Towards a Multi-Pixel Photon-to-Digital Converter for Time-Bin Quantum Key Distribution.

We present an integrated single-photon detection device custom designed for quantum key distribution (QKD) with time-bin encoded single photons. We implemented and demonstrated a prototype photon-to-digital converter (PDC) that integrates an 8 × 8 single-photon avalanche diode (SPAD) array with on-chip digital signal processing built in TSMC 65 nm CMOS. The prototype SPADs are used to validate the QKD functionalities with an array of time-to-digital converters (TDCs) to timestamp and process the photon detection events. The PDC uses window gating to reject noise counts and on-chip processing to sort the photon detections into respective time-bins. The PDC prototype achieved a 22.7 ps RMS timing resolution and demonstrated operation in a time-bin setup with 158 ps time-bins at an optical wavelength of 410 nm. This PDC can therefore be an important building block for a QKD receiver and enables compact and robust time-bin QKD systems with imaging detectors.

3D Photon-to-Digital Converter for Radiation Instrumentation: Motivation and Future Works.

Analog and digital SiPMs have revolutionized the field of radiation instrumentation by replacing both avalanche photodiodes and photomultiplier tubes in many applications. However, multiple applications require greater performance than the current SiPMs are capable of, for example timing resolution for time-of-flight positron emission tomography and time-of-flight computed tomography, and mitigation of the large output capacitance of SiPM array for large-scale time projection chambers for liquid argon and liquid xenon experiments. In this contribution, the case will be made that 3D photon-to-digital converters, also known as 3D digital SiPMs, have a potentially superior performance over analog and 2D digital SiPMs. A review of 3D photon-to-digital converters is presented along with various applications where they can make a difference, such as time-of-flight medical imaging systems and low-background experiments in noble liquids. Finally, a review of the key design choices that must be made to obtain an optimized 3D photon-to-digital converter for radiation instrumentation, more specifically the single-photon avalanche diode array, the CMOS technology, the quenching circuit, the time-to-digital converter, the digital signal processing and the system level integration, are discussed in detail.

Simultaneous assessment of rodent behavior and neurochemistry using a miniature positron emission tomograph.

Positron emission tomography (PET) neuroimaging and behavioral assays in rodents are widely used in neuroscience. PET gives insights into the molecular processes of neuronal communication, and behavioral methods analyze the actions that are associated with such processes. These methods have not been directly integrated, because PET studies in animals have until now required general anesthesia to immobilize the subject, which precludes behavioral studies. We present a method for imaging awake, behaving rats with PET that allows the simultaneous study of behavior. Key components include the 'rat conscious animal PET' or RatCAP, a miniature portable PET scanner that is mounted on the rat's head, a mobility system that allows considerable freedom of movement, radiotracer administration techniques and methods for quantifying behavior and correlating the two data sets. The simultaneity of the PET and behavioral data provides a multidimensional tool for studying the functions of different brain regions and their molecular constituents.

Investigation of a Model-based Time-over-threshold Technique for Phoswich Crystal Discrimination.

The best crystal identification (CI) algorithms proposed so far for phoswich detectors are based on adaptive filtering and pulse shape discrimination (PSD). However, these techniques require free running analog to digital converters, which is no longer possible with the ever increasing pixelization of new detectors. We propose to explore the dual-threshold time-over-threshold (ToT) technique, used to measure events energy and time of occurence, as a more robust solution for crystal identification with broad energy windows in phoswich detectors. In this study, phoswich assemblies made of various combinations of LGSO and LYSO scintillators with decay times in the range 30 to 65 ns were investigated for the LabPET II detection front-end. The electronic readout is based on a 4 × 8 APD array where pixels are individually coupled to charge sensitive preamplifiers followed by first order CR-RC shapers with 75 ns peaking time. Crystal identification data were sorted out based on the measurements of likeliness between acquired signals and a time domain model of the analog front-end. Results demonstrate that crystal identification can be successfully performed using a dual-threshold ToT scheme with a discrimination accuracy of 99.1% for LGSO (30 ns)/LGSO (45 ns), 98.1% for LGSO (65 ns)/LYSO (40 ns) and 92.1% for LYSO (32 ns)/LYSO (47 ns), for an energy window of [350-650] keV. Moreover, the method shows a discrimination accuracy >97% for the two first pairs and ~90% for the last one when using a wide energy window of [250-650] keV.

