# Transformative Technology for FLASH Radiation Therapy
## FLASH Studies with Laser-Driven Particle Sources Developed at Lawrence Berkeley National Laboratory
### Outlook for Laser-Driven FLASH  
To summarize, current LD particle-source parameters are well below the requirements for their use as an alternative medical FLASH radiotherapy modality. However, their comparatively low cost and compact nature has earned LD particle sources increasing attention and the differential normal vs. tumor cell sparing in vitro under LD proton irradiation was recently demonstrated [88]. Therefore, LD particle sources could soon complement conventional accelerators to increase and democratize access to particle sources for preclinical radiobiological research. This real-world application can serve as a stepping stone to further advance LD particle sources to the necessary capabilities to provide particle beams for FLASH radiotherapy.  
High-Peak-Current Linear Induction Accelerator (LIA) for FLASH-RT Developed at Lawrence Livermore National Laboratory  
Meeting the requirements for reproducible FLASH effects of \(>\)1.8 \(\times\) 10\({}^{5}\) Gy/s IDR with an overall irradiation time \(<\)200 ms (\(>\)40 Gy/s average dose rate for healthy tissue sparing) using deep-penetrating MV bremsstrahlung requires tens of amperes of pulsed electron beams at a high pulse-repetition frequency (PRF) [2,116]. These dose rate criteria must not only be met in the core of the irradiated volume but in the whole of the volume as well (i.e., beam penumbra and exit edge) [21].  
The pulsed-power-based linear induction accelerator (LIA) using a multilayered bremsstrahlung conversion target meets these demanding requirements. Complementary irradiation sources from the same accelerator structure ensure that the whole of the irradiated volume is above the FLASH threshold. The LIA acceleration technique stores energy during the interpulse time and then discharges it in a short, 10s-of-nanoseconds pulse to achieve extremely high IDR. This method is a direct acceleration technique using _induction_ and does not require RF or microwave generation as an intermediate step. When operated at a clinician-specified kilohertz PRF, equivalent dose rates exceeding the healthy-tissue-sparing thresholds can be easily achieved, and the concentration of specific radicals, thought to play a role in the FLASH process, can be manipulated (see, for instance, [117]). Using active control of the individual pulses ensures safe dosing. While not widely known to the medical community, existing systems have been used as 10s of MeV, kiloampere electron, or ampere level hadron sources since the 1960s [118].  
A key demonstrated capability of the technology is that the beam pipe can be made arbitrarily large without affecting the acceleration gradient [119,120]. This property enables independently controllable, multibeam acceleration through a single accelerator structure for complimentary irradiation. While the gradient of older induction linacs is low (\(<\)1 MV/m for 50-70 ns pulses), modern approaches enable 5-10 MV/m gradients. Thus, a 16 MeV system with four to eight or more individual beams with variable energy and pulse rate would fit in a clinic-sized vault of \(\sim\)100 m\({}^{3}\).  
Figure 11 depicts an artist's conception of a four-beam system; added beams are easily implemented [121]. The accelerator cells can be seen beyond the patient and patient couch. Four separate electron beams are being accelerated away from the patient, captured, and then bent 180\({}^{\circ}\) with two 90\({}^{\circ}\) dipoles. Solenoid transport is then used to return the beam alongside the patient, and a third 90\({}^{\circ}\) dipole directs the beam to a target where it is converted to bremsstrahlung. Multi-leaf collimators (MLC) can be used in this region for conformal therapy.