Imaging issues specific to hadrontherapy (proton, carbon, helium therapy and other charged particles) for radiotherapy planning, setup, dose monitoring and tissue response assessment

Imaging is critical to each step of precision radiation therapy, i.e. planning, setup, delivery and assessment of response. Hadrontherapy can be considered to deliver more precise dose distribution that may better spare normal tissues from intermediate low doses of radiation. In addition, hadrontherapy using high linear energy transfer ions may also be used for dose escalation on biological target volumes defined by functional imaging. However, the physical characteristics of hadrontherapy also make it more demanding in terms of imaging accuracy and image-based dose calculation. Some of the developments needed in imaging are specific to hadrontherapy. The current review addresses current status of imaging in proton therapy and the drawbacks of photon-based imaging for hadrons. It also addresses requirements in hadrontherapy planning with respect to multimodal imaging for proper target and organ at risk definition as well as to target putative radioresistant areas such as hypoxic ones, and with respect to dose calculation using dual energy CT, MR-proton therapy, proton radiography. Imaging modalities, such as those used in photon-based radiotherapy (intensity modulated and stereotactic radiotherapy), are somewhat already implemented or should be reaching "routine" hadrontherapy (at least proton therapy) practice in planning, repositioning and response evaluation optimizable within the next five years. Online monitoring imaging by PET, as currently developed for hadrontherapy, is already available. Its spatiotemporal limits restrict its use but similar to prompt gamma detection, represents an area of active research for the next 5 to 10 years. Because of the more demanding and specific dose deposit characteristics, developments image-guided hadrontherapy, such as specific proton imaging using tomography or ionoacoustics, as well as delivery with MR-proton therapy, may take another 10 years to reach the clinics in specific applications. Other aspects are briefly described such as range monitoring. Finally, the potential of imaging normal tissue changes and challenges to assess tumour response are discussed.