Non-Invasive In Vivo Imaging of Calcium Signaling in Mice

Rapid and transient elevations of Ca2+ within cellular microdomains play a critical role in the regulation of many signal transduction pathways. Described here is a genetic approach for non-invasive detection of localized Ca2+ concentration ([Ca2+]) rises in live animals using bioluminescence imaging (BLI). Transgenic mice conditionally expressing the Ca2+-sensitive bioluminescent reporter GFP-aequorin targeted to the mitochondrial matrix were studied in several experimental paradigms. Rapid [Ca2+] rises inside the mitochondrial matrix could be readily detected during single-twitch muscle contractions. Whole body patterns of [Ca2+] were monitored in freely moving mice and during epileptic seizures. Furthermore, variations in mitochondrial [Ca2+] correlated to behavioral components of the sleep/wake cycle were observed during prolonged whole body recordings of newborn mice. This non-invasive imaging technique opens new avenues for the analysis of Ca2+ signaling whenever whole body information in freely moving animals is desired, in particular during behavioral and developmental studies

Application of Silicon Photomultipliers to Positron Emission Tomography

Historically, positron emission tomography (PET) systems have been based on scintillation crystals coupled to photomultipliers tubes (PMTs). However, the limited quantum efficiency, bulkiness, and relatively high cost per unit surface area of PMTs, along with the growth of new applications for PET, offers opportunities for other photodetectors. Among these, small-animal scanners, hybrid PET/MRI systems, and incorporation of time-of-flight information are of particular interest and require low-cost, compact, fast, and magnetic field compatible photodetectors. With high quantum efficiency and compact structure, avalanche photodiodes (APDs) overcome several of the drawbacks of PMTs, but this is offset by degraded signal-to-noise and timing properties. Silicon photomultipliers (SiPMs) offer an alternative solution, combining many of the advantages of PMTs and APDs. They have high gain, excellent timing properties and are insensitive to magnetic fields. At the present time, SiPM technology is rapidly developing and therefore an investigation into optimal design and operating conditions is underway together with detailed characterization of SiPM-based PET detectors. Published data are extremely promising and show good energy and timing resolution, as well as the ability to decode small scintillator arrays. SiPMs clearly have the potential to be the photodetector of choice for some, or even perhaps most, PET systems

Integration of polarization in the LUTDavis model for optical Monte Carlo simulation in radiation detectors

ObjectiveCerenkov photons have distinctive features from scintillation photons. Among them is their polarization: their electric field is always perpendicular to the direction of propagation of light and parallel to the plane of incidence. Scintillation photons are instead considered unpolarized.ApproachThis study aims at understanding and optimizing the reflectance of polarized Cerenkov photons for optical Monte Carlo simulation of scintillation detectors with Geant4/GATE. First, the Cerenkov emission spectrum and polarization were implemented in the previously developed look-up-table Davis model of crystal reflectance. Next, we modified Geant4/GATE source code to account for scintillation and Cerenkov photons LUTs simultaneously. Then, we performed optical Monte Carlo simulations in BGO using GATE to show the effect of Cerenkov features on the photons' momentum at the photodetector face, using two surface finishes, with and without reflector.Main resultsIn this work, we describe the new features added to the algorithm and GATE. We showed that Cerenkov characteristics affect their probability to be reflected/refracted and thus their travel path within a material.SignificanceWe showed the importance of accounting for accurate Cerenkov photons reflectance while performing advanced optical Monte Carlo simulations

DataSheet1_Effect of crystal-photodetector interface extraction efficiency on Cerenkov photons’ detection time.docx

Using Cerenkov photons to improve detector timing resolution in time-of-flight positron emission tomography scanners is promising since they constitute most of the signal rising edge. The main challenge in using Cerenkov light is its low yield per photoelectric interaction, which requires optimizing their complex optical transport in the detector. Monte Carlo simulations unlock information unavailable through benchtop measurements and help better understand the Cerenkov photon behavior. Although the first Cerenkov photons are emitted forward, part of the early triggering signal is lost due to poor light extraction at the crystal-photodetector interface. In addition, the electron path in the crystal, that determines the Cerenkov photon direction, is tortuous due to multiple scattering, causing the Cerenkov photons emitted after a few scatters to no longer be forward-directed. In this context, the transit time spread in the crystal, highly dependent on the detector geometry, plays a crucial role in the photon detection time. In this work, we performed optical simulations in bismuth germanium oxide using 511 keV gamma with GATE to investigate the optical photons extraction when modifying the index of refraction at the crystal-photodetector interface and the crystal aspect ratio. The mean detection time of the first, second, and third detected optical and Cerenkov photon separately was studied as a function of the total number of Cerenkov detected per event. For each configuration, we calculated the expected mean detection time using the probability of detection. Thinner crystals led to lower expected detection times due to the reduced transit time in the crystal. Reducing the refractive index discontinuity at the crystal-photodetector interface decreased all configurations expected mean detection time values. We showed that it not only improves the optical photons (scintillation and Cerenkov) detection efficiency at the photodetector face but directly ameliorates the probability of detecting the fastest one, reducing the effect of thicker materials and of losing the first detected photon information, both crucial to reduce the detector timing resolution. Thanks to their prompt emission and directionality at emission, Cerenkov photons represent the first detected optical photon in most configurations but increasing their detection efficiency is crucial to detect the fastest one.</p

DataSheet3_Effect of crystal-photodetector interface extraction efficiency on Cerenkov photons’ detection time.docx

