The CirPAD, a circular 1.4 M hybrid pixel detector dedicated to X-ray diffraction measurements at Synchrotron SOLEIL

One of the challenges of all synchrotron facilities is to offer the highest performance detectors for all their specific experiments, in particular for X-ray diffraction imaging and its high throughput data collection. In that context, the DiffAbs beamline, the Detectors and the Design and Engineering groups at Synchrotron SOLEIL, in collaboration with ImXPAD and Cegitek companies, have developed an original and unique detector with a circular shape. This detector is based on the hybrid pixel photon-counting technology and consists of the specific assembly of 20 hybrid pixel array detector (XPAD) modules. This article aims to demonstrate the main characteristics of the CirPAD (for Circular Pixel Array Detector) and its performance – i.e. excellent pixel quality, flat-field correction, high-count-rate performance, etc. Additionally, the powder X-ray diffraction pattern of an LaB6 reference sample is presented and refined. The obtained results demonstrate the high quality of the data recorded from the CirPAD, which allows the proposal of its use to all scientific communities interested in performing experiments at the DiffAbs beamline.

Design of MIRA, a low-noise pixelated ASIC for the readout of micro-channel plates

We present the design of the first prototype of MIRA (MIcro-channel plate Readout ASIC) that has been designed to read out Micro-Channel Plates (MCP), in particular for UV spectroscopy. MIRA will be able to detect the cloud of electrons generated by each photon interacting with the MCP, sustaining high local and global count rates to fully exploit the MCP intrinsic dynamic range with low dead time. The main rationale that guided the electronics design is the reduction of the input Equivalent Noise Charge (ENC) in order to allow operations with lower MCP gain, thus improving its lifetime, crucial aspect for long missions in space. MIRA features two selectable analog processing times, 133 ns or 280 ns (i.e. fast mode or slow mode), granting a count rate per pixel of 100 kcps. Moreover, it shows an Equivalent Noise Charge ENC = 17 e r m s − . A spatial resolution of 35 μm and an operation with zero dead time, due to the readout, are targeted. The low noise, high count rate and high spatial resolution requirements are expected by keeping a compact pixel size (35 μm × 35 μm) for a total of 32 × 32 pixels in a 2 mm × 2 mm ASIC area. In this work, the ASIC design is described.

Nearly Exact Discrepancy Principle for Low-Count Poisson Image Restoration

The effectiveness of variational methods for restoring images corrupted by Poisson noise strongly depends on the suitable selection of the regularization parameter balancing the effect of the regulation term(s) and the generalized Kullback–Liebler divergence data term. One of the approaches still commonly used today for choosing the parameter is the discrepancy principle proposed by Zanella et al. in a seminal work. It relies on imposing a value of the data term approximately equal to its expected value and works well for mid- and high-count Poisson noise corruptions. However, the series truncation approximation used in the theoretical derivation of the expected value leads to poor performance for low-count Poisson noise. In this paper, we highlight the theoretical limits of the approach and then propose a nearly exact version of it based on Monte Carlo simulation and weighted least-square fitting. Several numerical experiments are presented, proving beyond doubt that in the low-count Poisson regime, the proposed modified, nearly exact discrepancy principle performs far better than the original, approximated one by Zanella et al., whereas it works similarly or slightly better in the mid- and high-count regimes.

Understanding Monoclonal B Cell Lymphocytosis: An Interplay of Genetic and Microenvironmental Factors

The term monoclonal B-cell lymphocytosis (MBL) describes the presence of a clonal B cell population with a count of less than 5 × 109/L and no symptoms or signs of disease. Based on the B cell count, MBL is further classified into 2 distinct subtypes: ‘low-count’ and ‘high-count’ MBL. High-count MBL shares a series of biological and clinical features with chronic lymphocytic leukemia (CLL), at least of the indolent type, and evolves to CLL requiring treatment at a rate of 1-2% per year, whereas ‘low-count’ MBL seems to be distinct, likely representing an immunological rather than a pre-malignant condition. That notwithstanding, both subtypes of MBL can carry ‘CLL-specific’ genomic aberrations such as cytogenetic abnormalities and gene mutations, yet to a much lesser extent compared to CLL. These findings suggest that such aberrations are mostly relevant for disease progression rather than disease onset, indirectly pointing to microenvironmental drive as a key contributor to the emergence of MBL. Understanding microenvironmental interactions is therefore anticipated to elucidate MBL ontogeny and, most importantly, the relationship between MBL and CLL.

