Timing and Energy Resolution of new near-UV SiPMs coupled to LaBr3:Ce for TOF-PET.

The high light output and fast decay time of LaBr3:Ce scintillation detectors leads to excellent timing performance. To realize the potential of timing resolution with LaBr3:Ce we have investigated the performance with SiPMs, which enable 1-to-1 coupling to individual crystals, and which have been optimized for the near-ultraviolet (NUV) scintillation light emission of LaBr3:Ce. Coincidence timing resolution (CTR) of 100 ps was measured for a 4×4×5 mm3 LaBr3:30%Ce crystal directly coupled to a large-area 4×4 mm2 NUV-SiPM. Results show very little dependence on temperature, in the range of -20° to 20°C, and bias voltage, from 2 V to 5 V over breakdown. Optimal performance was achieved at an over-voltage (OV) range of 3 V - 5 V, at which high gain and high photon detection efficiency are achieved. Though saturation was evident at 511 keV, an energy resolution of 6.8% was measured after correcting for non-linearity. We also measured a CTR of 110 ps for a 4×4×5mm3 LaBr3:5%Ce crystal and 245 ps for a 4×4×30 mm3 LaBr3:5%Ce crystal using the NUV-SIPM. The poorer timing measurement for the 30-mm long crystal is due mainly to a systematic shift in the time pick-off as a function of the depth-of-interaction. The excellent temperature stability, fast rise time, high gain, and low noise of the NUV-SiPM make it a practical and highly appealing photodetector for the readout of a LaBr3:Ce TOF-PET detector.

A Decision Support System for Diabetes Chronic Care Models Based on General Practitioner Engagement and EHR Data Sharing.

Objective Decision support systems (DSS) have been developed and promoted for their potential to improve quality of health care. However, there is a lack of common clinical strategy and a poor management of clinical resources and erroneous implementation of preventive medicine. Methods To overcome this problem, this work proposed an integrated system that relies on the creation and sharing of a database extracted from GPs' Electronic Health Records (EHRs) within the Netmedica Italian (NMI) cloud infrastructure. Although the proposed system is a pilot application specifically tailored for improving the chronic Type 2 Diabetes (T2D) care it could be easily targeted to effectively manage different chronic-diseases. The proposed DSS is based on EHR structure used by GPs in their daily activities following the most updated guidelines in data protection and sharing. The DSS is equipped with a Machine Learning (ML) method for analyzing the shared EHRs and thus tackling the high variability of EHRs. A novel set of T2D care-quality indicators are used specifically to determine the economic incentives and the T2D features are presented as predictors of the proposed ML approach. Results The EHRs from 41237 T2D patients were analyzed. No additional data collection, with respect to the standard clinical practice, was required. The DSS exhibited competitive performance (up to an overall accuracy of 98%±2% and macro-recall of 96%±1%) for classifying chronic care quality across the different follow-up phases. The chronic care quality model brought to a significant increase (up to 12%) of the T2D patients without complications. For GPs who agreed to use the proposed system, there was an economic incentive. A further bonus was assigned when performance targets are achieved. Conclusions The quality care evaluation in a clinical use-case scenario demonstrated how the empowerment of the GPs through the use of the platform (integrating the proposed DSS), along with the economic incentives, may speed up the improvement of care.

Performance of a high-resolution depth-encoding PET detector module using linearly-graded SiPM arrays.

The goal of this study was to exploit the excellent spatial resolution characteristics of a position-sensitive silicon photomultiplier (SiPM) and develop a high-resolution depth-of-interaction (DOI) encoding positron emission tomography (PET) detector module. The detector consists of a 30 × 30 array of 0.445 × 0.445 × 20 mm3 polished LYSO crystals coupled to two 15.5 × 15.5 mm2 linearly-graded SiPM (LG-SiPM) arrays at both ends. The flood histograms show that all the crystals in the LYSO array can be resolved. The energy resolution, the coincidence timing resolution and the DOI resolution were 21.8 ± 5.8%, 1.23 ± 0.10 ns and 3.8 ± 1.2 mm, respectively, at a temperature of -10 °C and a bias voltage of 35.0 V. The performance did not degrade significantly for event rates of up to 130 000 counts s-1. This detector represents an attractive option for small-bore PET scanner designs that simultaneously emphasize high spatial resolution and high detection efficiency, important, for example, in preclinical imaging of the rodent brain with neuroreceptor ligands.

