Machine learning has found unique applications in nuclear medicine from photon detection to quantitative image reconstruction. While there have been impressive strides in detector development for time-of-flight positron emission tomography, most detectors still make use of simple signal processing methods to extract the time and position information from the detector signals. Now with the availability of fast waveform digitizers, machine learning techniques have been applied to estimate the position and arrival time of high-energy photons. In quantitative image reconstruction, machine learning has been used to estimate various corrections factors, including scattered events and attenuation images, as well as to reduce statistical noise in reconstructed images. Here machine learning either provides a faster alternative to an existing time-consuming computation, such as in the case of scatter estimation, or creates a data-driven approach to map an implicitly defined function, such as in the case of estimating the attenuation map for PET/MR scans. In this article, we will review the abovementioned applications of machine learning in nuclear medicine.

In a scintillation detector, the light generated in the scintillator by a gamma interaction is converted to photoelectrons by a photodetector and produces a time-dependent waveform, the shape of which depends on the scintillator properties and the photodetector response. Several depth-of-interaction (DOI) encoding strategies have been developed that manipulate the scintillator's temporal response along the crystal length and therefore require pulse shape discrimination techniques to differentiate waveform shapes. In this work, we demonstrate how maximum likelihood (ML) estimation methods can be applied to pulse shape discrimination to better estimate deposited energy, DOI and interaction time (for time-of-flight (TOF) PET) of a gamma ray in a scintillation detector. We developed likelihood models based on either the estimated detection times of individual photoelectrons or the number of photoelectrons in discrete time bins, and applied to two phosphor-coated crystals (LFS and LYSO) used in a previously developed TOF-DOI detector concept. Compared with conventional analytical methods, ML pulse shape discrimination improved DOI encoding by 27% for both crystals. Using the ML DOI estimate, we were able to counter depth-dependent changes in light collection inherent to long scintillator crystals and recover the energy resolution measured with fixed depth irradiation (~11.5% for both crystals). Lastly, we demonstrated how the Richardson-Lucy algorithm, an iterative, ML-based deconvolution technique, can be applied to the digitized waveforms to deconvolve the photodetector's single photoelectron response and produce waveforms with a faster rising edge. After deconvolution and applying DOI and time-walk corrections, we demonstrated a 13% improvement in coincidence timing resolution (from 290 to 254 ps) with the LFS crystal and an 8% improvement (323 to 297 ps) with the LYSO crystal.