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Time‐of‐flight (TOF) technique, traditionally used in high energy physics (HEP) and positron emission tomography (PET), is now being explored for lower energy applications like computed tomography (CT). Regardless of the application, pushing the current boundaries in time resolution calls for novel technologies and materials exhibiting ultra‐fast time response. Semiconductor nanocrystals like cesium lead halide perovskites (CsPbBr3), benefiting from quantum confinement effects, feature ultra‐fast decay and, when combined with a suitable bulk scintillator following a heterostructure concept, can also provide the necessary stopping power. In this work, thin films of CsPbBr3 on top of BGO, LYSO:Ce, and GAGG:Ce,Mg wafers are fabricated to test their impact on the single crystal scintillator time resolution under soft X‐rays excitation (about 10 keV). It is demonstrated that the CsPbBr3 layer significantly improves the overall time resolution in all cases, achieving up to a tenfold improvement with BGO and GAGG:Ce,Mg. Under 511 keV γ‐rays, a proof‐of‐concept of the heterostructure design for TOF‐PET using CsPbBr3 thin film deposited on GAGG:Ce,Mg bulk crystal is successfully tested. Shared events depositing energy in both materials are identified, resulting in more than twofold improved coincidence time resolution: 118 ± 4 ps full‐width‐at‐half‐maximum (FWHM) compared to the 272 ± 8 ps of solely GAGG:Ce,Mg. Cesium lead bromide thin films were deposited on GAGG, BGO, and LYSO to improve their timing performances. The time resolution of the resulting heterostructures was measured under X‐ray and 511 keV γ‐ray irradiation, achieving tenfold and twofold improvement over the standard scintillator in the two measurements respectively. This demonstrates great potential for time‐of‐flight X‐ray (TOF‐X‐ray) and positron emission tomography (TOF‐PET) applications.

Light Detection and Ranging (LiDAR) is a 3D imaging technique, widely used in many applications such as augmented reality, automotive, machine vision, spacecraft navigation and landing. Achieving long-ranges and high-speed, most of all in outdoor applications with strong solar background illumination, are challenging requirements. In the introduction we review different 3D-ranging techniques (stereo-vision, projection with structured light, pulsed-LiDAR, amplitude-modulated continuous-wave LiDAR, frequency-modulated continuous-wave interferometry), illumination schemes (single point and blade scanning, flash-LiDAR) and time-resolved detectors for LiDAR (EM-CCD, I-CCD, APD, SPAD, SiPM). Then, we provide an extensive review of silicon- single photon avalanche diode (SPAD)-based LiDAR detectors (both commercial products and research prototypes) analyzing how each architecture faces the main challenges of LiDAR (i.e., long ranges, centimeter resolution, large field-of-view and high angular resolution, high operation speed, background immunity, eye-safety and multi-camera operation). Recent progresses in 3D stacking technologies provided an important step forward in SPAD array development, allowing to reach smaller pitch, higher pixel count and more complex processing electronics. In the conclusions, we provide some guidelines for the design of next generation SPAD-LiDAR detectors.

A novel method for (ultra-)high-resolution spatial mass separation in time-of-flight mass spectrometers is presented. Ions are injected into a time-of-flight analyzer from a radio frequency (rf) trap, dispersed in time-of-flight according to their mass-to-charge ratios and then re-trapped dynamically in the same rf trap. This re-trapping technique is highly mass-selective and after sufficiently long flight times can provide even isobaric separation. A theoretical treatment of the method is presented and the conditions for optimum performance of the method are derived. The method has been implemented in a multiple-reflection time-of-flight mass spectrometer and mass separation powers (FWHM) in excess of 70,000, and re-trapping efficiencies of up to 35% have been obtained for the protonated molecular ion of caffeine. The isobars glutamine and lysine (relative mass difference of 1/4000) have been separated after a flight time of 0.2 ms only. Higher mass separation powers can be achieved using longer flight times. The method will have important applications, including isobar separation in nuclear physics and (ultra-)high-resolution precursor ion selection in multiple-stage tandem mass spectrometry. Graphical Abstract ᅟ

