Prevalence and classification of congenital thoracic vertebral body abnormalities in neurologically normal brachycephalic 'screw-tail' dog breeds in referral practice in Australia.

OBJECTIVE: To evaluate the prevalence, type, site and breed predisposition of thoracic congenital vertebral malformations (CVM) in neurologically normal brachycephalic 'screw-tail' dog breeds. STUDY DESIGN: Retrospective case series. ANIMALS: Neurologically normal French Bulldogs (n = 63), British Bulldogs (n = 42), Boston Terriers (n = 4) and Pugs (n = 86) presenting for brachycephalic obstructive airway syndrome treatment. METHODS: Either a plain computer tomography scan of the thorax or lateral and dorso-ventral digital radiographs of the thoracic vertebral column of each dog were assessed for any vertebral malformations and classed according to the Modified McMaster vertebral abnormality classification scheme proposed by Guiterrez et al. RESULTS: The prevalence of dogs with one or more abnormal vertebrae was 96.82% in French Bulldogs, 90.47% in British Bulldogs, and 76.74% in Pugs. Pugs had significantly lower instances of CVMs than French Bulldogs. The four Boston Terriers all had vertebral malformations, but the results were not considered to be statistically significant due to their small sample size. In French Bulldogs and British Bulldogs, ventral hypoplasia (Type 3) occurred at greater rates than all other types, followed by ventral and median hypoplasia (Types 7) and symmetrical hypoplasia (Type 8). In Pugs, symmetrical hypoplasia (Type 8) was the most common and then ventral hypoplasia (Type 3). The most affected vertebrae were T6-T9 in Pugs and T5-T10 in French Bulldogs and British Bulldogs. CONCLUSIONS: The majority of neurologically normal brachycephalic 'screw-tail' dogs assessed in this paper possessed one or more congenital thoracic vertebral malformations. Dogs with vertebral malformations were found to be more likely to have more than one affected vertebra. Sex had no effect on the prevalence of CVM. CLINICAL RELEVANCE: A substantial number of neurologically normal brachycephalic 'screw-tail' dogs suffer from congenital vertebral malformations. Thus, the need for selective breeding programmes to eliminate this hereditary condition is crucial.

SARS-CoV-2 seroprevalence in pregnant women in Kilifi, Kenya from March 2020 to March 2022.

Background: Seroprevalence studies are an alternative approach to estimating the extent of transmission of SARS-CoV-2 and the evolution of the pandemic in different geographical settings. We aimed to determine the SARS-CoV-2 seroprevalence from March 2020 to March 2022 in a rural and urban setting in Kilifi County, Kenya. Methods: We obtained representative random samples of stored serum from a pregnancy cohort study for the period March 2020 to March 2022 and tested for antibodies against the spike protein using a qualitative SARS-CoV-2 ELISA kit (Wantai, total antibodies). All positive samples were retested for anti-SARS-CoV-2 anti-nucleocapsid antibodies (Euroimmun, ELISA kits, NCP, qualitative, IgG) and anti-spike protein antibodies (Euroimmun, ELISA kits, QuantiVac; quantitative, IgG). Results: A total of 2,495 (of 4,703 available) samples were tested. There was an overall trend of increasing seropositivity from a low of 0% [95% CI 0-0.06] in March 2020 to a high of 89.4% [95% CI 83.36-93.82] in Feb 2022. Of the Wantai test-positive samples, 59.7% [95% CI 57.06-62.34] tested positive by the Euroimmun anti-SARS-CoV-2 NCP test and 37.4% [95% CI 34.83-40.04] tested positive by the Euroimmun anti-SARS-CoV-2 QuantiVac test. No differences were observed between the urban and rural hospital but villages adjacent to the major highway traversing the study area had a higher seroprevalence. Conclusion: Anti-SARS-CoV-2 seroprevalence rose rapidly, with most of the population exposed to SARS-CoV-2 within 23 months of the first cases. The high cumulative seroprevalence suggests greater population exposure to SARS-CoV-2 than that reported from surveillance data.

