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 ¹¹ C 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.

In this paper, we report on SwissSPAD2, an image sensor with 512 × 512 photon-counting pixels, each comprising a single-photon avalanche diode (SPAD), a 1-b memory, and a gating mechanism capable of turning the SPAD on and off, with a skew of 250 and 344 ps, respectively, for a minimum duration of 5.75 ns. The sensor is designed to achieve a frame rate of up to 97 700 binary frames per second and sub-40 ps gate shifts. By synchronizing it with a pulsed laser and using multiple successive overlapping gates, one can reconstruct a molecule's fluorescent response with picosecond temporal resolution. Thanks to the sensor's number of pixels (the largest to date) and the fully integrated gated operation, SwissSPAD2 enables widefield fluorescence lifetime imaging microscopy with an all-solid-state solution and at relatively high frame rates. This was demonstrated with preliminary results on organic dyes and semiconductor quantum dots using both decay fitting and phasor analysis. Furthermore, pixels with an exceptionally low dark count rate and high photon detection probability enable uniform and high-quality imaging of biologically relevant fluorescent samples stained with multiple dyes. While future versions will feature the addition of microlenses and optimize firmware speed, our results open the way for low-cost alternatives to commercially available scientific time-resolved imagers.

Building a large-scale quantum computer requires the co-optimization of both the quantum bits (qubits) and their control electronics. By operating the CMOS control circuits at cryogenic temperatures (cryo-CMOS), and hence in close proximity to the cryogenic solid-state qubits, a compact quantum-computing system can be achieved, thus promising scalability to the large number of qubits required in a practical application. This work presents a cryo-CMOS microwave signal generator for frequency-multiplexed control of 4x 32 qubits (32 qubits per RF output). A digitally intensive architecture offering full programmability of phase, amplitude, and frequency of the output microwave pulses and a wideband RF front end operating from 2 to 20 GHz allow targeting both spin qubits and transmons. The controller comprises a qubit-phase-tracking direct digital synthesis (DDS) back end for coherent qubit control and a single-sideband (SSB) RF front end optimized for minimum leakage between the qubit channels. Fabricated in Intel 22-nm FinFET technology, it achieves a 48-dB SNR and 45-dB spurious-free dynamic range (SFDR) in a 1-GHz data bandwidth when operating at 3 K, thus enabling high-fidelity qubit control. By exploiting the on-chip 4096-instruction memory, the capability to translate quantum algorithms to microwave signals has been demonstrated by coherently controlling a spin qubit at both 14 and 18 GHz.