For a long time the discovery of new scintillators has been more serendipitous than driven by a deep understanding of the mechanisms at the origin of the scintillation process This situation has dramatically changed since the 1990's with an increased demand for scintillators of better performance for large particle physics experiments as well as for medical imaging It is now possible to design a scintillator for a specific purpose The bandgap can be adjusted, the traps energy levels and their concentration can be finely tuned and their influence can be damped or on the contrary enhanced by specific doping for an optimization of the performance of the scintillator Several examples are given in this paper of such crystal engineering attempts to improve the performance of crystal scintillators used in medical imaging devices An attention is also given to spectacular progress in crystal production technologies, which open new perspectives for large scale and cost effective crystal production with consistent quality

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Development of new scintillators for medical applications

Single-photon avalanche diode (SPAD) arrays are solid-state detectors that offer imaging capabilities at the level of individual photons, with unparalleled photon counting and time-resolved performance. This fascinating technology has progressed at a very fast pace in the past 15 years, since its inception in standard CMOS technology in 2003. A host of architectures have been investigated, ranging from simpler implementations, based solely on off-chip data processing, to progressively "smarter" sensors including on-chip, or even pixel level, time-stamping and processing capabilities. As the technology has matured, a range of biophotonics applications have been explored, including (endoscopic) FLIM, (multibeam multiphoton) FLIM-FRET, SPIM-FCS, super-resolution microscopy, time-resolved Raman spectroscopy, NIROT and PET. We will review some representative sensors and their corresponding applications, including the most relevant challenges faced by chip designers and end-users. Finally, we will provide an outlook on the future of this fascinating technology.

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Single-photon avalanche diode imagers in biophotonics: review and outlook

There is an increasing demand for high sensitivity multiparametric medical imaging approaches. High precision time-of-flight positron emission tomography (TOFPET) scanners have a very high potential in this context, providing an improvement in the signal-to-noise ratio of the reconstructed image and the possibility to further increase the already very high sensitivity (at the pico-molar level) of PET scanners. If the present state-of-the art coincidence time resolution of about 500 ps can be improved, it will open the way in particular to a significant reduction of the dose injected to the patient, and consequently, to the possibility to extend the use of PET scans to new categories of patients. This paper will describe the systematic approach followed by a number of researchers worldwide to push the limits of TOFPET imaging to the sub-100 ps level. It will be shown that the possibility to reach 10 ps, although extremely challenging, is not limited by physical barriers and that a number of disruptive technologies are presently being investigated at the level of all the components of the detection chain to gain at least a factor of 10 as compared to the present state-of-the-art.

Pushing the Limits in Time-of-Flight PET Imaging

An 8 × 16 pixel array based on CMOS small-area silicon photomultipliers (mini-SiPMs) detectors for PET applications is reported. Each pixel is 570 × 610 μm2 in size and contains four digital mini-SiPMs, for a total of 720 SPADs, resulting in a full chip fill-factor of 35.7%. For each gamma detection, the pixel provides the total detected energy and a timestamp, obtained through two 7-b counters and two 12-b 64-ps TDCs. An adder tree overlaid on top of the pixel array sums the sensor total counts at up to 100 Msamples/s, which are then used for detecting the asynchronous gamma events on-chip, while also being output in real-time. Characterization of gamma detection performance with an 3 × 3 × 5 mm3 LYSO scintillator at 20°C is reported, showing a 511-keV gamma energy resolution of 10.9% and a coincidence timing resolution of 399 ps.

A Fully Digital 8 $\,\times\,$ 16 SiPM Array for PET Applications With Per-Pixel TDCs and Real-Time Energy Output

The recent developments in time-domain diffuse optics that rely on physical concepts (e.g., time-gating and null distance) and advanced photonic components (e.g., vertical cavity source-emitting laser as light sources, single photon avalanche diode, and silicon photomultipliers as detectors, fast-gating circuits, and time-to-digital converters for acquisition) are focused. This study shows how these tools could lead on one hand to compact and wearable time-domain devices for point-of-care diagnostics down to the consumer level and on the other hand to powerful systems with exceptional depth penetration and sensitivity.

