical imaging applications. These lines retain the physiologic and pathologic properties, including multilineage differentiation, and complex microanatomic interaction with the host stroma characteristic of the MIN-O model. We also present the in vivo imaging and immunohistochemical analysis of serial transplantation of one such subline and detail the progressive multifocal loss of the transgene in successive generations. [ABSTRACT FROM AUTHOR]

A new approach to depth of interaction (DOI) encoding for a pixelated LSO array using a single multi-channel PMT was investigated. In this method the DOI information was estimated by taking advantage of optical crosstalk between LSO elements and examining the standard deviation (spread) of signals on all channels of the PMT. Unpolished and polished 6 × 6 LSO arrays with a crystal size of 1.3 × 1.3 × 20 mm3 were evaluated on a Hamamatsu H7546 64-channel PMT. The arrays were placed on the center of the PMT and the central 16 channels of the PMT were individually read out and digitized. For the unpolished array, all crystals were resolved in the flood histogram. An average DOI resolution of 8 mm was obtained. The energy resolution was 25% after the signal amplitude was corrected using the measured DOI information. For the polished array, the flood histogram was superior to the unpolished array, however no DOI information could be measured. Using unpolished crystals, this method could be a practical way to achieve limited DOI information in PET detectors. The standard deviation of all PMT channels can be readily obtained using a resistor network. Only five signals (four signals to determine the x-y position and one signal measuring the standard deviation) need to be digitized, and this method only requires a single photon detector to read out the array. Unlike phoswich detectors, the method does not require segmenting the scintillator array into layers. The measured DOI resolution was much worse than that obtained with the dual-ended readout method, however, it was similar to that obtained with a two-layer phoswich detector. [ABSTRACT FROM AUTHOR]

Abstract: Longitudinal analysis of animals with neonatal brain lesions enables the evaluation of behavioral changes during multiple stages of development. Interpretation of such changes, however, carries the caveat that permanent neural injury also yields morphological and neurochemical reorganization elsewhere in the brain that may lead either to functional compensation or to exacerbation of behavioral alterations. We have measured the long-term effects of selective neonatal brain damage on resting cerebral glucose metabolism in nonhuman primates. Sixteen rhesus monkeys (Macaca mulatta) received neurotoxic lesions of either the amygdala (n =8) or hippocampus (n =8) when they were two weeks old. Four years later, these animals, along with age- and experience-matched sham-operated control animals (n =8), were studied with high-resolution positron emission tomography (microPET) and 2-deoxy-2[18F]fluoro-d-glucose ([18F]FDG) to detect areas of altered metabolism. The groups were compared using an anatomically-based region of interest analysis. Relative to controls, amygdala-lesioned animals displayed hypometabolism in three frontal lobe regions, as well as in the neostriatum and hippocampus. Hypermetabolism was also evident in the cerebellum of amygdala-lesioned animals. Hippocampal-lesioned animals only showed hypometabolism in the retrosplenial cortex. These results indicate that neonatal amygdala and hippocampus lesions induce very different patterns of long-lasting metabolic changes in distant brain regions. These observations raise the possibility that behavioral alterations in animals with neonatal lesions may be due to the intended damage, to consequent brain reorganization or to a combination of both factors. [Copyright &y& Elsevier]

The use of micro-CT in small animals has increased in recent years. Although the radiation levels used for micro-CT are generally not lethal to the animal, they are high enough where changes in the immune response and other biological pathways may alter the experimental outcomes. Therefore, it is important to understand what the doses are for a specific imaging procedure. Monte Carlo simulation was used to evaluate the radiation dose to small animals (5 – 40 mm in diameter) as a result of X-ray exposure. Both monoenergetic (6 – 100 keV) and polyenergetic (15 – 100 kVp) X-ray sources were simulated under typical mouse imaging geometries. X-ray spectral measurements were performed on a mouse imaging X-ray system using a commercially available X-ray spectrometer, and spectra from high-energy systems were used as well. For a typical X-ray system with 1.0 mm of added Al at 40 kVp, the dose coefficients (dose to mouse per air kerma at isocenter) were 0.80, 0.63, 0.52, and 0.44 mGy/mGy for mouse diameters of 10, 20, 30, and 40 mm, respectively. A number of tables and figures are provided for dose estimation over a range of mouse imaging geometries. [ABSTRACT FROM AUTHOR]

