Terry Jones

Background: The Omnipod® 5 Automated Insulin Delivery (AID) System was shown to be safe and effective following 3 months of use in people with type 1 diabetes (T1D); however, data on the durability of these results are limited. This study evaluated the long-term safety and effectiveness of Omnipod 5 use in people with T1D during up to 2 years of use. Materials and Methods: After a 3-month single-arm, multicenter, pivotal trial in children (6–13.9 years) and adolescents/adults (14–70 years), participants could continue system use in an extension phase. HbA1c was measured every 3 months for up to 15 months; continuous glucose monitor metrics were collected for up to 2 years. Results: Participants (N = 224) completed median (interquartile range) 22.3 (21.7, 22.7) months of AID. HbA1c was reduced in the pivotal trial from 7.7% ± 0.9% in children and 7.2% ± 0.9% in adolescents/adults to 7.0% ± 0.6 …

P298Introduction: The goal of the NeuroEXPLORER (NX) project is to develop a next-generation dedicated brain PET system. Motivated by human brain HRRT studies (Yale) and total-body uEXPLORER studies (UC Davis), the NX design focused on ultra-high sensitivity and resolution, with continuous head motion correction. The NX has a cylindrical design with a system diameter of 52.4 cm and long axial field-of-view (FOV) of 49.5 cm. The detector micro-block consists of a 4x2 array of 1.56x3.07x20 mm LYSO crystals decoded by 4 3-mm SiPMs including depth-of-interaction (DOI) measurement using an optical bridge for light-sharing between axial crystal pairs. Performance tests (presented in another abstract) show time-of-flight (TOF) resolution of 236 psec, sensitivity of 46.8 kcps/MBq (NEMA), and point source (0 and 10-cm offset) transverse resolution of 1.8-2.2 mm with FBP and <1.4 mm with OSEM. The goal …

The TORCH detector aims to provide K/π (K/p) separation up to a momentum of about 10 (15) by measuring their time-of-flight at the LHCb detector. Prompt Cherenkov photons are produced in a quartz radiator bar of 10 mm thickness, and propagated via total internal reflection to the periphery of the detector, where they are focused onto an array of microchannel plate photomultipliers that measure the photon arrival time and position. Pattern recognition techniques are used to compare the likelihood that the detector image is due to a given particle hypothesis. Good performance is obtained even for very high detector occupancies.

High-voltage CMOS detectors are being developed for application in High-Energy Physics. ATLASPIX3 is a full-reticle size monolithic pixel detector, consisting of 49000 pixels of dimension 50×150 μm. It has been realized in in TSI 180 nm HVCMOS technology. In view of applications at future electron-positron colliders, multi-chip-modules are built. The module design and its characterization by electrical test and radiation sources will be illustrated, including characterization of shunt regulators for serial chain powering. Lightweight long structure to support and to cool multiple-module chain are also being realized. The multi-chip-modules performance shows no degradation with respect to single-chip devices and the level of integration achieved is suitable for tracking at future e+e- accelerators.

P720Introduction: The lungs are supplied by two blood vessels, the pulmonary arteries carrying deoxygenated blood originating from the right ventricle (RV) and the bronchial arteries carrying oxygenated blood from the left ventricle (LV). While the blood supply of normal lung tissue is usually dominated by the pulmonary artery, lung tumors tend to have an increased blood supply from the LV. However, this dual-blood supply effect has never been observed using PET, partially due to the limited temporal resolution of dynamic scans on conventional PET scanners. The advent of total-body PET allows high-temporal resolution (HTR) dynamic imaging. In this study, we proposed the dual-blood input function (DBIF) method for lung kinetic modeling using HTR dynamic imaging on the uEXPLORER total-body PET system and evaluated the impact of DBIF on the kinetic quantification of lung tumors.Methods: The study …

The world’s first total-body PET/CT system has been in routine clinical and research use at UC Davis since 2019. The uEXPLORER total-body PET scanner has been designed with an axial field-of-view long enough to completely encompass most human subjects (194 cm or 76 inches long), allowing for a 15–68-fold gain in the PET signal collection efficiency over conventional PET scanners. A high-sensitivity PET scanner that can image the entire subject with a single bed position comes with new benefits and challenges to consider for efficient and practical use. In this chapter, we discuss the common clinical and research imaging protocols implemented at our institution, along with the appropriate technical and practical considerations of total-body PET imaging.