The Sulfate Supply Maximizing Arabidopsis Shoot Growth Is Higher under Long- than Short-Term Exposure to Cadmium.

The processes involved in cadmium detoxification in plants deeply affect sulfate uptake and thiol homeostasis and generate increases in the plant nutritional request for sulfur. Here, we present an analysis of the dependence of Arabidopsis growth on the concentration of sulfate in the growing medium with the aim of providing evidence on how plants optimize growth at a given sulfate availability. Results revealed that short-term (72 h) exposure to a broad range of Cd concentrations (0.1, 1, and 10 µM) inhibited plant growth but did not produce any significant effects on the growth pattern of both shoots and roots in relation to the external sulfate. Conversely, long-term (22 days) exposure to 0.1 µM Cd significantly changed the pattern of fresh weight accumulation of the shoots in relation to the external sulfate, without affecting that of the roots, although their growth was severely inhibited by Cd. Moreover, under long-term exposure to Cd, increasing the sulfate external concentration up to the critical value progressively reduced the inhibitory effects exerted by Cd on shoot growth, indicating the existence of sulfate-dependent adaptive responses protecting the shoot tissues against Cd injury. Transcriptional induction of the high-affinity sulfate transporter genes (SULTR1; 1 and SULTR1; 2) involved in sulfate uptake by roots was a common adaptive response to both short- and long-term exposure to Cd. Such a response was closely related to the total amount of non-protein thiols accumulated by a single plant under short-term exposure to Cd, but did not showed any clear relation with thiols under long-term exposure to Cd. In this last condition, Cd exposure did not change the level of non-protein thiols per plant and thus did not alter the nutritional need for sulfur. In conclusion, our results indicate that long term-exposure to Cd, although it induces sulfate uptake, decreases the capacity of the Arabidopsis roots to efficiently absorb the sulfate ions available in the growing medium making the adaptive response of SULTR1; 1 and SULTR1; 2 "per se" not enough to optimize the growth at sulfate external concentrations lower than the critical value.

Bismuth germanate coupled to near ultraviolet silicon photomultipliers for time-of-flight PET.

Bismuth germanate (BGO) was a very attractive scintillator in early-generation positron emission tomography (PET) scanners. However, the major disadvantages of BGO are lower light yield and longer rise and decay time compared to currently popular scintillators such as LSO and LYSO. This results in poorer coincidence timing resolution and it has generally been assumed that BGO is not a suitable scintillator for time-of-flight (TOF) PET applications. However, when a 511 keV photon interacts in a scintillator, a number of Cerenkov photons are produced promptly by energetic electrons released by photoelectric or Compton interactions. If these prompt photons can be captured, they could provide a better timing trigger for PET. Since BGO has a high refractive index (increasing the Cerenkov light yield) and excellent optical transparency down to 320 nm (Cerenkov light yield is higher at shorter wavelengths), we hypothesized that the coincidence timing resolution of BGO can be significantly improved by efficient detection of the Cerenkov photons. However, since the number of Cerenkov photons is far less than the number of scintillation photons, and they are more abundant in the UV and blue part of the spectrum, photosensors need to have high UV/blue sensitivity, fast temporal response, and very low noise in order to trigger on the faint Cerenkov signal. In this respect, NUV-HD silicon photomultipliers (SiPMs) (FBK, Trento, Italy) are an excellent fit for our approach. In this study, coincidence events were measured using BGO crystals coupled with NUV-HD SiPMs. The existence and influence of Cerenkov photons on the timing measurements were studied using different configurations to exploit the directionality of the Cerenkov emissions. Coincidence resolving time values (FWHM) of ~270 ps from 2 × 3 × 2 mm3 BGO crystals and ~560 ps from 3 × 3 × 20 mm3 BGO crystals were obtained. To our knowledge, these are the best coincidence resolving time values reported for BGO to date. With these values, BGO can be considered as a relevant scintillator for TOF PET scanners, especially if photodetectors with even better near UV/blue response can be developed to further improve the efficiency of Cerenkov light detection.