This article is part of the Topical Collection on Technology Introduction Thanks to companies' research and development processes, frequently involving fruitful partnerships with academic centres, and what could be acknowledged as welcome competition between PET vendors, new PET hardware and software technologies are regularly innovated and released as clinic-ready products. Advanced PET detectors Pushing the limit of detectability More recently, silicon photomultiplier (SiPM) technology has become available from the major PET vendors. Another important consideration is that PET technology is in constant development and rapidly evolving, the latest to date being SiPM PETs system and total-body PET. There were lesions only identified using the SiPM PET/CT showing that SiPM PET/CT has superior performance compared to a conventional PET/CT scanner [[41]]. Total-body PET Anybody involved in designing or analysing PET studies recognizes that limited detection sensitivity, and its consequence of image noise, is by far the biggest technical limitation in PET imaging, whether that be in clinical PET or in research studies. [Extracted from the article]

Positron emission tomography (PET) plays an increasingly important role in research and clinical applications, catalysed by remarkable technical advances and a growing appreciation of the need for reliable, sensitive biomarkers of human function in health and disease. Over the last 30 years, a large amount of the physics and engineering effort in PET has been motivated by the dominant clinical application during that period, oncology. This has led to important developments such as PET/CT, whole-body PET, 3D PET, accelerated statistical image reconstruction, and time-of-flight PET. Despite impressive improvements in image quality as a result of these advances, the emphasis on static, semi-quantitative 'hot spot' imaging for oncologic applications has meant that the capability of PET to quantify biologically relevant parameters based on tracer kinetics has not been fully exploited. More recent advances, such as PET/MR and total-body PET, have opened up the ability to address a vast range of new research questions, from which a future expansion of applications and radiotracers appears highly likely. Many of these new applications and tracers will, at least initially, require quantitative analyses that more fully exploit the exquisite sensitivity of PET and the tracer principle on which it is based. It is also expected that they will require more sophisticated quantitative analysis methods than those that are currently available. At the same time, artificial intelligence is revolutionizing data analysis and impacting the relationship between the statistical quality of the acquired data and the information we can extract from the data. In this roadmap, leaders of the key sub-disciplines of the field identify the challenges and opportunities to be addressed over the next ten years that will enable PET to realise its full quantitative potential, initially in research laboratories and, ultimately, in clinical practice. [ABSTRACT FROM AUTHOR]

With the goal of developing a total-body small-animal PET system with a high spatial resolution of ∼0.5 mm and a high sensitivity >10% for mouse/rat studies, we simulated four scanners using the graphical processing unit-based Monte Carlo simulation package (gPET) and compared their performance in terms of spatial resolution and sensitivity. We also investigated the effect of depth-of-interaction (DOI) resolution on the spatial resolution. All the scanners are built upon 128 DOI encoding dual-ended readout detectors with lutetium yttrium oxyorthosilicate (LYSO) arrays arranged in 8 detector rings. The solid angle coverages of the four scanners are all ∼0.85 steradians. Each LYSO element has a cross-section of 0.44 × 0.44 mm2 and the pitch size of the LYSO arrays are all 0.5 mm. The four scanners can be divided into two groups: (1) H2RS110-C10 and H2RS110-C20 with 40 × 40 LYSO arrays, a ring diameter of 110 mm and axial length of 167 mm, and (2) H2RS160-C10 and H2RS160-C20 with 60 × 60 LYSO arrays, a diameter of 160 mm and axial length of 254 mm. C10 and C20 denote the crystal thickness of 10 and 20 mm, respectively. The simulation results show that all scanners have a spatial resolution better than 0.5 mm at the center of the field-of-view (FOV). The radial resolution strongly depends on the DOI resolution and radial offset, but not the axial resolution and tangential resolution. Comparing the C10 and C20 designs, the former provides better resolution, especially at positions away from the center of the FOV, whereas the latter has 2× higher sensitivity (∼10% versus ∼20%). This simulation study provides evidence that the 110 mm systems are a good choice for total-body mouse studies at a lower cost, whereas the 160 mm systems are suited for both total-body mouse and rat studies. [ABSTRACT FROM AUTHOR]

