## 2 Beam Characteristics
### Beam Structure  
Existing proton therapy centers use one of three types of accelerator: an isochronous cyclotron, a synchrocyclotron, or a slow-cycling synchrotron [20]. The beam's time structure is different for each kind of accelerator, as summarized in Table 1. The main parameters describing the beam's time structure are acceleration RF frequency, length of a proton bunch, the width of a continuous pulse usable for treatment, and its repetition rate.  
Figure 1: Schematic picture of a proton therapy facility. We identify here the ‘upstream’ and ‘downstream’ beamlines that we will refer to in the text.  
In the case of isochronous cyclotrons, the extracted beam can be considered continuous, as RF frequencies of cyclotrons used for proton therapy are in the range of 50-100 MHz. As such, every 10-20 ns, a 1-2 ns long bunch is delivered. The beam continuity, combined with high beam intensities which existing cyclotrons can reach, makes an isochronous cyclotron appear to be the best candidate for potential FLASH proton therapy, unless the dose rate within the pulse is important.  
Synchrocyclotrons operate with similar RF frequencies, but the time structure of the extracted beam is significantly different. The RF frequency is decreased synchronously to the increasing revolution time at larger orbit radii. The RF does not vary very quickly; thus, the acceleration is slow and requires many turns up to extraction. The whole cycle is repeated with a frequency of up to 1 kHz. This means that the beam consists of short pulses (order of 1 \(\upmu\)s) repeated every 1-3 ms. As such, the use of synchrocyclotrons for FLASH irradiation seems to be challenging and might require some adaptations. For instance, a clinical Mevion HYPERSCAN(r) (Mevion Medical Systems, Littleton, MA, USA ) system was modified to deliver ultra-high dose rates for FLASH experiments [21]. One of the key changes was an increased pulse width to 20 \(\upmu\)s. As such, an average dose rate of up to 200 Gy/s was achieved. However, the pauses between pulses are still long (1.5 ms). As it is still not clear whether the instantaneous dose rate or average dose rate is the main driver of the FLASH protective effect, this unit represents a promising platform for further investigation of this aspect.  
Synchrotrons accelerate beam in cycles (spills), each including filling of the ring with bunches of protons, acceleration to a desired energy, extraction, and ramping down to the initial situation [22]. All the existing clinical machines are slow-cycling. This means the extraction is realized in multiple turns, which guarantees a continuous beam for 0.5-5 s with a constant intensity (on average). The treatment pulse for the same energy can be repeated after approximately 2 s. This represents one of several challenges to deploy synchrotrons for FLASH proton therapy [23]. Assuming sufficient intensity, which can be achieved with multi-turn injection, fast energy changes, and rapid extraction are needed. The base for these adaptations would be rapid-cycling synchrotrons. The use of synchrotron for experiments with cells have been recently reported [24]. Ultra-high dose rates up to 800 Gy/s were achieved by applying a high-frequency power dozens of times higher than usual to extract all protons within approximately 50 ms.  
The major challenge for online upstream beam monitoring is the total irradiation time. The beam instrumentation must have a suitable time resolution for online beam monitoring. For instance, a sampling rate of acquisition devices must be higher than 1 kHz, as single-fraction irradiation can be as short as 1 ms. For in-room diagnostics, other challenges also have to be taken into account, as discussed in Section 3.