Agronomic biofortification increases grain zinc concentration of maize grown under contrasting soil types in Malawi.

Zinc (Zn) deficiency remains a public health problem in Malawi, especially among poor and marginalized rural populations, linked with low dietary intake of Zn due to consumption of staple foods that are low in Zn content. The concentration of Zn in staple cereal grain can be increased through application of Zn-enriched fertilizers, a process called agronomic biofortification or agro-fortification. Field experiments were conducted at three Agricultural Research Station sites to assess the potential of agronomic biofortification to improve Zn concentration in maize grain in Malawi as described in registered report published previously. The hypotheses of the study were (i) that application of Zn-enriched fertilizers would increase in the concentration of Zn in maize grain to benefit dietary requirements of Zn and (ii) that Zn concentration in maize grain and the effectiveness of agronomic biofortification would be different between soil types. At each site two different subsites were used, each corresponding to one of two agriculturally important soil types of Malawi, Lixisols and Vertisols. Within each subsite, three Zn fertilizer rates (1, 30, and 90 kg ha-1) were applied to experimental plots, using standard soil application methods, in a randomized complete block design. The experiment had 10 replicates at each of the three sites as informed by a power analysis from a pilot study, published in the registered report for this experiment, designed to detect a 10% increase in grain Zn concentration at 90 kg ha-1, relative to the concentration at 1 kg ha-1. At harvest, maize grain yield and Zn concentration in grain were measured, and Zn uptake by maize grain and Zn harvest index were calculated. At 30 kg ha-1, Zn fertilizer increased maize grain yields by 11% compared with nationally recommended application rate of 1 kg ha-1. Grain Zn concentration increased by 15% and uptake by 23% at the application rate of 30 kg ha-1 relative to the national recommendation rate. The effects of Zn fertilizer application rate on the response variables were not dependent on soil type. The current study demonstrates the importance of increasing the national recommendation rate of Zn fertilizer to improve maize yield and increase the Zn nutritional value of the staple crop.

Clinico-epidemiological profile and outcomes of adults with COVID-19: A hospital-based retrospective study in Kerala, India.

Introduction: The clinical and epidemiological presentations of patients with coronavirus disease 2019 (COVID-19) in India is still not well explored. We studied the epidemiological and clinical profile and outcomes of COVID-19 patients admitted to a tertiary care private hospital in Kerala, India. Methods: In this retrospective study, we analyzed data of 476 adult (≥18 years) COVID-19 patients admitted to a tertiary care hospital in Kerala from September 1, 2020 to March 31, 2021. The patients were categorized into mild, moderate, and severe cases and followed till discharge or death. Data were analyzed using Statistical Package for the Social Sciences (SPSS) version 23.0 with a significance set at P < 0.05. Results: The median age was 57 years (56% men). Mild, moderate, and severe cases accounted for 17%, 65%, and 18%, respectively. Around 75% had at least one comorbidity, and 51% had multiple comorbidities. The most common comorbidities were diabetes (45%), hypertension (44%), dyslipidemia (15%), and cardiac problems (12%). The elevated D-dimer values among patients in different categories were significantly different, with 74% in severe, 46% in moderate, and 19% in mild category patients. Serum ferritin, C-reactive protein, lactic acid dehydrogenase, and neutrophil to lymphocyte ratio values were significantly higher for severely ill patients. Thirty deaths (67% men) occurred during the study period, with a case fatality rate of 6.3%. Mortality mainly happened in the older age group (80%) and those with multimorbidity (90%). Conclusion: Age and multimorbidity are the major contributing factors for death in hospitalized COVID-19 patients. Generalization of the findings necessitates well-designed large-scale studies.

Piperaquine Exposure Is Altered by Pregnancy, HIV, and Nutritional Status in Ugandan Women.