Assessing the position of the Bragg peak (BP) in hadron radiotherapy utilizing prompt-gamma imaging (PGI) presents many challenges in terms of detector physics. Gamma detectors with the capability of extracting the best energy, timing, and spatial information from each gamma interaction, as well as with high detection efficiency and count rate performance, are needed for this application. In this work we present the characterization of a pixel Čerenkov charge induction (CCI) thallium bromide (TlBr) detector in terms of energy and and electron drift time for its potential use in PGI. The CCI TlBr detector had dimensions of 4 × 4 × 5 mm3 and one of its electrodes was segmented in pixels with 1.7 mm pitch. A silicon photomultiplier (SiPM) was optically coupled to one of the faces of the TlBr slab to read out the Čerenkov light promptly emitted after the interaction of a gamma ray. The detector was operated stand-alone and the 1.275 prompt gammas from a 22Na radioactive source were used for the study. The electron drift time was obtained by combining the Čerenkov and charge induction signals and then used as a measure of the depth of interaction. The electron mobility in TlBr was estimated as ∼27 cm2 V−1 s−1. Energy resolutions between 3.4% and 4.0% at 1.275 MeV were obtained after depth-correction. These values improved to 3.0%–3.3% when events with drift times of 3–6 μs were selected. These results show the potential of pixel CCI TlBr detectors to resolve gamma interactions in the detector with mm-like accuracy in 3D and with excellent energy resolution. Previous studies with CCI TlBr devices have shown a timing resolution of <400 ps full width at half maximum when detecting 511 keV gamma rays, therefore, the timing accuracy is expected to improve with the increased energy of the gamma rays in PGI. While other important detector characteristics such as count rate capability remain to be studied, results from this work combined with other preliminary data show pixel CCI detectors can simultaneously provide excellent energy, timing, and spatial resolution performance and are a very promising option for PGI in hadron therapy. [ABSTRACT FROM AUTHOR]

The performance of dual-ended readout depth-encoding positron emission tomography (PET) detectors based on bismuth germanate (BGO) coupled to silicon photomultipliers (SiPM) arrays was measured for the first time and compared to lutetium-yttrium oxyorthosilicate (LYSO)-based detectors using the same readout. The BGO and LYSO crystal arrays all had a crystal pitch of 2.2 mm and were coupled to 8 × 8 SiPM arrays with a matching pitch of 2.2 mm, using a one-to-one coupling configuration. Three types of crystals with Toray reflector were used: polished LYSO, polished BGO, and unpolished BGO, and for two different crystal thicknesses of 20 mm and 30 mm. All the crystal elements in the BGO arrays were clearly resolved in the flood histogram. Better flood histograms were obtained using the LYSO arrays for a selected crystal thickness, and better flood histograms were obtained using the 20 mm thick crystal arrays for a selected crystal type. The average crystal level energy resolution and timing resolution for 20 mm polished LYSO, polished BGO and unpolished BGO crystals at their optimal SiPM bias voltage were 18.6 ± 1.3% and 1.19 ± 0.20 ns, 17.8 ± 0.8% and 4.43 ± 0.47 ns, and 18.0 ± 1.0% and 4.68 ± 1.0 ns, respectively. Depth-of-interaction (DOI) resolution of the 20 mm polished LYSO array was 2.31 ± 0.17 mm and for the 20 mm unpolished BGO array was 3.53 ± 0.25 mm. However, polished BGO arrays with Toray reflector did not provide DOI information. Our key conclusion is that dual-ended readout depth-encoding 20 mm thick unpolished BGO detectors are good candidates for low-activity PET systems with small field-of-view and low timing performance requirements, such as preclinical or compact organ-dedicated PET systems, with the advantage over LYSO of having no background radiation and significantly lower cost. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) using scanners incorporating lutetium-based (Lu-based) scintillators are widely used in nuclear medicine. However their application in imaging very low (<100 kBq) activity distributions is quite limited due to the intrinsic 176Lu radiation emitted from the scintillators. To visualize very low activities, 176Lu background needs to be reduced or removed. This study proposes a classification method to select background coincidences from true coincidences arising from the source by supervised learning using the optimal classifier as determined by investigating 5 different classifiers: logistic regression, support vector machine, random forest, extreme gradient boosting (XGBoost) and deep neural network. Five energy and time-of-flight (TOF) related features from each coincidence event are extracted to form the training and test set in the classification. The proposed method was verified on a pair of TOF-PET detector modules. Since the measured source coincidences cannot be differentiated from the background events experimentally, simulated source coincidences are used to train the classification model. The simulated feature spectra are therefore compared with those obtained from measurement to verify the feasibility of classifying measured coincidences using a model learned by simulation. XGBoost classifier performed most effectively in classifying the coincidences and provided impressively high classification accuracy (>99%). It was subsequently tested by imaging point-like source, planar Derenzo and bar phantoms with the pair of TOF-PET detectors. An 89.4% image contrast enhancement for the Derenzo phantom at an activity concentration of 100 Bq mm−2, and a 52.4% peak-to-valley ratio improvement across the area of bar phantom at a concentration of 25 Bq mm−2, were observed on the reconstructed images with XGBoost classification applied. The proposed method could extend the usage of Lu-based PET scanners to very low activity detection and imaging and has the potential to be used in a variety of molecular imaging tasks to detect low-level signals. [ABSTRACT FROM AUTHOR]