PET Imaging of Leg Arteries for Determining the Input Function in PET/MRI Brain Studies Using a Compact, MRI-compatible PET System.

In this study, we used a compact, high-resolution, and MRI-compatible PET camera (VersaPET) to assess the feasibility of measuring the image-derived input function (IDIF) from arteries in the leg with the ultimate goal of enabling fully quantitative PET brain imaging without blood sampling. We used this approach in five 18F-FDG PET/MRI brain studies in which the input function was also acquired using the gold standard of serial arterial blood sampling. After accounting for partial volume, dispersion, and calibration effects, we compared the metabolic rates of glucose (MRglu) quantified from VersaPET IDIFs in 80 brain regions to those using the gold standard and achieved a bias and variability of <5% which is within the range of reported test-retest values for this type of study. We also achieved a strong linear relationship (R2 >0.97) against the gold standard across regions. The results of this preliminary study are promising and support further studies to optimize methods, validate in a larger cohort, and extend to the modeling of other radiotracers.

Roadmap toward the 10 ps time-of-flight PET challenge.

Since the seventies, positron emission tomography (PET) has become an invaluable medical molecular imaging modality with an unprecedented sensitivity at the picomolar level, especially for cancer diagnosis and the monitoring of its response to therapy. More recently, its combination with x-ray computed tomography (CT) or magnetic resonance (MR) has added high precision anatomic information in fused PET/CT and PET/MR images, thus compensating for the modest intrinsic spatial resolution of PET. Nevertheless, a number of medical challenges call for further improvements in PET sensitivity. These concern in particular new treatment opportunities in the context personalized (also called precision) medicine, such as the need to dynamically track a small number of cells in cancer immunotherapy or stem cells for tissue repair procedures. A better signal-to-noise ratio (SNR) in the image would allow detecting smaller size tumours together with a better staging of the patients, thus increasing the chances of putting cancer in complete remission. Moreover, there is an increasing demand for reducing the radioactive doses injected to the patients without impairing image quality. There are three ways to improve PET scanner sensitivity: improving detector efficiency, increasing geometrical acceptance of the imaging device and pushing the timing performance of the detectors. Currently, some pre-localization of the electron-positron annihilation along a line-of-response (LOR) given by the detection of a pair of annihilation photons is provided by the detection of the time difference between the two photons, also known as the time-of-flight (TOF) difference of the photons, whose accuracy is given by the coincidence time resolution (CTR). A CTR of about 10 picoseconds FWHM will ultimately allow to obtain a direct 3D volume representation of the activity distribution of a positron emitting radiopharmaceutical, at the millimetre level, thus introducing a quantum leap in PET imaging and quantification and fostering more frequent use of 11C radiopharmaceuticals. The present roadmap article toward the advent of 10 ps TOF-PET addresses the status and current/future challenges along the development of TOF-PET with the objective to reach this mythic 10 ps frontier that will open the door to real-time volume imaging virtually without tomographic inversion. The medical impact and prospects to achieve this technological revolution from the detection and image reconstruction point-of-views, together with a few perspectives beyond the TOF-PET application are discussed.

Real-Time Microfluidic Blood-Counting System for PET and SPECT Preclinical Pharmacokinetic Studies.