Reaching 200-ps timing resolution in a time-of-flight and depth-of-interaction positron emission tomography detector using phosphor-coated crystals and high-density silicon photomultipliers.

Current research in the field of positron emission tomography (PET) focuses on improving the sensitivity of the scanner with thicker detectors, extended axial field-of-view, and time-of-flight (TOF) capability. These create the need for depth-of-interaction (DOI) encoding to correct parallax errors. We have proposed a method to encode DOI using phosphor-coated crystals. Our initial work using photomultiplier tubes (PMTs) demonstrated the possibilities of the proposed method, however, a major limitation of PMTs for this application is poor quantum efficiency in yellow light, corresponding to the wavelengths of the converted light by the phosphor coating. In contrast, the red-green-blue-high-density (RGB-HD) silicon photomultipliers (SiPMs) have a high photon detection efficiency across the visible spectrum. Excellent coincidence resolving time (CRT; [Formula: see text]) was obtained by coupling RGB-HD SiPMs and [Formula: see text] lutetium fine silicate crystals coated on a third of one of their lateral sides. Events were classified in three DOI bins ([Formula: see text] width) with an average sensitivity of 83.1%. A CRT of [Formula: see text] combined with robust DOI encoding is a marked improvement in the phosphor-coated approach that we pioneered. For the first time, we read out these crystals with SiPMs and clearly demonstrated the potential of the RGB-HD SiPMs for this TOF-DOI PET detector.

Kinetic Analysis of Zinc/Cadmium Reciprocal Competitions Suggests a Possible Zn-Insensitive Pathway for Root-to-Shoot Cadmium Translocation in Rice.

BACKGROUND: Among cereals, rice has a genetic propensity to accumulate high levels of cadmium (Cd) in grains. Xylem-mediated root-to-shoot translocation rather than root uptake has been suggested as the main physiological factor accounting for the genotypic variation observed in Cd accumulation in shoots and grains. Several evidence indicate OsHMA2 - a putative zinc (Zn) transporter - as the main candidate protein that could be involved in mediating Cd- and Zn-xylem loading in rice. However, the specific interactions between Zn and Cd in rice often appear anomalous if compared to those observed in other staple crops, suggesting that root-to-shoot Cd translocation process could be more complex than previously thought. In this study we performed a complete set of competition experiments with Zn and Cd in order to analyze their possible interactions and reciprocal effects at the root-to-shoot translocation level. RESULTS: The competition analysis revealed the lack of a full reciprocity when considering the effect of Cd on Zn accumulation, and vice versa, since the accumulation of Zn in the shoots was progressively inhibited by Cd increases, whereas that of Cd was only partially impaired by Zn. Such behaviors were probably dependent on Cd-xylem loading mechanisms, as suggested by: i) the analysis of Zn and Cd content in the xylem sap performed in relation to the concentration of the two metals in the mobile fractions of the roots; ii) the analysis of the systemic movement of (107)Cd in short term experiments performed using a positron-emitting tracer imaging system (PETIS). CONCLUSIONS: Our results suggest that at least two pathways may mediate root-to-shoot Cd translocation in rice. The former could involve OsHMA2 as Zn(2+)/Cd(2+) xylem loader, whereas the latter appears to involve a Zn-insensitive system that still needs to be identified.

Sub-100 ps coincidence time resolution for positron emission tomography with LSO:Ce codoped with Ca.

The coincidence time resolution (CTR) becomes a key parameter of 511 keV gamma detection in time of flight positron emission tomography (TOF-PET). This is because additional information obtained through timing leads to a better noise suppression and therefore a better signal to noise ratio in the reconstructed image. In this paper we present the results of CTR measurements on two different SiPM technologies from FBK coupled to LSO:Ce codoped 0.4%Ca crystals. We compare the measurements performed at two separate test setups, i.e. at CERN and at FBK, showing that the obtained results agree within a few percent. We achieve a best CTR value of 85 ± 4 ps FWHM for 2 × 2 × 3 mm(3) LSO:Ce codoped 0.4%Ca crystals, thus breaking the 100 ps barrier with scintillators similar to LSO:Ce or LYSO:Ce. We also demonstrate that a CTR of 140 ± 5 ps can be achieved for longer 2 × 2 × 20 mm(3) crystals, which can readily be implemented in the current generation PET systems to achieve the desired increase in the signal to noise ratio.

