Abstract
SIGNIFICANCE: Single-photon-level imaging has been utilized for decades in closed dark environments; however, the utility for macroscopic imaging is more limited because it involves time-gating, filtering, and processing to view signals of interest. In radiation therapy delivery, a low-level signal called Cherenkov emission occurs from patients' bodies, which is imaged with single-photon level sensitivity, mapping radiation dose deposition in tissue. Several key technological advances have been leveraged to make this extremely low-light signal overcome high background and noise in clinical settings. AIM: Our review summarizes specific technological advances that have led to a single-photon imaging in high radiation noise and high optical background environments possible. Our work discusses applications and future opportunities. APPROACH: Physical fundamentals of Cherenkov light, ambient room light, optical filtering, time-gating, and image processing are reviewed with key technological camera choices. This is followed by discussion of image quality, noise, and postprocessing, with current and future applications. RESULTS: Invention and optimization of time-gating techniques and cameras with a single-photon capability were required to achieve real-time Cherenkov imaging. Requirements of video frame rate ( ≈ 10 to 30 fps), fast triggering ( ≈ μs ), clinically relevant spatial resolution ( ≈ mm ), single-photon/pixel sensitivity, and large field of view all led to intensified complementary metal-oxide-semiconductor cameras. Additional innovations in wavelength filtering, lens choices, and spatial and temporal postprocessing have allowed imaging that is not overwhelmed by ambient radiation noise or room lights. The current use provides real-time visualization of external beam radiotherapy on patient's skin. Several emerging research areas may improve image quality and provide additional capabilities in biochemical sensing and quantification of delivery. CONCLUSION: The technical inventions and discoveries on how this light signal is sampled have led to real-time beam observation for dose delivery verification in settings where single-photon sensitive imaging is seemingly implausible while also opening the door to additional research applications.