The emergence of PET probes for amyloid plaques and neurofibrillary tangles, hallmarks of Alzheimer disease (AD), enables monitoring of pathology in AD mouse models. However, small-animal PET imaging is limited by coarse spatial resolution. We have installed a custom-fabricated PET insert into our small-animal MRI instrument and used PET/MRI hybrid imaging to define regions of amyloid vulnerability in 5xFAD mice. We compared fluorine-18 [18F]-Florbetapir uptake in the 5xFAD brain by dedicated small-animal PET/MRI and PET/CT to validate the quantitative measurement of PET/MRI. Next, we used PET/MRI to define uptake in six brain regions. As expected, uptake was comparable to wild-type in the cerebellum and elevated in the cortex and hippocampus, regions implicated in AD. Interestingly, uptake was highest in the thalamus, a region often overlooked in AD studies. Development of small-animal PET/MRI enables tracking of brain region-specific pathology in mouse models, which may prove invaluable to understanding AD progression and therapeutic development. [ABSTRACT FROM AUTHOR]

Purpose: Knowing the precise flow of cerebrospinal fluid (CSF) is important in the management of multiple neurological diseases. Technology for non-invasively quantifying CSF flow would allow for precise localization of injury and assist in evaluating the viability of certain devices placed in the central nervous system (CNS). Methods: We describe a near-infrared fluorescent dye for accurately monitoring CSF flow by positron emission tomography (PET) and fluorescence. IR-783, a commercially available near-infrared dye, was chemically modified and radiolabeled with fluorine-18 to give [18F]-IR783-AMBF3. [18F]-IR783-AMBF3 was intrathecally injected into the rat models with normal and aberrant CSF flow and evaluated by the fluorescence and PET/MRI or PET/CT imaging modes. Results: IR783-AMBF3 was clearly distributed in CSF-containing volumes by PET and fluorescence. We compared IR783-AMBF3 (fluorescent at 778/793 nm, ex/em) to a shorter-wavelength, fluorescein equivalent (fluorescent at 495/511 nm, ex/em). IR783-AMBF3 was superior for its ability to image through blood (hemorrhage) and for imaging CSF-flow, through-skin, in subdural-run lumboperitoneal shunts. IR783-AMBF3 was safe under the tested dosage both in vitro and in vivo. Conclusion: The superior imaging properties of IR783-AMBF3 could lead to enhanced accuracy in the treatment of patients and would assist surgeons in non-invasively diagnosing diseases of the CNS. [ABSTRACT FROM AUTHOR]

Social bonds, especially attachment relationships, are crucial to our health and happiness. However, what we know about the neural substrates of these bonds is almost exclusively limited to rodent models and correlational experiments in humans. Here, we used socially monogamous non-human primates, titi monkeys ( Callicebus cupreus ) to experimentally examine changes in regional and global cerebral glucose metabolism (GCGM) during the formation and maintenance of pair bonds. Baseline positron emission tomography (PET) scans were taken of thirteen unpaired male titi monkeys. Seven males were then experimentally paired with females, scanned and compared, after one week, to six age-matched control males. Five of the six control males were then also paired and scanned after one week. Scans were repeated on all males after four months of pairing. PET scans were coregistered with structural magnetic resonance imaging (MRI), and region of interest (ROI) analysis was carried out. A primary finding was that paired males showed a significant increase in [ 18 F]-fluorodeoxyglucose (FDG) uptake in whole brain following one week of pairing, which is maintained out to four months. Dopaminergic, “motivational” areas and those involved in social behavior showed the greatest change in glucose uptake. In contrast, control areas changed only marginally more than GCGM. These findings confirm the large effects of social bonds on GCGM. They also suggest that more studies should examine how social manipulations affect whole-brain FDG uptake, as opposed to assuming that it does not change across condition. [ABSTRACT FROM AUTHOR]