Dihydroartemisinin-piperaquine (DHA-PQ) provides highly effective therapy and chemoprevention for malaria in pregnant African women. PQ concentrations of >10.3 ng/ml have been associated with reduced maternal parasitemia, placental malaria, and improved birth outcomes. We characterized the population pharmacokinetics (PK) of PQ in a post hoc analysis of human immunodeficiency virus (HIV)-infected and -uninfected pregnant women receiving DHA-PQ as chemoprevention every 4 or 8 weeks. The effects of covariates such as pregnancy, nutritional status (body mass index [BMI]), and efavirenz (EFV)-based antiretroviral therapy were investigated. PQ concentrations from two chemoprevention trials were pooled to create a population PK database from 274 women and 2,218 PK observations. A three-compartment model with an absorption lag best fit the data. Consistent with our prior intensive PK evaluation, pregnancy and EFV use resulted in a 72% and 61% increased PQ clearance, compared to postpartum and HIV-uninfected pregnant women, respectively. Low BMI at 28 weeks of gestation was associated with increased clearance (2% increase per unit decrease in BMI). Low-BMI women given DHA-PQ every 8 weeks had a higher prevalence of parasitemia, malaria infection, and placental malaria compared to women with higher BMIs. The reduced piperaquine exposure in women with low BMI as well as during EFV coadministration, compared to pregnant women with higher BMIs and not taking EFV, suggests that these populations could benefit from weekly instead of monthly dosing for prevention of malaria parasitemia. Simulations indicated that because of the BMI-clearance relationship, weight-based regimens would not improve protection compared to a 2,880 mg fixed-dose regimen when provided monthly. (The clinical trials described in this paper have been registered at ClinicalTrials.gov under identifiers NCT02163447 and NCT02282293.).

Increasing zinc concentration in maize grown under contrasting soil types in Malawi through agronomic biofortification: Trial protocol for a field experiment to detect small effect sizes.

The prevalence of micronutrient deficiencies including zinc (Zn) is widespread in Malawi, especially among poor and marginalized rural populations. This is due to low concentrations of Zn in most staple cereal crops and limited consumption of animal source foods. The Zn concentration of cereal grain can be increased through application of Zn-enriched fertilizers; a process termed agronomic biofortification or agro-fortification. This trial protocol describes a field experiment which aims to assess the potential of agronomic biofortification to improve the grain Zn concentration of maize, the predominant staple crop of Malawi. The hypotheses of the study are that application of Zn-enriched fertilizers will create a relatively small increase in the concentration of Zn in maize grains that will be sufficient to benefit dietary supplies of Zn, and that the effectiveness of agronomic biofortification will differ between soil types. The study will be conducted at three sites, Chitedze, Chitala, and Ngabu Agricultural Research Stations, in Lilongwe, Salima, and Chikwawa Districts respectively. These three sites represent locations in the Central and Southern Regions of Malawi. At each site, two different sub-sites will be used, each corresponding to one of two agriculturally important soil types of Malawi, Lixisols, and Vertisols. Within each sub-site, three Zn fertilizer rates (1, 30, and 90 kg/ha) will be applied to experimental plots using standard soil application methods, in a randomized complete block design. The number of replicates at plot level has been informed by a power analysis from pilot study data, assuming that a minimum 10% increase in Zn concentration of grain at 90 kg/ha relative to the concentration at 1 kg/ha is of interest. Grain mass (yield), stover mass, and both stover and grain Zn concentrations will be measured at harvest. A second year of cropping will be used to establish whether there are any residual benefits to grain Zn concentration. The potential for Zn agronomic biofortification will be communicated to relevant academic and government stakeholders through a peer review journal article and a briefing paper.

Increasing collaborative research output between early-career health researchers in Africa: lessons from the CARTA fellowship program.