Tracer kinetic modeling in dynamic PET has the potential to improve the diagnosis, prognosis, and research of lung diseases. The advent of total-body PET systems with much greater detection sensitivity enables high-temporal-resolution (HTR) dynamic PET imaging of the lungs. However, existing models may become insufficient for modeling the HTR data. In this paper, we investigate the necessity of additional corrections to the input function for HTR lung kinetic modeling. Methods: Dynamic scans with HTR frames of as short as 1 s were performed on 13 healthy subjects with a bolus injection of about of 18F-FDG using the uEXPLORER total-body PET/CT system. Three kinetic models with and without time-delay and dispersion corrections were compared for the quality of lung time–activity curve fitting using the Akaike information criterion. The impact on quantification of 18F-FDG delivery rate , net influx rate and fractional blood volume was …

TORCH is a large-area and high-precision time-of-flight detector, designed to provide charged particle identification over a 2–20 GeV/c momentum range. The TORCH detector comprises a 10 mm thick quartz radiator, instrumented with photon detectors, which precisely time and measure the arrival positions of the Cherenkov photons. The photon detectors are micro-channel plate photo-multiplier tubes (MCP-PMTs) comprising a finely segmented anode of 64× 64 anode pads, electronically ganged into 64× 8 pixels, over a 53× 53 mm 2 area, an excellent intrinsic time resolution of∼ 30 ps, and a long lifetime of up to≳ 5 C/cm 2. The current version of the MCP-PMTs used by TORCH have been developed with an industrial partner, Photek Ltd, to satisfy the stringent requirements of the detector. The TORCH R&D programme has successfully demonstrated the detector concept through extensive laboratory and beam …

Conventional whole-body static 18F-FDG PET imaging provides a semiquantitative evaluation of overall glucose metabolism without insight into the specific transport and metabolic steps. Here we demonstrate the ability of total-body multiparametric 18F-FDG PET to quantitatively evaluate glucose metabolism using macroparametric quantification and assess specific glucose delivery and phosphorylation processes using microparametric quantification for studying recovery from coronavirus disease 2019 (COVID-19). Methods: The study included 13 healthy subjects and 12 recovering COVID-19 subjects within 8 wk of confirmed diagnosis. Each subject had a 1-h dynamic 18F-FDG scan on the uEXPLORER total-body PET/CT system. Semiquantitative SUV and the SUV ratio relative to blood (SUVR) were calculated for different organs to measure glucose utilization. Tracer kinetic modeling was performed to quantify the microparametric blood-to …

BackgroundLow-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group.MethodsThis randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation< 92% on room air) were randomly allocated (1: 1) to either usual care with higher dose corticosteroids (dexamethasone 20 mg once daily for 5 days followed by 10 mg dexamethasone once daily for 5 days or until discharge if sooner) or usual standard of care alone …

Computing platforms that package multiple types of memory, each with their own performance characteristics, are quickly becoming mainstream. To operate efficiently, heterogeneous memory architectures require new data management solutions that are able to match the needs of each application with an appropriate type of memory. As the primary generators of memory usage, applications create a great deal of information that can be useful for guiding memory tiering, but the community still lacks tools to collect, organize, and leverage this information effectively. To address this gap, this work introduces a novel software framework that collects and analyzes object-level information to guide memory tiering. Using this framework, this study evaluates and compares the impact of a variety of data tiering choices, including how the system prioritizes objects for faster memory as well as the frequency and timing of …

BackgroundHospital transmission of SARS-CoV-2 has proved difficult to control, with healthcare-associated infections troublesome throughout.AimTo understand factors contributing to hospital transmission of infections, which is necessary for containing spread.MethodsAn outbreak of 56 staff and patient cases of COVID-19 over a 31-day period in a tertiary referral unit is presented, with at least a further 29 cases identified outside of the unit and the hospital by whole genome sequencing (WGS).FindingsTransmission is documented from staff to staff, staff to patients, and patients to staff, showing disruption of a tertiary referral service, despite implementation of nationally recommended control measures, superior ventilation, and use of personal protective equipment. There was extensive spread from the index case, despite this patient spending only 10 h bed bound on the ward in strict cubicle isolation and with an …

Many High Performance Computing (HPC) facilities have developed and deployed frameworks in support of continuous monitoring and operational data analytics (MODA) to help improve efficiency and throughput. Because of the complexity and scale of systems and workflows and the need for low-latency response to address dynamic circumstances, automated feedback and response have the potential to be more effective than current human-in-the-loop approaches which are laborious and error prone. Progress has been limited, however, by factors such as the lack of infrastructure and feedback hooks, and successful deployment is often site- and case-specific. In this position paper we report on the outcomes and plans from a recent Dagstuhl Seminar, seeking to carve a path for community progress in the development of autonomous feedback loops for MODA, based on the established formalism of similar …

TORCH is a novel time-of-flight detector, designed to provide charged particle identification of pions, kaons and protons in the momentum range 2–20 GeV/c over a 9.5 m flight path. A detector module, comprising a 10 mm thick quartz plate, provides a source of Cherenkov photons which propagate via total internal reflection to one end of the plate. Here, the photons are focused onto an array of custom-designed Micro-Channel Plate Photo-Multiplier Tubes (MCP-PMTs) which measure their positions and arrival times. The target time resolution per photon is 70 ps which, for 30 detected photons per charged particle, results in a 10–15 ps time-of-flight resolution. A 1.25 m length TORCH prototype module employing two MCP-PMTs has been developed, and tested at the CERN PS using a charged hadron beam of 8 GeV/c momentum. The construction of the module, the properties of the MCP-PMTs and the readout …

