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 C-11 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.

SPADnet: a fully digital, scalable and networked photonic component for time-of-flight PET applications

Claudio Bruschini, Edoardo Charbon, Gabor Nemeth, John Richard Walker

The SPADnet FP7 European project is aimed at a new generation of fully digital, scalable and networked photonic components to enable large area image sensors, with primary target gamma-ray and coincidence detection in (Time-of-Flight) Positron Emission Tomography (PET). SPADnet relies on standard CMOS technology, therefore allowing for MRI compatibility. SPADnet innovates in several areas of PET systems, from optical coupling to single-photon sensor architectures, from intelligent ring networks to reconstruction algorithms. It is built around a natively digital, intelligent SPAD (Single-Photon Avalanche Diode)-based sensor device which comprises an array of 8x16 pixels, each composed of 4 mini-SiPMs with in situ time-to-digital conversion, a multi-ring network to filter, carry, and process data produced by the sensors at 2Gbps, and a 130nm CMOS process enabling mass-production of photonic modules that are optically interfaced to scintillator crystals. A few tens of sensor devices are tightly abutted on a single PCB to form a so-called sensor tile, thanks to TSV (Through Silicon Via) connections to their backside (replacing conventional wire bonding). The sensor tile is in turn interfaced to an FPGA-based PCB on its back. The resulting photonic module acts as an autonomous sensing and computing unit, individually detecting gamma photons as well as thermal and Compton events. It determines in real time basic information for each scintillation event, such as exact time of arrival, position and energy, and communicates it to its peers in the field of view. Coincidence detection does therefore occur directly in the ring itself, in a differed and distributed manner to ensure scalability. The selected true coincidence events are then collected by a snooper module, from which they are transferred to an external reconstruction computer using Gigabit Ethernet. We will detail the SPADnet core technologies as well as the latest project achievements in all project areas.

Spie-Int Soc Optical Engineering2014

SPADnet: Embedded coincidence in a smart sensor network for PET applications

Claudio Bruschini, Edoardo Charbon, Gabor Nemeth

n this paper we illustrate the core technologies at the basis of the European SPADnet project (www.spadnet.eu), and present the corresponding first results. SPADnet is aimed at a new generation of MRI-compatible, scalable large area image sensors, based on CMOS technology, that are networked to perform gamma-ray detection and coincidence to be used primarily in (Time-of-Flight) Positron Emission Tomography (PET). The project innovates in several areas of PET systems, from optical coupling to single-photon sensor architectures, from intelligent ring networks to reconstruction algorithms. In addition, SPADnet introduced the first computational model enabling study of the full chain from gamma photons to network coincidence detection through scintillation events, optical coupling, etc.

Elsevier2014

Near-Infrared Optical Tomography with Single-Photon Avalanche Diode Image Sensors

Juan Mata Pavia

In the past decades different methods based on magnetic resonance imaging (MRI) and positron emission tomography (PET) have been developed to image a variety of hemodynamic parameters in tissue. However, simultaneous high resolution imaging of oxy- and deoxyhemoglobin is not yet possible in clinical practices with millimeter accuracy. Near-infrared Spectroscopy (NIRS) is a well established technique that has been widely utilized in research and clinical practice to monitor the concentration of different chromophores in blood. It is capable of measuring a variety of parameters such as oxygenation levels in tissue, hematocrit, and cytochrome c oxidase levels among others. By increasing the amount and complexity of the light sources and detectors integrated in NIRS systems, in the last years researchers have been able to acquire tomographic images of such chromophores. This new imaging modality is known by different names: near-infrared optical tomography (NIROT), optical tomography (OT), diffuse optical tomography (DOT), or diffuse optical imaging (DOI). One of the main factors that limited the quality of the tomographic images obtained with NIROT has been the low number of sources and detectors employed in NIROT systems. The integration of the first single-photon avalanche diode (SPAD) together with time-to-digital converters (TDCs) in CMOS enabled a whole new range of possibilities in the field of single-photon detection. In this thesis the application of a SPAD-TDC image sensor in NIROT is presented for the first time. The main objective was to develop a new system that could perform acquisitions nearly in real time and that was capable of delivering tomographic images in a short period of time for medical evaluation. A new optical setup was conceived based on this detector to take advantage of the large amount of information delivered by the SPADs. By employing line-shaped illumination sources instead of point like sources, the target is more homogeneously illuminated and consequently a reduced number of sources is necessary. It was experimentally demonstrated that a resolution of 5 mm is possible with this new NIROT system. New algorithms that reduced the ill-posed nature of the image reconstruction problem were developed thanks to the wide-field time-resolved measurements delivered by the SPAD image sensors. The large datasets obtained with our NIROT system and its time-resolved capabilities enabled the development of fast methods capable of reconstructing an image with millimeter resolution in a few seconds with a laptop computer. We also analyze the effect of microlenses on the light sensitivity of the image sensor, showing that it is possible to increase it by a factor of 10 under certain conditions. A new image sensor with 4x400 pixels implemented in a 3D CMOS technology for NIROT applications is also presented. To our knowledge, this is the first backside illuminated SPAD array that incorporates in-pixel TDCs. A novel TDC architecture was introduced that reduces the energy consumed per conversion, consequently allowing a high number of TDCs working in parallel. The study of how NIROT can benefit from SPAD image sensors is presented in this thesis. Despite their current limitations, they enable the implementation of systems with thousands of detectors capable of millimeter resolution. Further developments in SPAD array architectures and TDCs will continue improving the performance of time-resolved NIROT systems.