In 2008 nine African Universities and four African research institutions, in partnership with non-African institutions started the Consortium for Advanced Research Training in Africa (CARTA) to strengthen doctoral training and research capacity on health in Africa. This study describes particular aspects of the CARTA program that promotes collaboration between the PhD fellows in the program, and determines the patterns of collaborative publications that resulted from the intervention. We reviewed program monitoring and evaluation documents and conducted a bibliometric analysis of 806 peer-reviewed publications by CARTA fellows published between 2011 and 2018. Results indicate that recruiting multidisciplinary fellows from various institutions, encouraging registration of doctoral-level fellows outside home institutions, and organizing joint research seminars stimulated collaborative research on health-related topics. Fellows collaborated among themselves and with non-CARTA researchers. Fellows co-authored 75 papers (10%) between themselves, of which 53 (71%) and 42 (56%) included fellows of different cohorts and different disciplines respectively, and 19 (25%) involved fellows of different institutions. CARTA graduates continued to publish with each other after graduating - 11% of the collaborative publications occurred post-graduation - indicating that the collaborative approach was maintained after exiting from the program. However, not all fellows contributed to publishing collaborative papers. The study recommends concerted effort towards enhancing collaborative publications among the CARTA fellows, both doctoral and post-doctoral, which can include holding research exchange forums and collaborative grant-writing workshops.

Efavirenz-Based Antiretroviral Therapy Reduces Artemether-Lumefantrine Exposure for Malaria Treatment in HIV-Infected Pregnant Women.

BACKGROUND: The choice of malaria treatment for HIV-infected pregnant women receiving efavirenz-based antiretroviral therapy must consider the potential impact of drug interactions on antimalarial exposure and clinical response. The aim of this study was to investigate the effects of efavirenz on artemether-lumefantrine (AL) because no studies have isolated the impact of efavirenz for HIV-infected pregnant women. METHODS: A prospective clinical pharmacokinetic (PK) study compared HIV-infected, efavirenz-treated pregnant women with HIV-uninfected pregnant women in Tororo, Uganda. All women received the standard 6-dose AL treatment regimen for Plasmodium falciparum malaria with intensive PK samples collected over 21 days and 42-days of clinical follow-up. PK exposure parameters were calculated for artemether, its active metabolite dihydroartemisinin (DHA), and lumefantrine to determine the impact of efavirenz. RESULTS: Nine HIV-infected and 30 HIV-uninfected pregnant women completed intensive PK evaluations. Relative to controls, concomitant efavirenz therapy lowered the 8-hour artemether concentration by 76% (P = 0.013), DHA peak concentration by 46% (P = 0.033), and day 7 and 14 lumefantrine concentration by 61% and 81% (P = 0.046 and 0.023), respectively. In addition, there were nonsignificant reductions in DHA area under the concentration-time curve0-8hr (35%, P = 0.057) and lumefantrine area under the concentration-time curve0-∞ (34%, P = 0.063) with efavirenz therapy. CONCLUSIONS: Pregnant HIV-infected women receiving efavirenz-based antiretroviral therapy during malaria treatment with AL showed reduced exposure to both the artemisinin and lumefantrine. These data suggest that malaria and HIV coinfected pregnant women may require adjustments in AL dosage or treatment duration to achieve exposure comparable with HIV-uninfected pregnant women.

An Evaluation of a Train-the-Trainer Workshop for Social Service Workers to Develop Community-Based Family Interventions.

INTRODUCTION: Evaluation studies on train-the-trainer workshops (TTTs) to develop family well-being interventions are limited in the literature. The Logic Model offers a framework to place some important concepts and tools of intervention science in the hands of frontline service providers. This paper reports on the evaluation of a TTT for a large community-based program to enhance family well-being in Hong Kong. METHODS: The 2-day TTT introduced positive psychology themes (relevant to the programs that the trainees would deliver) and the Logic Model (which provides a framework to guide intervention development and evaluation) for social service workers to guide their community-based family interventions. The effectiveness of the TTT was examined by self-administered questionnaires that assessed trainees' changes in learning (perceived knowledge, self-efficacy, attitude, and intention), trainees' reactions to training content, knowledge sharing, and benefits to their service organizations before and after the training and then 6 months and 1 year later. Missing data were replaced by baseline values in an intention-to-treat analysis. Focus group interviews were conducted approximately 6 months after training. RESULTS: Fifty-six trainees (79% women) joined the TTT. Forty-four and 31 trainees completed the 6-month and 1-year questionnaires, respectively. The trainees indicated that the workshop was informative and well organized. The TTT-enhanced trainees' perceived knowledge, self-efficacy, and attitudes toward the application of the Logic Model and positive psychology constructs in program design. These changes were present with small to large effect size that persisted to the 1 year follow-up. The skills learned were used to develop 31 family interventions that were delivered to about 1,000 families. Qualitative feedback supported the quantitative results. CONCLUSION: This TTT offers a practical example of academic-community partnerships that promote capacity among community social service workers. Goals included sharing basic tools of intervention development and evaluation, and the TTT offered, therefore, the potential of learning skills that extended beyond the lifetime of a single program. CLINICAL TRIAL REGISTRATION: The research protocol was registered at the National Institutes of Health (identifier number: NCT01796275).

