Preclinical radiotherapy at the Australian Synchrotron's Imaging and Medical Beamline: instrumentation, dosimetry and a small-animal feasibility study

Abstract

Therapeutic applications of synchrotron X-rays such as microbeam (MRT) and minibeam (MBRT) radiation therapy promise significant advantages over conventional clinical techniques for some diseases if successfully transferred to clinical practice. Preclinical studies show clear evidence that a number of normal tissues in animal models display a tolerance to much higher doses from MRT compared with conventional radiotherapy. However, a wide spread in the parameters studied makes it difficult to make any conclusions about the associated tumour control or normal tissue complication probabilities. To facilitate more systematic and reproducible preclinical synchrotron radiotherapy studies, a dedicated preclinical station including small-animal irradiation stage was designed and installed at the Imaging and Medical Beamline (IMBL) at the Australian Synchrotron. The stage was characterized in terms of the accuracy and reliability of the vertical scanning speed, as this is the key variable in dose delivery. The measured speed was found to be within 1% of the nominal speed for the range of speeds measured by an interferometer. Furthermore, dose measurements confirm the expected relationship between speed and dose and show that the measured dose is independent of the scan direction. Important dosimetric parameters such as peak dose, valley dose, the collimator output factor and peak-to-valley dose ratio are presented for 5 mm × 5 mm, 10 mm × 10 mm and 20 mm × 20 mm field sizes. Finally, a feasibility study on three glioma-bearing rats was performed. MRT and MBRT doses were prescribed to achieve an average dose of 65 Gy in the target, and magnetic resonance imaging follow-up was performed at various time points after irradiation to follow the tumour volume. Although it is impossible to draw conclusions on the different treatments with such a small number of animals, the feasibility of end-to-end preclinical synchrotron radiotherapy studies using the IMBL preclinical stage is demonstrated.

Experimental optimisation of the X-ray energy in microbeam radiation therapy

“…This study was performed using the preclinical radiotherapy instrumentation in Hutch 2B of the Imaging and Medical Beamline (IMBL) at the Australian Synchrotron [29].…”

“…Microbeams are produced by a multislit collimator (Usinage et Nouvelles Technologies, Morbier, France), which collimates the beam into 125 vertical microbeams of 50 mm width with a 400 mm centre-tocentre (c-t-c) spacing [29]. Tungsten carbide layers of 350 mm are sandwiched together to create a 50 mm spacing between them.…”

“…The PVDR was calculated using the mean of the three peak doses and the mean of the doses in the central 100 μm of the two valleys. For a graphical representation of the points used to calculate the PVDR in an example profile exhibiting four peaks and three valleys, see §2.3 of [29]. The PVDR was measured for monochromatic energies between 40 and 120 keV at depths of 5, 10, 20 and 50 mm in a water tank.…”

Impact of cardiosynchronous brain pulsations on Monte Carlo calculated doses for synchrotron micro‐ and minibeam radiation therapy

“…These promising radiotherapy approaches are nowadays being explored at the European Synchrotron Radiation Facility (ESRF), the Brookhaven National Laboratory, and the Australian Synchrotron …”

“…These promising radiotherapy approaches are nowadays being explored at the European Synchrotron Radiation Facility (ESRF), 22 the Brookhaven National Laboratory, 8 and the Australian Synchrotron. 23 However, one of the most important limitations to exploit MRT and MBRT in brain tumor treatments may be the blurring of the dose distributions due to cardiosynchronous pulsations. As the maximum speed reached by the brain due to heartbeat is 2 mm/s, extremely high-dose rates are required to avoid the consequent beam smearing that would jeopardize the tissue sparing effect of the smallest microbeams.…”