Image guidance for FLASH radiotherapy.

FLASH radiotherapy (FLASH-RT) is an emerging ultra-high dose (>40 Gy/s) delivery that promises to improve the therapeutic potential by limiting toxicities compared to conventional RT while maintaining similar tumor eradication efficacy. Image guidance is an essential component of modern RT that should be harnessed to meet the special emerging needs of FLASH-RT and its associated high risks in planning and delivering of such ultra-high doses in short period of times. Hence, this contribution will elaborate on the imaging requirements and possible solutions in the entire chain of FLASH-RT treatment, from the planning, through the setup and delivery with online in vivo imaging and dosimetry, up to the assessment of biological mechanisms and treatment response. In patient setup and delivery, higher temporal sampling than in conventional RT should ensure that the short treatment is delivered precisely to the targeted region. Additionally, conventional imaging tools such as cone-beam computed tomography will continue to play an important role in improving patient setup prior to delivery, while techniques based on magnetic resonance imaging or positron emission tomography may be extremely valuable for either linear accelerator (Linac) or particle FLASH therapy, to monitor and track anatomical changes during delivery. In either planning or assessing outcomes, quantitative functional imaging could supplement conventional imaging for more accurate utilization of the biological window of the FLASH effect, selecting for or verifying things such as tissue oxygen and existing or transient hypoxia on the relevant timescales of FLASH-RT delivery. Perhaps most importantly at this time, these tools might help improve the understanding of the biological mechanisms of FLASH-RT response in tumor and normal tissues. The high dose deposition of FLASH provides an opportunity to utilize pulse-to-pulse imaging tools such as Cherenkov or radiation acoustic emission imaging. These could provide individual pulse mapping or assessing the 3D dose delivery superficially or at tissue depth, respectively. In summary, the most promising components of modern RT should be used for safer application of FLASH-RT, and new promising developments could be advanced to cope with its novel demands but also exploit new opportunities in connection with the unique nature of pulsed delivery at unprecedented dose rates, opening a new era of biological image guidance and ultrafast, pulse-based in vivo dosimetry.