Development and Two-Year Follow-Up Evaluation of a Training Workshop for the Large Preventive Positive Psychology Happy Family Kitchen Project in Hong Kong.

Evidence-based practice and capacity-building approaches are essential for large-scale health promotion interventions. However, there are few models in the literature to guide and evaluate training of social service workers in community settings. This paper presents the development and evaluation of the "train-the-trainer" workshop (TTT) for the first large scale, community-based, family intervention projects, entitled "Happy Family Kitchen Project" (HFK) under the FAMILY project, a Hong Kong Jockey Club Initiative for a Harmonious Society. The workshop aimed to enhance social workers' competence and performance in applying positive psychology constructs in their family interventions under HFK to improve family well-being of the community they served. The two-day TTT was developed and implemented by a multidisciplinary team in partnership with community agencies to 50 social workers (64% women). It focused on the enhancement of knowledge, attitude, and practice of five specific positive psychology themes, which were the basis for the subsequent development of the 23 family interventions for 1419 participants. Acceptability and applicability were enhanced by completing a needs assessment prior to the training. The TTT was evaluated by trainees' reactions to the training content and design, changes in learners (trainees) and benefits to the service organizations. Focus group interviews to evaluate the workshop at three months after the training, and questionnaire survey at pre-training, immediately after, six months, one year and two years after training were conducted. There were statistically significant increases with large to moderate effect size in perceived knowledge, self-efficacy and practice after training, which sustained to 2-year follow-up. Furthermore, there were statistically significant improvements in family communication and well-being of the participants in the HFK interventions they implemented after training. This paper offers a practical example of development, implementation and model-based evaluation of training programs, which may be helpful to others seeking to develop such programs in diverse communities.

Artemether-Lumefantrine Pharmacokinetics and Clinical Response Are Minimally Altered in Pregnant Ugandan Women Treated for Uncomplicated Falciparum Malaria.

Artemether-lumefantrine is a first-line regimen for the treatment of uncomplicated malaria during the second and third trimesters of pregnancy. Previous studies have reported changes in the pharmacokinetics and clinical outcomes following treatment with artemether-lumefantrine in pregnant women compared to nonpregnant adults; however, the results are inconclusive. We conducted a study in rural Uganda to compare the pharmacokinetics of artemether-lumefantrine and the treatment responses between 30 pregnant women and 30 nonpregnant adults with uncomplicated Plasmodium falciparum malaria. All participants were uninfected with HIV, treated with a six-dose regimen of artemether-lumefantrine, and monitored clinically for 42 days. The pharmacokinetics of artemether, its metabolite dihydroartemisinin, and lumefantrine were evaluated for 21 days following treatment. We found no significant differences in the overall pharmacokinetics of artemether, dihydroartemisinin, or lumefantrine in a direct comparison of pregnant women to nonpregnant adults, except for a statistically significant but small difference in the terminal elimination half-lives of both dihydroartemisinin and lumefantrine. There were seven PCR-confirmed reinfections (5 pregnant and 2 nonpregnant participants). The observation of a shorter terminal half-life for lumefantrine may have contributed to a higher frequency of reinfection or a shorter posttreatment prophylactic period in pregnant women than in nonpregnant adults. While the comparable overall pharmacokinetic exposure is reassuring, studies are needed to further optimize antimalarial efficacy in pregnant women, particularly in high-transmission settings and because of emerging drug resistance. (This study is registered at ClinicalTrials.gov under registration no. NCT01717885.).