UNLABELLED: Small-animal nuclear imaging modalities have become essential tools in the development process of new drugs, diagnostic procedures, and therapies. Quantification of metabolic or physiologic parameters is based on pharmacokinetic modeling of radiotracer biodistribution, which requires the blood input function in addition to tissue images. Such measurements are challenging in small animals because of their small blood volume. In this work, we propose a microfluidic counting system to monitor rodent blood radioactivity in real time, with high efficiency and small detection volume (∼1 µL). METHODS: A microfluidic channel is built directly above unpackaged p-i-n photodiodes to detect ß-particles with maximum efficiency. The device is embedded in a compact system comprising dedicated electronics, shielding, and pumping unit controlled by custom firmware to enable measurements next to small-animal scanners. Data corrections required to use the input function in pharmacokinetic models were established using calibrated solutions of the most common PET and SPECT radiotracers. Sensitivity, dead time, propagation delay, dispersion, background sensitivity, and the effect of sample temperature were characterized. The system was tested for pharmacokinetic studies in mice by quantifying myocardial perfusion and oxygen consumption with (11)C-acetate (PET) and by measuring the arterial input function using (99m)TcO4 (-) (SPECT). RESULTS: Sensitivity for PET isotopes reached 20%-47%, a 2- to 10-fold improvement relative to conventional catheter-based geometries. Furthermore, the system detected (99m)Tc-based SPECT tracers with an efficiency of 4%, an outcome not possible through a catheter. Correction for dead time was found to be unnecessary for small-animal experiments, whereas propagation delay and dispersion within the microfluidic channel were accurately corrected. Background activity and sample temperature were shown to have no influence on measurements. Finally, the system was successfully used in animal studies. CONCLUSION: A fully operational microfluidic blood-counting system for preclinical pharmacokinetic studies was developed. Microfluidics enabled reliable and high-efficiency measurement of the blood concentration of most common PET and SPECT radiotracers with high temporal resolution in small blood volume.

Blood compatible microfluidic system for pharmacokinetic studies in small animals.

New radiotracer developments for nuclear medicine imaging require the analysis of blood as a function of time in small animal models. A microfluidic device was developed to monitor the radioactivity concentration in the blood of rats and mice in real time. The microfluidic technology enables a large capture solid angle and a reduction in the separation distance between the sample and detector, thus increasing the detection efficiency. This in turn allows a reduction of the required detection volume without compromising sensitivity, an important advantage with rodent models having a small total blood volume (a few ml). A robust fabrication process was developed to manufacture the microchannels on top of unpackaged p-i-n photodiodes without altering detector performance. The microchannels were fabricated with KMPR, an epoxy-based photoresist similar to SU-8 but with improved resistance to stress-induced fissuring. Surface passivation of the KMPR enables non-diluted whole blood to flow through the channel for up to 20 min at low speed without clotting. The microfluidic device was embedded in a portable blood counter with dedicated electronics, pumping unit and computer control software for utilisation next to a small animal nuclear imaging scanner. Experimental measurements confirmed model predictions and showed a 4- to 19-fold improvement in detection efficiency over existing catheter-based devices, enabling a commensurate reduction in sampled blood volume. A linear dose-response relationship was demonstrated for radioactivity concentrations typical of experiments with rodents. The system was successfully used to measure the blood input function of rats in real time after radiotracer injection.

Small animal simultaneous PET/MRI: initial experiences in a 9.4 T microMRI.

We developed a non-magnetic positron-emission tomography (PET) device based on the rat conscious animal PET that operates in a small-animal magnetic resonance imaging (MRI) scanner, thereby enabling us to carry out simultaneous PET/MRI studies. The PET detector comprises 12 detector blocks, each being a 4 × 8 array of lutetium oxyorthosilicate crystals (2.22 × 2.22 × 5 mm(3)) coupled to a matching non-magnetic avalanche photodiode array. The detector blocks, housed in a plastic case, form a 38 mm inner diameter ring with an 18 mm axial extent. Custom-built MRI coils fit inside the positron-emission tomography (PET) device, operating in transceiver mode. The PET insert is integrated with a Bruker 9.4 T 210 mm clear-bore diameter MRI scanner. We acquired simultaneous PET/MR images of phantoms, of in vivo rat brain, and of cardiac-gated mouse heart using [(11)C]raclopride and 2-deoxy-2-[(18)F]fluoro-D-glucose PET radiotracers. There was minor interference between the PET electronics and the MRI during simultaneous operation, and small effects on the signal-to-noise ratio in the MR images in the presence of the PET, but no noticeable visual artifacts. Gradient echo and high-duty-cycle spin echo radio frequency (RF) pulses resulted in a 7% and a 28% loss in PET counts, respectively, due to high PET counts during the RF pulses that had to be gated out. The calibration of the activity concentration of PET data during MR pulsing is reproducible within less than 6%. Our initial results demonstrate the feasibility of performing simultaneous PET and MRI studies in adult rats and mice using the same PET insert in a small-bore 9.4 T MRI.