Pair bonding leads to increases in dopamine D1 receptor (D1R) binding in the nucleus accumbens of monogamous prairie voles. In the current study, we hypothesized that there is similar up-regulation of D1R in a monogamous primate, the titi monkey ( Callicebus cupreus). Receptor binding of the D1R antagonist [11C]-SCH23390 was measured in male titi monkeys using PET scans before and after pairing with a female. We found that within-subject analyses of pairing show significant increases in D1R binding in the lateral septum, but not the nucleus accumbens, caudate, putamen, or ventral pallidum. The lateral septum is involved in a number of processes that may contribute to social behavior, including motivation, affect, reward, and reinforcement. This region also plays a role in pair bonding and paternal behavior in voles. Our observations of changes in D1R in the lateral septum, but not the nucleus accumbens, suggest that there may be broadly similar dopaminergic mechanisms underlying pair bonding across mammalian species, but that the specific changes to neural circuitry differ. This study is the first research to demonstrate neuroplasticity of the dopamine system following pair bonding in a non-human primate; however, substantial variability in the response to pairing suggests the utility of further research on the topic. [ABSTRACT FROM AUTHOR]

In a scintillation detector, the light generated in the scintillator by a gamma interaction is converted to photoelectrons by a photodetector and produces a time-dependent waveform, the shape of which depends on the scintillator properties and the photodetector response. Several depth-of-interaction (DOI) encoding strategies have been developed that manipulate the scintillator’s temporal response along the crystal length and therefore require pulse shape discrimination techniques to differentiate waveform shapes. In this work, we demonstrate how maximum likelihood (ML) estimation methods can be applied to pulse shape discrimination to better estimate deposited energy, DOI and interaction time (for time-of-flight (TOF) PET) of a gamma ray in a scintillation detector. We developed likelihood models based on either the estimated detection times of individual photoelectrons or the number of photoelectrons in discrete time bins, and applied to two phosphor-coated crystals (LFS and LYSO) used in a previously developed TOF-DOI detector concept. Compared with conventional analytical methods, ML pulse shape discrimination improved DOI encoding by 27% for both crystals. Using the ML DOI estimate, we were able to counter depth-dependent changes in light collection inherent to long scintillator crystals and recover the energy resolution measured with fixed depth irradiation (~11.5% for both crystals). Lastly, we demonstrated how the Richardson-Lucy algorithm, an iterative, ML-based deconvolution technique, can be applied to the digitized waveforms to deconvolve the photodetector’s single photoelectron response and produce waveforms with a faster rising edge. After deconvolution and applying DOI and time-walk corrections, we demonstrated a 13% improvement in coincidence timing resolution (from 290 to 254 ps) with the LFS crystal and an 8% improvement (323 to 297 ps) with the LYSO crystal. [ABSTRACT FROM PUBLISHER]