Performance of the Tachyon Time-of-Flight PET Camera.

We have constructed and characterized a time-of-flight Positron Emission Tomography (TOF PET) camera called the Tachyon. The Tachyon is a single-ring Lutetium Oxyorthosilicate (LSO) based camera designed to obtain significantly better timing resolution than the ~ 550 ps found in present commercial TOF cameras, in order to quantify the benefit of improved TOF resolution for clinically relevant tasks. The Tachyon's detector module is optimized for timing by coupling the 6.15 × 25 mm2 side of 6.15 × 6.15 × 25 mm3 LSO scintillator crystals onto a 1-inch diameter Hamamatsu R-9800 PMT with a super-bialkali photocathode. We characterized the camera according to the NEMA NU 2-2012 standard, measuring the energy resolution, timing resolution, spatial resolution, noise equivalent count rates and sensitivity. The Tachyon achieved a coincidence timing resolution of 314 ps +/- ps FWHM over all crystal-crystal combinations. Experiments were performed with the NEMA body phantom to assess the imaging performance improvement over non-TOF PET. The results show that at a matched contrast, incorporating 314 ps TOF reduces the standard deviation of the contrast by a factor of about 2.3.

A front-end readout Detector Board for the OpenPET electronics system.

We present a 16-channel front-end readout board for the OpenPET electronics system. A major task in developing a nuclear medical imaging system, such as a positron emission computed tomograph (PET) or a single-photon emission computed tomograph (SPECT), is the electronics system. While there are a wide variety of detector and camera design concepts, the relatively simple nature of the acquired data allows for a common set of electronics requirements that can be met by a flexible, scalable, and high-performance OpenPET electronics system. The analog signals from the different types of detectors used in medical imaging share similar characteristics, which allows for a common analog signal processing. The OpenPET electronics processes the analog signals with Detector Boards. Here we report on the development of a 16-channel Detector Board. Each signal is digitized by a continuously sampled analog-to-digital converter (ADC), which is processed by a field programmable gate array (FPGA) to extract pulse height information. A leading edge discriminator creates a timing edge that is "time stamped" by a time-to-digital converter (TDC) implemented inside the FPGA. This digital information from each channel is sent to an FPGA that services 16 analog channels, and then information from multiple channels is processed by this FPGA to perform logic for crystal lookup, DOI calculation, calibration, etc.

A New Time Calibration Method for Switched-capacitor-array-based Waveform Samplers.

We have developed a new time calibration method for the DRS4 waveform sampler that enables us to precisely measure the non-uniform sampling interval inherent in the switched-capacitor cells of the DRS4. The method uses the proportionality between the differential amplitude and sampling interval of adjacent switched-capacitor cells responding to a sawtooth-shape pulse. In the experiment, a sawtooth-shape pulse with a 40 ns period generated by a Tektronix AWG7102 is fed to a DRS4 evaluation board for calibrating the sampling intervals of all 1024 cells individually. The electronic time resolution of the DRS4 evaluation board with the new time calibration is measured to be ~2.4 ps RMS by using two simultaneous Gaussian pulses with 2.35 ns full-width at half-maximum and applying a Gaussian fit. The time resolution dependencies on the time difference with the new time calibration are measured and compared to results obtained by another method. The new method could be applicable for other switched-capacitor-array technology-based waveform samplers for precise time calibration.

Artifacts in digital coincidence timing.