SPAD aptasensor for the detection of circulating protein biomarkers.

The need for decentralized clinical tests together with the concept of time and cost saving are pushing the development of portable, miniaturized, compact biosensors with diagnostic and prognostic purpose. Here, we propose an innovative detection system based on a Single Photon Avalanche Diode (SPAD) with high sensitivity and low noise, crucial features for an efficient chemiluminescence biosensor. The SPAD detector, having 60 µm diameter, has a Photon Detection Efficiency higher than 55% at 425 nm and a Dark Count Rate lower than 100 Hz at room temperature. Our design allows a good optical coupling efficiency between sample and detector. A specific biofunctional surface was implemented taking advantage of aptamers, short DNA sequences having high selectivity and affinity toward their targets. We successfully detected physiological levels of Vascular Endothelial Growth Factor (VEGF), a circulating protein biomarker highly correlated with cancer. The SPAD aptasensor showed a Limit of Detection (LoD) in the pM range, stability (up to 42 days) and re-usability (up to seven cycles). This compact biosensor is therefore a promising step toward the actual use of portable microdevices in diagnostics.

SiPM optical crosstalk amplification due to scintillator crystal: effects on timing performance.

For a given photon detection efficiency (PDE), the primary, Poisson distributed, dark count rate of the detector (DCR0) is one of the most limiting factors affecting the timing resolution of a silicon photomultiplier (SiPM) in the scintillation light readout. If the effects of DCR0 are removed through a suitable baseline compensation algorithm or by cooling, it is possible to clearly observe another phenomenon that limits the PDE, and thus the timing resolution of the detector. It is caused by the optical crosstalk of the SiPM, which is significantly increased by the presence of the scintillator. In this paper, we describe this phenomenon, which is also easily observed from the reverse I-V curve of the device, and we relate it to the measured coincidence resolving time in 511 keV γ-ray measurements. We discuss its consequences on the SiPM design and, in particular, we observe that there is an optimal cell size, dependent on both SiPM and crystal parameters, that maximizes the PDE in presence of optical crosstalk. Finally, we report on a crosstalk simulator developed to study the phenomenon and we compare the simulation results obtained for different SiPM technologies, featuring different approaches to the reduction of the crosstalk.

Performance of FBK high-density SiPM technology coupled to Ce:LYSO and Ce:GAGG for TOF-PET.

This paper presents the performance, in terms of energy and timing resolution, of high-density silicon photomultipliers (SiPMs) produced at Fondazione Bruno Kessler for time-of-flight positron emission tomography application. The new SiPM technology allows us to produce devices with a small cell size maintaining a high fill factor (FF). The sensors considered in this paper are composed by 30 × 30 µm(2) cells with a FF exceeding 70% to cover a total area of 4 × 4 mm(2). The SiPM performance was evaluated using two types of scintillators (Ce:LYSO and Ce:GaGG) both with a short height (5 mm) in order to minimize the time jitter caused by light propagation in the crystal. With Ce:LYSO, an energy resolution of 9.0% FWHM at 511 keV and a coincidence resolving time (CRT) of 125 ps FWHM were obtained at -20 °C. With Ce:GaGG, an energy resolution of 6.4% FWHM and a CRT of 260 ps FWHM were achieved at the same temperature. The novel SiPM technology, combining a high PDE with a low correlated noise (i.e., crosstalk and afterpulse), allows us to improve the state-of-the-art of energy and timing resolution with both the tested crystals.

Voice quality monitoring: a portable device prototype.

This paper addresses the important issue of voice monitoring throughout the day under a clinical perspective. This problem is of great concern, for rehabilitation and from the assistive technology point of view. A prototype for a new portable device is proposed, implementing basic voice quality indexes (fundamental frequency F0, jitter, relative average perturbation RAP, noise) by means of robust high-resolution techniques. The device is contact-less, as the transducer is a small microphone included in the device. A feedback for patients outside the clinic is provided, given by a led/audio unit that advices the patient for any abnormal vocal emission, to help patients with carryover of therapy goals outside the clinical environment. The device will collect audio recordings to be submitted to a PC for further analysis, to be performed off-line. Such device for self-diagnosis and vocal rehabilitation could give a valid support, both to clinicians and patients.