Using Cerenkov photons to improve detector timing resolution in time-of-flight positron emission tomography scanners is promising since they constitute most of the signal rising edge. The main challenge in using Cerenkov light is its low yield per photoelectric interaction, which requires optimizing their complex optical transport in the detector. Monte Carlo simulations unlock information unavailable through benchtop measurements and help better understand the Cerenkov photon behavior. Although the first Cerenkov photons are emitted forward, part of the early triggering signal is lost due to poor light extraction at the crystal-photodetector interface. In addition, the electron path in the crystal, that determines the Cerenkov photon direction, is tortuous due to multiple scattering, causing the Cerenkov photons emitted after a few scatters to no longer be forward-directed. In this context, the transit time spread in the crystal, highly dependent on the detector geometry, plays a crucial role in the photon detection time. In this work, we performed optical simulations in bismuth germanium oxide using 511 keV gamma with GATE to investigate the optical photons extraction when modifying the index of refraction at the crystal-photodetector interface and the crystal aspect ratio. The mean detection time of the first, second, and third detected optical and Cerenkov photon separately was studied as a function of the total number of Cerenkov detected per event. For each configuration, we calculated the expected mean detection time using the probability of detection. Thinner crystals led to lower expected detection times due to the reduced transit time in the crystal. Reducing the refractive index discontinuity at the crystal-photodetector interface decreased all configurations expected mean detection time values. We showed that it not only improves the optical photons (scintillation and Cerenkov) detection efficiency at the photodetector face but directly ameliorates the probability of detecting the fastest one, reducing the effect of thicker materials and of losing the first detected photon information, both crucial to reduce the detector timing resolution. Thanks to their prompt emission and directionality at emission, Cerenkov photons represent the first detected optical photon in most configurations but increasing their detection efficiency is crucial to detect the fastest one.</p

A generative adversarial network to speed up optical Monte Carlo simulations

Detailed simulation of optical photon transport and detection in radiation detectors is often used for crystal-based gamma detector optimization. However, the time and memory burden associated with the track-wise approach to particle transport and detection in commonly used Monte Carlo codes makes optical simulation prohibitive at a system level, where hundreds to thousands of scintillators must be modeled. Consequently, current large system simulations do not include detailed detector models to analyze the potential performance gain with new radiation detector technologies. Generative adversarial networks (GANs) are explored as a tool to speed up the optical simulation of crystal-based detectors. These networks learn training datasets made of high-dimensional data distributions. Once trained, the resulting model can produce distributions belonging to the training data probability distribution. In this work, we present the proof of concept of using a GAN to enable high-fidelity optical simulations of nuclear medicine systems, mitigating their computational complexity. The architecture of the first network version and high-fidelity training dataset is discussed. The latter is generated through accurate optical simulation with GATE/Geant4, and contains the position, direction, and energy distributions of the optical photons emitted by 511 keV gamma rays in bismuth germanate and detected on the photodetector face. We compare the GAN and simulation-generated distributions in terms of similarity using the Jensen–Shannon distance. Excellent agreement was found with similarity values higher than 93.5% for all distributions. Moreover, the GAN speeded the optical photon distribution generation by up to two orders of magnitude. These very promising results have the potential to drastically change the use of nuclear imaging system optical simulations by enabling high-fidelity system-level simulations in reasonable computation times. The ultimate is to integrate the GAN within GATE/Geant4 since numerous applications (large detectors, bright scintillators, Cerenkov-based timing positron emission tomography) can benefit from these improvements

DataSheet5_Effect of crystal-photodetector interface extraction efficiency on Cerenkov photons’ detection time.docx

Using Cerenkov photons to improve detector timing resolution in time-of-flight positron emission tomography scanners is promising since they constitute most of the signal rising edge. The main challenge in using Cerenkov light is its low yield per photoelectric interaction, which requires optimizing their complex optical transport in the detector. Monte Carlo simulations unlock information unavailable through benchtop measurements and help better understand the Cerenkov photon behavior. Although the first Cerenkov photons are emitted forward, part of the early triggering signal is lost due to poor light extraction at the crystal-photodetector interface. In addition, the electron path in the crystal, that determines the Cerenkov photon direction, is tortuous due to multiple scattering, causing the Cerenkov photons emitted after a few scatters to no longer be forward-directed. In this context, the transit time spread in the crystal, highly dependent on the detector geometry, plays a crucial role in the photon detection time. In this work, we performed optical simulations in bismuth germanium oxide using 511 keV gamma with GATE to investigate the optical photons extraction when modifying the index of refraction at the crystal-photodetector interface and the crystal aspect ratio. The mean detection time of the first, second, and third detected optical and Cerenkov photon separately was studied as a function of the total number of Cerenkov detected per event. For each configuration, we calculated the expected mean detection time using the probability of detection. Thinner crystals led to lower expected detection times due to the reduced transit time in the crystal. Reducing the refractive index discontinuity at the crystal-photodetector interface decreased all configurations expected mean detection time values. We showed that it not only improves the optical photons (scintillation and Cerenkov) detection efficiency at the photodetector face but directly ameliorates the probability of detecting the fastest one, reducing the effect of thicker materials and of losing the first detected photon information, both crucial to reduce the detector timing resolution. Thanks to their prompt emission and directionality at emission, Cerenkov photons represent the first detected optical photon in most configurations but increasing their detection efficiency is crucial to detect the fastest one.</p