Digital methods are becoming increasingly popular for measuring time differences, and are the de facto standard in PET cameras. These methods usually include a master system clock and a (digital) arrival time estimate for each detector that is obtained by comparing the detector output signal to some reference portion of this clock (such as the rising edge). Time differences between detector signals are then obtained by subtracting the digitized estimates from a detector pair. A number of different methods can be used to generate the digitized arrival time of the detector output, such as sending a discriminator output into a time to digital converter (TDC) or digitizing the waveform and applying a more sophisticated algorithm to extract a timing estimator.All measurement methods are subject to error, and one generally wants to minimize these errors and so optimize the timing resolution. A common method for optimizing timing methods is to measure the coincidence timing resolution between two timing signals whose time difference should be constant (such as detecting gammas from positron annihilation) and selecting the method that minimizes the width of the distribution (i.e. the timing resolution). Unfortunately, a common form of error (a nonlinear transfer function) leads to artifacts that artificially narrow this resolution, which can lead to erroneous selection of the 'optimal' method. The purpose of this note is to demonstrate the origin of this artifact and suggest that caution should be used when optimizing time digitization systems solely on timing resolution minimization.

MODELING TIME DISPERSION DUE TO OPTICAL PATH LENGTH DIFFERENCES IN SCINTILLATION DETECTORS.

We characterize the nature of the time dispersion in scintillation detectors caused by path length differences of the scintillation photons as they travel from their generation point to the photodetector. Using Monte Carlo simulation, we find that the initial portion of the distribution (which is the only portion that affects the timing resolution) can usually be modeled by an exponential decay. The peak amplitude and decay time depend both on the geometry of the crystal, the position within the crystal that the scintillation light originates from, and the surface finish. In a rectangular parallelpiped LSO crystal with 3 mm × 3 mm cross section and polished surfaces, the decay time ranges from 10 ps (for interactions 1 mm from the photodetector) up to 80 ps (for interactions 50 mm from the photodetector). Over that same range of distances, the peak amplitude ranges from 100% (defined as the peak amplitude for interactions 1 mm from the photodetector) down to 4% for interactions 50 mm from the photodetector. Higher values for the decay time are obtained for rough surfaces, but the exact value depends on the simulation details. Estimates for the decay time and peak amplitude can be made for different cross section sizes via simple scaling arguments.

Evaluation of the Timing Properties of a High Quantum Efficiency Photomultiplier Tube.

We measured the timing resolution of 189 R9800-100 photomultiplier tubes (PMTs), which are a SBA (Super Bialkali, high quantum efficiency) variant of the R9800 high-performance PMT manufactured by Hamamatsu Photonics, and correlated their timing resolutions with various measures of PMT performance, namely Cathode Luminous Sensitivity (CLS), Anode Luminous Sensitivity (ALS), Gain times Collection Efficiency (GCE), Cathode Blue Sensitivity Index (CBSI), Anode Blue Sensitivity Index (ABSI) and dark current. The correlation results show: (1) strong correlations between timing resolution and ALS, ABSI, and GCE; (2) moderate correlations between timing resolution and CBSI; and (3) weak or no correlations between timing resolution and dark current and CLS. The results disclosed that all three measures that include data collected from the anode (ALS, ABSI, and GCE) affect the timing resolution more than either of the two measures that only include photocathode data (CBSI and CLS). We conclude that: (1) the photocathode Quantum Efficiency (QE) and the product of the Gain and the Collection Efficiency (GCE) are the two dominant factors that affect the timing resolution, (2) the GCE variation affects the timing resolution more than the QE variation in the R9800 PMT, and (3) the performance depends on photocathode position.

High-performance electronics for time-of-flight PET systems.

We have designed and built a high-performance readout electronics system for time-of-flight positron emission tomography (TOF PET) cameras. The electronics architecture is based on the electronics for a commercial whole-body PET camera (Siemens/CPS Cardinal electronics), modified to improve the timing performance. The fundamental contributions in the electronics that can limit the timing resolution include the constant fraction discriminator (CFD), which converts the analog electrical signal from the photo-detector to a digital signal whose leading edge is time-correlated with the input signal, and the time-to-digital converter (TDC), which provides a time stamp for the CFD output. Coincident events are identified by digitally comparing the values of the time stamps. In the Cardinal electronics, the front-end processing electronics are performed by an Analog subsection board, which has two application-specific integrated circuits (ASICs), each servicing a PET block detector module. The ASIC has a built-in CFD and TDC. We found that a significant degradation in the timing resolution comes from the ASIC's CFD and TDC. Therefore, we have designed and built an improved Analog subsection board that replaces the ASIC's CFD and TDC with a high-performance CFD (made with discrete components) and TDC (using the CERN high-performance TDC ASIC). The improved Analog subsection board is used in a custom single-ring LSO-based TOF PET camera. The electronics system achieves a timing resolution of 60 ps FWHM. Prototype TOF detector modules are read out with the electronics system and give coincidence timing resolutions of 259 ps FWHM and 156 ps FWHM for detector modules coupled to LSO and LaBr3 crystals respectively.

