## 3 Synchrotron-Generated Novel RT Modalities  
### Microbeam Radiation Therapy (MRT)  
Biomedical beamlines at synchrotrons can generate both uniform (broad beam, BB) radiation fields as well as spatially fractionated fields (Figure 1). The radiation field can be spatially fractionated by adding a multislit collimator to the beam path. This generates an array of planar X-ray microbeams, typically only tens of \(\upmu\)m thick, separated by gaps of a few hundred \(\upmu\)m [8]. This array of microbeams is known as MRT and is used to target tumors in animal models. MRT shows significant promise for increased tumor control and reduced normal tissue damage compared to conventional RT. Synchrotrons can generate such high dose rate X-ray microbeams with physical properties superior to conventional sources [9].  
The MRT collimator normally produces planar microbeams of 25 or 50 \(\upmu\)m thick spaced by 200 or 400 \(\upmu\)m center-to-center in the horizontal dimension. In the vertical dimension, the microbeam array is just a few mm high (between 0.3 to 1.5 mm). However, this can be extended by using the goniometer stage to scan the sample vertically through the beam, and thus extending the microbeam array several cm. The multislit collimator then generates a heterogenous dose distribution, where hundreds of Gy are delivered directly by the microbeams (\"peak doses\") with regions between them receiving low-dose scatter irradiation (\"valley dose\"). However, this heterogeneous dose distribution depends on factors such as the energy spectra inherent to the synchrotron facility:  
* The main clinical research focus at the IMBL, AS, are RT and imaging. Imaging can be performed in an energy range of 15-150 KeV, while radiotherapy can be performed in an energy range of 30-120 KeV and with dose rates close to 1000 Gy/s [10]. The radiation source of MRT is a wiggler with a peak magnetic field of 4.2 T [11]. Starting from a storage ring current of 200 mA, a standard MRT spectral configuration can be delivered in 300 Gy/s by setting the wiggler to 3 T, which produces a spectrum with an average energy of 94 KeV and a peak energy of 87 KeV. Another MRT configuration can deliver 991.7 Gy/s by setting the wiggler to 4 T, with similar spectra as above (93 KeV on average) [12].
* The ESRF's beamline ID17 is also intended for medical imaging and RT studies. The radiation used for MRT comes from a wiggler of 1.5 m in length and a magnetic field of 1.6 T at a gap of 24.8 mm. The X-ray beam produced by the wiggler then continues for 37 m until it is attenuated to produce one of three different spectral configurations:  
Figure 1: Synchrotron can generate both broad beams and microbeams. (**a**) Broad beam synchrotron RT is a type of conventional RT which uses spatially uniform dose distribution. (**b**) MRT has a heterogeneous dose distribution with ablative peak and low valley doses. Typical beam dimensions used in the AS experiments are described below.  
(i) the standard MRT configuration used for rodent experiments for many years has an average energy of 104.2 KeV and a peak energy of 87.7 keV, (ii) the preclinical MRT configuration developed for veterinary trials and has a mean energy of 119 KeV and a peak energy of 102.1 KeV, and/or (iii) the clinical MRT configuration for future clinical applications with a mean energy of 122.8 KeV and a peak energy of 108.2 KeV [3, 13].  
Synchrotron radiation is required for MRT because: (i) the minimal beam divergence maintains the microbeam geometry at the microscopic level, (ii) the X-ray energy spectrum of 80-150 keV minimizes the range of secondary electrons that make an important contribution to the valley dose, and (iii) the ultra-high dose rates avoid beam smearing due to the cardiovascular movement [14]. The use of ultra-high dose rates has another advantage, namely the reduced radiation toxicity of normal tissue due to the rapid irradiation. This phenomenon is called the FLASH effect and is considered one of the most promising recent advances in radiation oncology.