Background: Acute intoxication with organophosphorus (OP) cholinesterase inhibitors can trigger convulsions that progress to life-threatening status epilepticus. Survivors face long-term morbidity including mild-to-severe decline in memory. It is posited that neuroinflammation plays a key role in the pathogenesis of OP-induced neuropsychiatric deficits. Rigorous testing of this hypothesis requires preclinical models that recapitulate relevant phenotypic outcomes. Here, we describe a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP) that exhibits persistent neuroinflammation and cognitive impairment. Methods: Neuroinflammation, neurodegeneration, and cognitive function were compared in adult male Sprague Dawley rats injected with an acutely toxic dose of DFP vs. vehicle controls at multiple time points up to 36 days post-exposure. Neuroinflammation was quantified using immunohistochemical biomarkers of microglia (ionized calcium-binding adapter molecule 1, IBA1) and activated astrocytes (glial fibrillary acidic protein, GFAP) and positron emission tomography (PET) imaging of [11C]-(R)-PK11195, a ligand for the 18-kDa mitochondrial membrane translocator protein (TSPO). FluoroJade-B staining was used to assess neurodegeneration; Pavlovian conditioning, to assess cognitive function. Results: Animals exhibited moderate-to-severe seizures within minutes of DFP injection that continued for up to 6 h post-injection. As indicated by IBA1 and GFAP immunoreactivity and by PET imaging of TSPO, acute DFP intoxication triggered neuroinflammation in the hippocampus and cortex during the first 3 days that peaked at 7 days and persisted to 21 days post-exposure in most animals. Neurodegeneration was detected in multiple brain regions from 1 to 14 days post-exposure. All DFP-intoxicated animals exhibited significant deficits in contextual fear conditioning at 9 and 20 days post-exposure compared to vehicle controls. Whole-brain TSPO labeling positively correlated with seizure severity score, but did not correlate with performance in the contextual fear-conditioning task. Conclusions: We describe a preclinical model in which acute DFP intoxication causes seizures, persistent neuroinflammation, neurodegeneration, and memory impairment. The extent of the neuroinflammatory response is influenced by seizure severity. However, the observation that a subset of animals with moderate seizures and minimal TSPO labeling exhibited cognitive deficits comparable to those of animals with severe seizures and significant TSPO labeling suggests that DFP may impair learning and memory circuitry via mechanisms independent of seizures or neuroinflammation. [ABSTRACT FROM AUTHOR]

The performance of an 8 \times 8 array of 6.0 \times 6.0~\mm^2 (active area) SiPMs was evaluated for PET applications using crystal arrays with different pitch sizes (3.4, 1.5, 1.35, and 1.2 mm) and custom designed five-channel front-end readout electronics (four channels for position information and one channel for timing information). The total area of this SiPM array is 57.4 \times 57.4~\mm^2, and the pitch size is 7.2 mm. It was fabricated using enhanced blue sensitivity SiPMs (MicroFB-60035-SMT) with peak spectral sensitivity at 420 nm. The performance of the SiPM array was characterized by measuring flood histogram decoding quality, energy resolution, timing resolution and saturation at several bias voltages (from 25.0 to 30.0 V in 0.5 V intervals) and two different temperatures (5^\circ C and 20^\circC). Results show that the best flood histogram was obtained at a bias voltage of 28.0 V and 5^\circC and an array of polished LSO crystals with a pitch as small as 1.2 mm can be resolved. No saturation was observed up to a bias voltage of 29.5 V during the experiments, due to adequate light sharing between SiPMs. Energy resolution and timing resolution at 5^\circC ranged from 12.7 \pm 0.8\% to 14.6 \pm 1.4\% and 1.58 \pm 0.13~\ns to 2.50 \pm 0.44~\ns, for crystal array pitch sizes of 3.4 and 1.2 mm, respectively. Superior flood histogram quality, energy resolution and timing resolution were obtained with larger crystal array pitch sizes and at lower temperature. Based on our findings, we conclude that this large-area SiPM array can serve as a suitable photodetector for high-resolution small-animal PET or dedicated human brain PET scanners. [ABSTRACT FROM AUTHOR]

Purpose: In support of a project to build a total-body PET scanner with an axial field-of-view of 2 m, the authors are developing simple, cost-effective block detectors with combined time-of-flight (TOF) and depth-of-interaction (DOI) capabilities. Methods: This work focuses on investigating the potential of phosphor-coated crystals with conventional PMT-based block detector readout to provide DOI information while preserving timing resolution. The authors explored a variety of phosphor-coating configurations with single crystals and crystal arrays. Several pulse shape discrimination techniques were investigated, including decay time, delayed charge integration (DCI), and average signal shapes. Results: Pulse shape discrimination based on DCI provided the lowest DOI positioning error: 2 mm DOI positioning error was obtained with single phosphor-coated crystals while 3-3.5 mm DOI error was measured with the block detector module. Minimal timing resolution degradation was observed with single phosphor-coated crystals compared to uncoated crystals, and a timing resolution of 442 ps was obtained with phosphor-coated crystals in the block detector compared to 404 ps without phosphor coating. Flood maps showed a slight degradation in crystal resolvability with phosphor-coated crystals; however, all crystals could be resolved. Energy resolution was degraded by 3%-7% with phosphor-coated crystals compared to uncoated crystals. Conclusions: These results demonstrate the feasibility of obtaining TOF-DOI capabilities with simple block detector readout using phosphor-coated crystals. [ABSTRACT FROM AUTHOR]