Real-time quantitative ex vivo direct autoradiography with 10 µm pixel resolution.

We present three new autoradiography methods to map positron emission rate of a bio-specimen slice with high resolution. One is based on LBNL scientific charge coupled device (CCD) and the other two are based on conventional CCDs. High conversion efficiency (100k e-h pairs / 0.5 MeV positron) and low dark current (1.75 × 10(-4) e-/pix/sec) can be achieved using the LBNL CCD. The theoretical calculations and preliminary experiments show that an 86 µm spatial resolution can be achieved when imaging a 100 µm thick tissue soaked with (18)F which produce higher energy positron. The main disadvantage of the LBNL CCD we tested is that a very low operating temperature is required to eliminate dark current. This dramatically increases the system cost. In addition, the integration time of the CCD needs to be short enough to avoid overlapping of the positron trajectories. Conventional CCDs have lower conversion efficiency (2k e-h pairs / 0.5 MeV positron) and higher dark current (200 e-/pix/sec), but are more cost-efficient and the requirement for the readout frequency is much lower. The conversion efficiency of the conventional CCD imager can be improved by 17 times by inserting a 100 µm layer of phosphor between the sample and the imager. However, the light emitted from the phosphor screen will be ~100 µm diameter, which severely degrades the spatial resolution. A high readout frequency is also required to avoid the overlapping. The CCD systems designed in this study will be used to map positron emission rate of bio-specimens such as cancerous tissues acquired in regular biopsy procedure. They can also be used to corroborate tracer kinetic modeling at a cellular level.

A Design of a PET Detector Using Micro-Channel Plate Photomultipliers with Transmission-Line Readout.

A computer simulation study has been conducted to investigate the feasibility of a positron emission tomography (PET) detector design by using micro-channel plate (MCP) photomultiplier tubes (PMT) with transmission-line (TL) read-out and waveform sampling. The detector unit consisted of a 24×24 array of pixelated LSO crystals, each of which was 4×4×25 mm(3) in size, and two 102×102 mm(2) MCP-PMTs coupled to both sides of the scintillator array. The crystal (and TL) pitch was 4.25 mm and reflective medium was inserted between the crystals. The transport of the optical photons inside the scintillator were simulated by using the Geant4 package. The output pulses of the MCP-PMT/TL unit were formed by applying the measured single photo-electron response of the MCP-PMT/TL unit to each individual photon that interacts with the photo-cathode of the MCP-PMT. The waveforms of the pulses at both ends of the TL strips were measured and analyzed to produce energy and timing information for the detected event. An experimental setup was developed by employing a Photonis Planacon MCP-PMT (XP85022) and a prototype TL board for measuring the single photo-electron response of the MCP-PMT/TL. The simulation was validated by comparing the predicted output pulses to measurements obtained with a single MCP-PMT/TL coupled to an LSO crystal exposed to 511 keV gamma rays. The validated simulation was then used to investigate the performance of the proposed new detector design. Our simulation result indicates an energy resolution of ~11% at 511 keV. When using a 400-600 keV energy window, we obtain a coincidence timing resolution of ~323 ps FWHM and a coincidence detection efficiency of ~40% for normally-incident 511keV photons. For the positioning accuracy, it is determined by the pitch of the TLs (and crystals) in the direction normal to the TLs and measured to be ~2.5 mm in the direction parallel to the TLs. The energy and timing obtained at the front- and back-end of the scintillator array also show differences that are correlated with the depth of interaction of the event.