A liquid chromatography/time-of-flight mass spectrometry (LC-TOF-MS) method for targeted toxicological screening in human postmortem blood samples from forensic autopsy cases has been developed, validated and compared with a previously used method using gas chromatography with nitrogen–phosphorus detection (GC-NPD). Separation was achieved within 12 min by high-resolution gradient chromatography. Ions were generated in positive and negative electrospray ionization mode and were detected in 2-GHz single mass spectrometry mode, m / z range 50–1,000. Before injection, 0.25 g blood was prepared by protein precipitation with 500 μL of a mixture of acetonitrile and ethanol containing deuterated internal standards. An in-house database comprising 240 drugs and metabolites was built by analysing solutions from certified standards or other documented reference material available. Identification was based on scoring of retention time, accurate mass measurement and isotopic pattern. Validation was performed on spiked blood samples and authentic postmortem blood samples. The thresholds defined as minimum required performance levels were for most compounds in the range from 0.01 to 0.10 μg/g. Typically, a mass error of less than 2 ppm and a precision of area measurements of less than 5 % coefficient of variation were achieved. Positive identification was confirmed at concentrations up to 500 μg/g. Most compounds were determined in positive ionization mode, but for a limited number of compounds (fewer than 4 %) negative ionization was needed and a few early-eluted compounds could not be identified owing to substantial influence of interferences from the matrix and were thus not included in the screening. A robust and valid toxicological screening by LC-TOF-MS for postmortem blood samples, covering 50 % more compounds, and with higher precision and sensitivity than the previously used screening by GC-NPD was achieved.

Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (MS) and an alternative technology represented by direct analysis in real time coupled with quadrupole time-of-flight MS were investigated for metabolic fingerprinting of 343 red and white wine samples. Direct injection of pure wine and an extraction procedure optimized for isolation of polyphenols were used to compare different analytical and data handling strategies. After data processing and data pretreatment, principal component analysis was initially used to explore the data structure. Initially, the unsupervised models revealed a notable clustering according to the grape varieties, and therefore supervised orthogonal partial least squares discriminant analysis models were created and validated for separation of red and white wines according to the grape variety. The validated orthogonal partial least squares discriminant analysis models based on data (ions) recorded in positive ionization mode were able to classify correctly 95 % of samples. In parallel, authentication parameters, such as origin and vintage, were evaluated, and they are discussed. A tentative identification of markers was performed using accurate mass measurement of MS and MS/MS spectra, different software packages and different online libraries. In this way, different flavonol glucosides and polyphenols were identified as wine markers according to the grape varieties.

This paper presents a time-of-flight image sensor based on 8-Tap P-N junction demodulator (PND) pixels, which is designed for hybrid-type short-pulse (SP)-based ToF measurements under strong ambient light. The 8-tap demodulator implemented with multiple p-n junctions used for modulating the electric potential to transfer photoelectrons to eight charge-sensing nodes and charge drains has an advantage of high-speed demodulation in large photosensitive areas. The ToF image sensor implemented using 0.11 µm CIS technology, consisting of an 120 (H) × 60 (V) image array of the 8-tap PND pixels, successfully works with eight consecutive time-gating windows with the gating width of 10 ns and demonstrates for the first time that long-range (>10 m) ToF measurements under high ambient light are realized using single-frame signals only, which is essential for motion-artifact-free ToF measurements. This paper also presents an improved depth-adaptive time-gating-number assignment (DATA) technique for extending the depth range while having ambient-light canceling capability and a nonlinearity error correction technique. By applying these techniques to the implemented image sensor chip, hybrid-type single-frame ToF measurements with depth precision of maximally 16.4 cm (1.4% of the maximum range) and the maximum non-linearity error of 0.6% for the full-scale depth range of 1.0–11.5 m and operations under direct-sunlight-level ambient light (80 klux) have been realized. The depth linearity achieved in this work is 2.5 times better than that of the state-of-the-art 4-tap hybrid-type ToF image sensor.

The mechanisms responsible for macular edema with branch retinal vein occlusion (BRVO) remain to be elucidated. It is known that the expression profile of certain proteins in the aqueous humor (AH) changes in some diseases. Accordingly, determining the expression of these AH proteins may aid in the understanding of their potential role in this pathogenesis. The aim of this study was to identify the possible mechanisms involved in the development of BRVO-induced macular edema. A proteomic analysis of the AH composition in the eyes of patients with BRVO was performed and compared with that in the eyes of patients with cataract (non-BRVO; controls). AH from 6 patients with macular edema due to BRVO and 6 patients with cataract (non-BRVO) was collected. A proteomic approach which included 2-dimensional electrophoresis (2-DE) coupled with mass spectrometry (MS) and bioinformatics analysis were used to identify AH proteins with altered expression in patients with macular edema due to BRVO compared with the controls. An enzyme-linked immunosorbent assay was used to validate the proteomic results. The total protein concentration in the AH of patients with BRVO-induced macular edema was significantly greater than that of the controls. In the patients with BRVO, a total of 56 protein spots were significantly altered on the 2D gels. A total of 49 protein spots were identified by MS; many of these proteins have been implicated in angiogenesis, oxidative stress and collagen synthesis. In conclusion, the protein composition in AH differed significantly between the patients with BRVO and the controls. The identified proteins may be potential biomarkers for the development of macular edema due to BRVO and may play a role in the mechanisms responsible for it.