Purpose: The MatrixSL-9-30035-OEM (Matrix9) from SensL is a large-area silicon photomultiplier (SiPM) photodetector module consisting of a 3 x 3 array of 4 x 4 element SiPM arrays (total of 144 SiPM pixels) and incorporates SensL's front-end electronics board and coincidence board. Each SiPM pixel measures 3.16 x 3.16 mm² and the total size of the detector head is 47.8 x 46.3 mm². Using 8 x 8 polished LSO/LYSO arrays (pitch 1.5 mm) the performance of this detector system (SiPM array and readout electronics) was evaluated with a view for its eventual use in small-animal positron emission tomography (PET). Methods: Measurements of noise, signal, signal-to-noise ratio, energy resolution, flood histogram quality, timing resolution, and array trigger error were obtained at different bias voltages (28.0-32.5 V in 0.5 V intervals) and at different temperatures (5 °C-25 °C in 5 °C degree steps) to find the optimal operating conditions. Results: The best measured signal-to-noise ratio and flood histogram quality for 511 keV gamma photons were obtained at a bias voltage of 30.0 V and a temperature of 5 °C. The energy resolution and timing resolution under these conditions were 14.2% ± 0.1% and 4.2 ± 0.1 ns, respectively. The flood histograms show that all the crystals in the 1.5 mm pitch LSO array can be clearly identified and that smaller crystal pitches can also be resolved. Flood histogram quality was also calculated using different center of gravity based positioning algorithms. Improved and more robust results were achieved using the local 9 pixels for positioning along with an energy offset calibration. To evaluate the front-end detector readout, and multiplexing efficiency, an array trigger error metric is introduced and measured at different lower energy thresholds. Using a lower energy threshold greater than 150 keV effectively eliminates any mispositioning between SiPM arrays. Conclusions: In summary, the Matrix9 detector system can resolve high-resolution scintillator arrays common in small-animal PET with adequate energy resolution and timing resolution over a large detector area. The modular design of the Matrix9 detector allows it to be used as a building block for simple, low channel-count, yet high performance, small animal PET or PET/MRI systems. [ABSTRACT FROM AUTHOR]

We present an analysis of the signal properties of a position-sensitive solid-state photomultiplier (PS-SSPM) that has an integrated resistive network for position sensing. Attractive features of PS-SSPMs are their large area and ability to resolve small scintillator crystals. However, the large area leads to a high detector capacitance, and in order to achieve high spatial resolution a large network resistor value is required. These inevitably create a low-pass filter that drastically slows what would be a fast micro-cell discharge pulse. Significant changes in the signal shape of the PS-SSPM cathode output as a function of position are observed, which result in a position-dependent time delay when using traditional time pick-off methods such as leading edge discrimination and constant fraction discrimination. The timing resolution and time delay, as a function of position, were characterized for two different PS-SSPM designs, a continuous 10~\mm \times 10~\mm PS-SSPM and a tiled 2 \times 2 array of 5~\mm \times 5~\mm PS-SSPMs. After time delay correction, the block timing resolution, measured with a 6 \times 6 array of 1.3 \times 1.3 \times 20~\mm^3 LSO crystals, was 8.6 ns and 8.5 ns, with the 10 mm PS-SSPM and 5 mm PS-SSPM respectively. The effect of crystal size on timing resolution was also studied, and contrary to expectation, a small improvement was measured when reducing the crystal size from 1.3 mm to 0.5 mm. Digital timing methods were studied and showed great promise for allowing accurate timing by implementation of a leading edge time pick-off. Position-dependent changes in signal shape on the anode side also are present, which complicates peak height data acquisition methods used for positioning. We studied the effect of trigger position on signal amplitude, flood histogram quality, and depth-of-interaction resolution in a dual-ended readout detector configuration. We conclude that detector timing and positioning can be significantly improved by implementation of digital timing methods and by accounting for changes in the shape of the signals from PS-SSPMs. [ABSTRACT FROM AUTHOR]