Ultra-fast imaging for the safe delivery of electron FLASH radiation therapy

Abstract Radiation therapy is a supplementary curative treatment used adjuvant with most surgery and chemotherapy, being delivered to nearly 1 out of every 4 people in their lifetime. While image guidance and conformal planning reduced the dose to healthy tissue, there is still a substantial risk of tissue damage that sets the upper limit of dose deposited to the tumor. A recent radical approach to minimize healthy tissue damage was demonstrated with ultra-high dose rate irradiation, and is known as the FLASH effect. This treatment operates at dose rates 1000x higher than in conventional mode, and by delivering an entire treatment course in 100 millisecond, it promises a reduction of radiation-induced toxicities by 10-50%. Several clinical centers, including Dartmouth Hitchcock Clinic, demonstrated that an existing clinical linac can be reversibly converted into an ultra-high dose rate electron source. This modification shows enormous translational potential to deliver electron FLASH (eFLASH) in any radiotherapy center using existing systems. However, while most research in the field is focused on elucidating the radiobiological mechanisms of FLASH, work towards mitigating the risks of FLASH is largely untouched, yet will be pivotal for wide clinical implementation. New techniques for detection monitoring radiation need to be developed due to the millisecond timescales at which FLASH operates which make traditional methods unsuitable. In this project, we exploit the uniqueness of DoseOptics BeamSiteTM system, a recently 510(k) cleared single photon capable camera designed to monitor conventional radiotherapy providing the first direct videos of the radiation dose delivery. BeamSite images are used by radiation therapists to monitor radiation delivery real-time. Clinical use has shown that routine monitoring of radiotherapy can reveal sub-optimal delivery which can be addressed by the therapists as needed. More importantly, it offers an automatic detection of beam and patient misalignments and delivery errors, and therefore it is very scalable even to the ultra-fast FLASH application. In this Phase I project we propose to develop an ultra-fast version of the BeamSite camera capable of tracking the beam on patients at kiloframe/s frame rate, which is required to keep up with the standard 360 Hz beam pulse rate in order to provide critically needed beam location and a linear and scalable dosimetry at these ultra-high dose rates. Once the camera is developed, these methods will be studied on DHMC’s existing clinical dual-purpose FLASH linac. The current proposal provides resources for the goals of: (i) developing a hardware prototype of an ultra-fast Cherenkov camera equipped with optimized, firmware-based algorithms, and (ii) demonstrating its capabilities for detecting beam deviations and dose on an existing eFLASH linac. The work includes hardware and software support and development, and eFLASH resources at Dartmouth Hitchcock to be leveraged towards these goals.Narrative Cherenkov imaging by BeamSite™ offers a fundamentally new paradigm in radiotherapy, whereby the therapy team can actually see what they are doing for the first time in the history of radiation treatment. Close monitoring of the treatment sites will become even more important with the emergence of FLASH radiotherapy, which introduces additional risks but offers the prospect of improved tissue sparing while maintaining the tumor killing response. With the assistance of this proposed Phase I project we will develop a unique high speed imaging system to safely deliver precise ultra-high dose rate electron therapy.