State of the art and challenges of time-of-flight PET.

After a brief review of the history of time-of-flight (TOF) positron emission tomography (PET) instrumentation from the 1980s to present, the principles of TOF PET are introduced, the concept of time resolution and its effect on TOF gain in signal-to-noise ratio (SNR) are discussed. The factors influencing the time resolution of a TOF PET scanner are presented, with focus on the intrinsic properties of scintillators of particular interest for TOF PET. Finally, some open issues, challenges and achievements of today's TOF PET reconstruction are reviewed: the structure of the data organization, the choice of analytical or iterative method, the recent experimental assessment of TOF image quality, and the most promising applications of TOF PET.