In this work, an ultrasound computed tomography (USCT) system was employed to investigate the fast-kinetic reactive crystallization process of calcium carbonate. USCT measurements and reconstruction provided key insights into the bulk particle distribution inside the stirred tank reactor and could be used to estimate the settling rate and settling time of the particles. To establish the utility of the USCT system for dynamical crystallization processes, first, the experimental imaging tasks were carried out with the stirred solid beads, as well as the feeding and stirring of the CaCO3 crystals. The feeding region, the mixing process, and the particles settling time could be detected from USCT data. Reactive crystallization experiments for CO2 capture were then conducted. Moreover, there was further potential for quantitative characterization of the suspension density in this process. USCT-based reconstructions were investigated for several experimental scenarios and operating conditions. This study demonstrates a real-time monitoring and fault detection application of USCT for reactive crystallization processes. As a robust noninvasive and nonintrusive tool, real-time signal analysis and reconstruction can be beneficial in the development of monitoring and control systems with real-world applications for crystallization processes. A diverse range of experimental studies shown here demonstrate the versatility of the USCT system in process application, hoping to unlock the commercial and industrial utility of the USCT devices.

We aim to synthesize brain time‐of‐flight (TOF) PET images/sinograms from their corresponding non‐TOF information in the image space (IS) and sinogram space (SS) to increase the signal‐to‐noise ratio (SNR) and contrast of abnormalities, and decrease the bias in tracer uptake quantification. One hundred forty clinical brain 18F‐FDG PET/CT scans were collected to generate TOF and non‐TOF sinograms. The TOF sinograms were split into seven time bins (0, ±1, ±2, ±3). The predicted TOF sinogram was reconstructed and the performance of both models (IS and SS) compared with reference TOF and non‐TOF. Wide‐ranging quantitative and statistical analysis metrics, including structural similarity index metric (SSIM), root mean square error (RMSE), as well as 28 radiomic features for 83 brain regions were extracted to evaluate the performance of the CycleGAN model. SSIM and RMSE of 0.99 ± 0.03, 0.98 ± 0.02 and 0.12 ± 0.09, 0.16 ± 0.04 were achieved for the generated TOF‐PET images in IS and SS, respectively. They were 0.97 ± 0.03 and 0.22 ± 0.12, respectively, for non‐TOF‐PET images. The Bland & Altman analysis revealed that the lowest tracer uptake value bias (−0.02%) and minimum variance (95% CI: −0.17%, +0.21%) were achieved for TOF‐PET images generated in IS. For malignant lesions, the contrast in the test dataset was enhanced from 3.22 ± 2.51 for non‐TOF to 3.34 ± 0.41 and 3.65 ± 3.10 for TOF PET in SS and IS, respectively. The implemented CycleGAN is capable of generating TOF from non‐TOF PET images to achieve better image quality. We aim to synthesize brain time‐of‐flight (TOF) PET images/sinograms from their corresponding non‐TOF information in the image space (IS) and sinogram space (SS) to increase the signal‐to‐noise ratio (SNR) and contrast of abnormalities, and decrease the bias in tracer uptake quantification. The implemented CycleGAN is capable of generating TOF from non‐TOF PET images to achieve better image quality.

Performance of systems for optical detection depends on the choice of the right detector for the right application. Designers of optical systems for ranging applications can choose from a variety of highly sensitive photodetectors, of which the two most prominent ones are linear mode avalanche photodiodes (LM-APDs or APDs) and Geiger-mode APDs or single-photon avalanche diodes (SPADs). Both achieve high responsivity and fast optical response, while maintaining low noise characteristics, which is crucial in low-light applications such as fluorescence lifetime measurements or high intensity measurements, for example, Light Detection and Ranging (LiDAR), in outdoor scenarios. The signal-to-noise ratio (SNR) of detectors is used as an analytical, scenario-dependent tool to simplify detector choice for optical system designers depending on technologically achievable photodiode parameters. In this article, analytical methods are used to obtain a universal SNR comparison of APDs and SPADs for the first time. Different signal and ambient light power levels are evaluated. The low noise characteristic of a typical SPAD leads to high SNR in scenarios with overall low signal power, but high background illumination can saturate the detector. LM-APDs achieve higher SNR in systems with higher signal and noise power but compromise signals with low power because of the noise characteristic of the diode and its readout electronics. Besides pure differentiation of signal levels without time information, ranging performance in LiDAR with time-dependent signals is discussed for a reference distance of 100 m. This evaluation should support LiDAR system designers in choosing a matching photodiode and allows for further discussion regarding future technological development and multi pixel detector designs in a common framework.