https://www.spiedigitallibrary.org/journals/Journal-of-Biomedical-Optics/volume-21/issue-9/091310/New-frontiers-in-time-domain-diffuse-optics-a-review/10.1117/1.JBO.21.9.091310.pdf

New frontiers in time-domain diffuse optics, a review

We present a single-photon avalanche diode (SPAD) with a wide spectral range fabricated in an advanced 180 nm CMOS process. The realized SPAD achieves 20 % photon detection probability (PDP) for wavelengths ranging from 440 nm to 820 nm at an excess bias of 4 V, with 30 % PDP at wavelengths from 520 nm to 720 nm. Dark count rates (DCR) are at most 5 kHz, which is 30 Hz/μm2, at an excess bias of 4V when we measure 10 μm diameter active area structure. Afterpulsing probability, timing jitter, and temperature effects on DCR are also presented.

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A wide spectral range single-photon avalanche diode fabricated in an advanced 180 nm CMOS technology.

This paper presents a comprehensive statistical analysis of timing resolution in a digital silicon photomultiplier (DSiPM) when multi timestamp is available. We look at the effect of dart count rate (DCR) on timing resolution in these devices as compared to analog silicon photomultipliers (A-SiPMs). The analysis includes photon detection efficiency (PDE), DCR, electrical jitter of the detector with a LYSO crystal. Timing resolution is analyzed utilizing a single timestamp or multiple timestamps. Simulation results show that D-SiPMs utilizing multiple timestamps (Multi-channel D-SiPM) can be more tolerant to DCR than those utilizing a single timestamp. The timing resolution is 13%, 20% and 40% better at 1000 detected photons, 200 ps rise time and 40 ns decay time of a LYSO scintillator, without DCR, with 1 MHz DCR and with 10 MHz DCR, respectively. Based on these findings, we propose new architectures to acquire multiple timestamps without sacrificing fill-factor. This paper also includes the implementation and characterization of 4 × 4 Multichannel D-SiPMs coupled with an array of 44ps LSB TDCs for coincidence detection of gamma rays. The pitch of the SiPMs is 800 μm and the number of pixels in one SiPM is 416. The pixel has a 57% fill factor with 121 ps timing resolution for a single photon. The SiPM timing resolution for single photon detection is 179 ps FWHM.

Multi-channel digital SiPMs: Concept, analysis and implementation

A sensing device includes a first array of sensing elements, which output a signal indicative of a time of incidence of a single photon on the sensing element. A second array of processing circuits are coupled respectively to the sensing elements and comprise a gating generator, which variably sets a start time of the gating interval for each sensing element within each acquisition period, and a memory, which records the time of incidence of the single photon on each sensing element in each acquisition period. A controller controls the gating generator during a first sequence of the acquisition periods so as to sweep the gating interval over the acquisition periods and to identify a respective detection window for the sensing element, and during a second sequence of the acquisition periods, to fix the gating interval for each sensing element to coincide with the respective detection window.

SPAD array with gated histogram construction

This paper demonstrates a TDA, whose input time difference is amplified into the output time difference. Cross coupled chains of variable delay cells with the same number of stages are applicable for TDA, and the gain is adjusted via DLL-like closed-loop control. The TDA was fabricated using 65nm CMOS and the measurement results shows that the time difference gain is 4.78 at a nominal power supply while the designed gain is 4.0. The gain is stable enough to be less than 1.4% gain shift under ± 10% power supply voltage fluctuation.

Time difference amplifier using closed-loop gain control

We present a 4 X 4 array of digital silicon photomultipliers (D-SiPMs) capable of timestamping up to 48 photons per D-SiPM and we show the advantage of generating multiple timestamps in the context of positron emission tomography (PET). The D-SiPMs have a pitch of 800 ?m and comprise 416 pixels each; the timing resolution achieved by the SiPMs is 179 ps FWHM, while each pixel has a fill factor of up to 57% and a single-photon timing resolution of 114 ps.

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Shingo Mandai

Papers

A wide spectral range single-photon avalanche diode fabricated in an advanced 180 nm CMOS technology.

Multi-channel digital SiPMs: Concept, analysis and implementation

SPAD array with gated histogram construction

Time difference amplifier using closed-loop gain control

A 4 X 4 X 416 digital SiPM array with 192 TDCs for multiple high-resolution timestamp acquisition