UTOFPET is a European H2020 research project within the PHOTONIC SENSING call. The international consortium is lead by the University of Pisa (Italy) and consists further of Ghent University (Belgium), AGE Scientific s.r.l (Italy), Ecole polytechnique federal de Lausanne (Suisse) and MOLECUBES NV (Belgium).
Multi-parametric molecular imaging (MMI) is an imaging modality largely based on clinical PET that allowed many of the recent discoveries on new molecular probes and the associated models. MMI is a fundamental pillar of the so-called personalised medicine that is expected to allow the delivery of “the right treatment to the right patient at the right time”. There is a general consensus on the necessity of increasing MMI sensitivity by at least a factor of ten in order to exploit its full potential. This project aims at providing a new type of time-of-flight (TOF) PET demonstrator that is expected to drive such a big leap in sensitivity. In TOF-PET, the timing information of each annihilation photon coming from the source under examination is used to improve the statistical information regarding the position of the source itself. It can be demonstrated that TOF can introduce a gain in the PET sensitivity that is approximately proportional to the inverse of the resolving time of its photon detectors. Therefore, one way to increase sensitivity is by improving the TOF resolution.
This project includes developments on both TOF-PET hardware and software aimed at improving the TOF resolution beyond the level achievable today with analogue SiPMs. A PET prototype will be constructed based on the emerging type of photosensor devices known as multichannel digital SiPM and the latest scintillating materials and photonic crystals technologies. A scalable acquisition system will be developed to handle the high data rate produced by each detector.
The system will provide timing performances beyond the state of the art, well below 300-400 ps, which will translate into higher imaging sensitivity, higher contrast, lower noise, faster convergence and improved robustness with respect to state of the art PET and TOF-PET alternatives.
Background and vision
Integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) represent the state of the art in multi-parametric in-vivo molecular imaging (MMI), i.e., one of the emerging technologies in medical applications and “personalised medicine”. New PET molecular probes and associated small animal imaging models are under development to find and quantify subtle molecular and cellular processes such as protein interactions, cancer cell interactions with the immune system, therapeutic stem cells proliferation, gene delivery and expression in living subjects .
PET provides unparalleled sensitivity, especially when capable of measuring the difference in time of flight (TOF) of the two positron-electron annihilation photons. MRI provides morphological images with high resolution and exceptionally high soft-tissue contrast. When fully integrated, TOF-PET/MRI gives the most valuable molecular information available today on a living subject. By providing the physiological characteristics and biological behaviour of the diseased lesion, in addition to its location and extent, it is believed that MMI is close to taking diagnostics beyond the early detection of diseases. It is also expected that MMI will allow treating the disease not only on the basis of the symptoms but also of the biochemical profile of an individual’s disease state . To achieve these goals, the sensitivity offered by current TOF-PET/MRI needs a leap ahead of one order of magnitude . PET sensitivity depends on the detectors geometry: it increases with the detectors size and with their proximity to the subject. In the U.S., the NIH-funded project Explorer is bringing this aspect to its limits with a detector that is 2 meters long, 80 cm inner diameter, and whose expected sensitivity is 43 kcps/MBq – roughly 2 to 7 times higher than state of the art whole-body TOF-PET scanners [4,5]. Such a system is said to be “totalbody”, to hint at the fact that the axial extent of the scanner is much longer than usual, as opposed to the more conventional “whole-body” designation. The retained system concept is effective but intrinsically expensive, as it is primarily based on a multiplication of conventional block detectors.
A European research approach to the same problem follows the alternative direction of improving the TOF technology by bringing its coincidence time resolution (CTR) to the 10 ps limit . The principle is that the signal-to-noise ratio gain in a TOF-PET system is inversely proportional to the square root of the CTR .
This signal-to-noise gain translates to a gain in sensitivity. A CTR of 10 ps would be roughly 30 times better than any commercial system available today , and 50 times better than the Explorer PET CTR up to specs (530 ps simulated ). Therefore, a 10 ps TOF-PET system could have virtually the same sensitivity as the Explorer, with 7 times fewer detectors, while still keeping the MR-compatibility. The feasibility of sub-100 ps CTR has been already demonstrated with small scintillating calcium/cerium codoped L(Y)SO:Ca,Ce scintillating crystals . Modern Silicon photomultipliers (SiPM) proved in laboratory that timing resolutions below 100 ps can be achieved in PET. Digital SiPMs (dSiPMs) brought to laboratory practice the estimation of 511 keV photons arrival time from the triggering time of the first few scintillation photons . This practice led to the proposal of building networks of single photon avalanche diodes (SPAD-Nets) to acquire every single scintillation photon independently and thus pulling the timing resolution down to the fundamental physical limit of the scintillator [11,12]. This project intends to leverage this latest type of photodetectors to push the state of the art of PET technology towards the 10 ps limit. In order to do so, we intend to develop and validate in laboratory a novel concept photodetector design based on single photon sensing technologies, distributed on-chip real-time photon processing and advanced TOF-grade reconstruction techniques. This development effort is planned for a time frame of three years.
 Gu E. et al., Theranostics. 2012;2:335–345.
 White paper, ESR, Insights Imaging. 2015;6:141–155.
 Levin C.S., Proc. IEEE. 2008;96:439–467.
 Cherry S.R. et al., http://dx.doi.org/10.1117/12.2227151.
 Vandenberghe S. et al., EJNMMI Phys. 2016;3:3.
 Gundacker S. et al., PMB 2016;61:2802.
 Conti M., EJNMMI. 2011;38:1147–1157.
 Zhang X. et al., J. Nucl. Med. 2014;55:269–269.
 Nemallapudi M.V. et al., PMB 2015;60:4635.
 Seifert S. et al., PMB 2012;57:1797.
 Fishburn M.W. et al.,IEEE TNS 2010;57:2549–2557.
 Venialgo E. et al., PMB 2015;60:2435.