P801Introduction: We (Yale, UC Davis, United Imaging) have successfully developed NeuroEXPLORER (NX), a dedicated human brain PET/CT imager with high spatial resolution, high sensitivity, and continuous head motion correction. The extended axial field of view and a partial 6th detector ring with shoulder-cutout enhances sensitivity enabling image-derived input function from the carotid arteries. Here we present a detailed physical characterization and performance evaluation of this scanner based on NEMA NU 2-2018.Methods: The NX consists of 20 detector modules forming a cylindrical detector ring with a diameter and axial length of 52.4 cm and 49.5 cm, respectively. A novel U-shaped light-sharing detector array enables single-ended DOI encoding in addition to high spatial resolution and good TOF capability. Each U-shaped element consists of two 1.56×3.07×20.0 mm LYSO crystals and four U …

Background. Androgen deprivation therapy (ADT) for prostate cancer is implicated as a possible cause of cognitive impairment (CI). CI in dementia and Alzheimer’s disease is associated with neuroinflammation. In this study, we investigated a potential role of neuroinflammation in ADT-related CI. Methods. Patients with prostate cancer on ADT for ≥3 months were categorized as having ADT-emergent CI or normal cognition (NC) based on self-report at interview. Neuroinflammation was evaluated using positron emission tomography (PET) with the translocator protein (TSPO) radioligand [11C]-PBR28. [11C]-PBR28 uptake in various brain regions was quantified as standardized uptake value (SUVR, normalized to cerebellum) and related to blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) choice-reaction time task (CRT) activation maps. Results. Eleven patients underwent PET: four with reported CI (rCI), six with reported NC (rNC), and one status unrecorded. PET did not reveal any between-group differences in SUVR regionally or globally. There was no difference between groups on brain activation to the CRT. Regardless of the reported cognitive status, there was strong correlation between PET-TSPO signal and CRT activation in the hippocampus, amygdala, and medial cortex. Conclusions. We found no difference in neuroinflammation measured by PET-TSPO between patients with rCI and rNC. However, we speculate that the strong correlation between TSPO uptake and BOLD-fMRI activation in brain regions involved in memory and known to have high androgen-receptor expression mediating plasticity …

TORCH is a large-area time-of-flight (ToF) detector, proposed for the Upgrade-II of the LHCb experiment. It will provide charged hadron identification over a 2–20 GeV/c momentum range, given a 9.5 m flight distance from the LHC interaction point. To achieve this level of performance, a 15 ps timing resolution per track is required. A TORCH prototype module having a 1250× 660× 10 mm 3 fused-silica radiator plate and equipped with two MCP-PMTs has been tested in a 8 GeV/c CERN test-beam. Single-photon time resolutions of between 70–100 ps have been achieved, dependent on the beam position in the radiator. The measured photon yields agree with expectations.

P736Introduction: Clinical whole-body PET imaging is commonly performed with static scanning. The measured signal is normally a mix of radiotracer activities in multiple compartments. For example, for 18F-FDG, the signal mixes the free-state 18F-FDG and metabolized 18F-FDG-6P. Total-body PET empowers simultaneous dynamic imaging of the entire body. Here we explore the ability of total-body dynamic PET in combination with compartmental modeling to visualize the radiotracer activity in each individual compartment over time. We have demonstrated, for the first time, the derivation of quantitative images of metabolized 18F-FDG-6P and free-state 18F-FDG.Methods: Nine patients with metastatic genitourinary cancer were scanned with 353±18 MBq 18F-FDG on the uEXPLORER total-body PET/CT system for one hour. The acquired dynamic images were analyzed using a voxel-wise compartmental …

With most of the T cells residing in the tissue, not the blood, developing noninvasive methods for in vivo quantification of their biodistribution and kinetics is important for studying their role in immune response and memory. This study presents the first use of dynamic positron emission tomography (PET) and kinetic modeling for in vivo measurement of CD8+ T cell biodistribution in humans. A 89Zr-labeled CD8-targeted minibody (89Zr-Df-Crefmirlimab) was used with total-body PET in healthy individuals (N = 3) and coronavirus disease 2019 (COVID-19) convalescent patients (N = 5). Kinetic modeling results aligned with T cell–trafficking effects expected in lymphoid organs. Tissue-to-blood ratios from the first 7 hours of imaging were higher in bone marrow of COVID-19 convalescent patients compared to controls, with an increasing trend between 2 and 6 months after infection, consistent with modeled net influx rates …

Positron emission tomography (PET) is the most sensitive in vivo molecular imaging technique available. Small animal PET has been widely used in studying pharmaceutical biodistribution and disease progression over time by imaging a wide range of biological processes. However, it remains true that almost all small animal PET studies using mouse or rat as preclinical models are either limited by the spatial resolution or the sensitivity (especially for dynamic studies), or both, reducing the quantitative accuracy and quantitative precision of the results. Total-body small animal PET scanners, which have axial lengths longer than the nose-to-anus length of the mouse/rat and can provide high sensitivity across the entire body of mouse/rat, can realize new opportunities for small animal PET. This article aims to discuss the technical opportunities and challenges in developing total-body small animal PET scanners for …