Quantitative SPECT (QSPECT) at high count rates with contemporary SPECT/CT systems

Background Accurate QSPECT is crucial in dosimetry-based, personalized radiopharmaceutical therapy with 177Lu and other radionuclides. We compared the quantitative performance of three NaI(Tl)-crystal SPECT/CT systems equipped with low-energy high-resolution collimators from two vendors (Siemens Symbia T6; GE Discovery 670 and NM/CT 870 DR). Methods Using up to 14 GBq of 99mTc in planar mode, we determined the calibration factor and dead-time constant under the assumption that these systems have a paralyzable behaviour. We monitored their response when one or both detectors were activated. QSPECT capability was validated by SPECT/CT imaging of a customized NEMA phantom containing up to 17 GBq of 99mTc. Acquisitions were reconstructed with a third-party ordered subset expectation maximization algorithm. Results The Siemens system had a higher calibration factor (100.0 cps/MBq) and a lower dead-time constant (0.49 μs) than those from GE (75.4–87.5 cps/MBq; 1.74 μs). Activities of up to 3.3 vs. 2.3–2.7 GBq, respectively, were quantifiable by QSPECT before the observed count rate plateaued or decreased. When used in single-detector mode, the QSPECT capability of the former system increased to 5.1 GBq, whereas that of the latter two systems remained independent of the detectors activation mode. Conclusion Despite similar hardware, SPECT/CT systems’ response can significantly differ at high count rate, which impacts their QSPECT capability in a post-therapeutic setting.

Increased Plasma Levels of lncRNAs LINC01268, GAS5 and MALAT1 Correlate with Negative Prognostic Factors in Myelofibrosis

Long non-coding RNAs (lncRNAs) have been recently described as key mediators in the development of hematological malignancies. In the last years, circulating lncRNAs have been proposed as a new class of non-invasive biomarkers for cancer diagnosis and prognosis and to predict treatment response. The present study is aimed to investigate the potential of circulating lncRNAs as non-invasive prognostic biomarkers in myelofibrosis (MF), the most severe among Philadelphia-negative myeloproliferative neoplasms. We detected increased levels of seven circulating lncRNAs in plasma samples of MF patients (n = 143), compared to healthy controls (n = 65). Among these, high levels of LINC01268, MALAT1 or GAS5 correlate with detrimental clinical variables, such as high count of leukocytes and CD34+ cells, severe grade of bone marrow fibrosis and presence of splenomegaly. Strikingly, high plasma levels of LINC01268 (p = 0.0018), GAS5 (p = 0.0008) or MALAT1 (p = 0.0348) are also associated with a poor overall-survival while high levels of LINC01268 correlate with a shorter leukemia-free-survival. Finally, multivariate analysis demonstrated that the plasma level of LINC01268 is an independent prognostic variable, suggesting that, if confirmed in future in an independent patients’ cohort, it could be used for further studies to design an updated classification model for MF patients.

Optimizing Urine Collection Represents an Important Stewardship Opportunity in Primary Care

Background: Urine cultures are the most common microbiological tests in the outpatient setting and heavily influence treatment of suspected urinary tract infections (UTIs). Antibiotics for UTI are usually prescribed on an empiric basis in primary care before the urine culture results are available. However, culture results may be needed to confirm a UTI diagnosis and to verify that the correct antibiotic was prescribed. Although urine cultures are considered as the gold standard for diagnosis of UTI, cultures can easily become contaminated during collection. We determined the prevalence, predictors, and antibiotic use associated with contaminated urine cultures in 2 adult safety net primary care clinics. Methods: We conducted a retrospective chart review of visits with provider-suspected UTI in which a urine culture was ordered (November 2018–March 2020). Patient demographics, culture results, and prescription orders were captured for each visit. Culture results were defined as no culture growth, contaminated (ie, mixed flora, non-uropathogens, or ≥3 bacteria isolated on culture), low-count positive (growth between 100 and 100,000 CFU/mL), and high-count positive (>100,000 CFU/mL). A multivariable multinomial logistic regression model was used to identify factors associated with contaminated culture results. Results: There were 1,265 visits with urine cultures: 264 (20.9%) had no growth, 694 (54.9%) were contaminated, 159 (12.6%) were low counts, and 148 (11.7%) were high counts. Encounter-level factors are presented in Table 1. Female gender (adjusted odds ratio [aOR], 15.8; 95% confidence interval [CI], 10.21–23.46; P < .001), pregnancy (aOR, 13.98; 95% CI, 7.93–4.67; P < .001), and obesity (aOR, 1.9; 95% CI 1.31–2.77; P < .001) were independently associated with contaminated cultures. Of 264 patients whose urine cultures showed no growth, 36 (14%) were prescribed an antibiotic. Of 694 patients with contaminated cultures, 153 (22%) were prescribed an antibiotic (Figure 1). Conclusions: More than half of urine cultures were contaminated, and 1 in 5 patients were treated with antibiotics. Reduction of contamination should improve patient care by providing a more accurate record of the organism in the urine (if any) and its susceptibilities, which are relevant to managing future episodes of UTI in that patient. Optimizing urine collection represents a diagnostic stewardship opportunity in primary care.Funding: This study was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (grant no. UM1AI104681). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Disclosures: None