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Nanodosimetric characterisation of the track structure of protons in a spread-out Bragg peak

20.12.2019

Within the scope of the BioQuaRT project [1], a simple relation between the nanodosimetric properties of the particle track structure and cell inactivation was found [2]. For the potential use in clinical situations, options were investigated to transfer nanodosimetric results for individual targets to the voxel level [3]. The problem of the variation of the relative biological effectiveness (RBE) in a so-called spread-out Bragg peak (SOBP) of protons was also investigated on the basis of a nanodosimetric track structure analysis [4].

The Geant4-DNA toolkit was used to simulate ionisation track structure of 100 MeV protons in water. The frequency distribution of ionisation clusters formed in target volumes corresponding to a 10-base-pair DNA segment was obtained as a function of the radial distance between the target volume and the proton trajectory for a set of positions along the proton path. The radial dependencies of the complementary cumulative probabilities F1, F2, F3 and F4 for the production of at least 1, 2, 3 or 4 ionisations in the target volume were numerically integrated to obtain probability area products, or effective track cross sections (ETCSs), as a function of the proton's residual range. The results were then used to construct a SOBP for the absorbed energy dose, and subsequently, to generate the nanodosimetric equivalents of a SOBP from simulated range distributions.

 

 

Figure 1: Relative variation of the effective area integrals of the nanodosimetric cumulative probabilities F2 to F4 for a range distribution leading to a constant area integral of absorbed energy along a proton SOBP. The maximum initial proton energy was 100 MeV and the relative width of the SOBP was 25 % of the maximum range. The right-hand side of the plot shows a close-up of the SOBP peak region. All curves have been normalised to their respective value at a path length of 60 mm. The area integral of the absorbed energy dose is also shown (black line).

The radial dependence of the formation of ionization clusters in the so-called penumbra of the ionization track shows a transition from an inverse power law to an exponential behaviour at the track's end. The ETCSs show an increase in the range of the distal edge of the proton SOBP, which is in qualitative agreement with the radiobiological observations of increased cell damage within this region (Fig. 1).

The results demonstrate that nanodosimetric track structure characteristics may be used for qualitatively predicting the variation of the probability for the induction of lethal radiation damage in biological cells. This work will be furthered to determine whether the use of not only different target volume sizes, but also correlations between target volumes, can be used to obtain a quantitative prediction. 

Literature

(1)   H. Palmans, H. Rabus, A. L. Belchior, M. U. Bug, S. Galer, U. Giesen, G. Hilgers, D. Moro, H. Nettelbeck, M. Pinto, A. Pola, S. Pszona, G. Schettino, P. H. G. Sharpe, P. Teles, C. Villagrasa, J. J. Wilkens: Future development of biologically relevant dosimetry; Br. J. Radiology 88: 20140392 (2015)

(2)   V. Conte, A. Selva, P. Colautti, G. Hilgers, H. Rabus: Track structure characterization and its link to radiobiology; Radiat. Meas. 106, 506-511 (2017)

(3)   F. Alexander, C. Villagrasa, H. Rabus, J. J. Wilkens: Local weighting of nanometric track structure properties in macroscopic voxel geometries for particle beam treatment planning; Phys. Med. Biol. 60, 9145–9156 (2015)

(4)   H. Rabus, S. A. Ngcezu, T. Braunroth, H. Nettelbeck: “Broadscale” nanodosimetry: Nanodosimetric track structure quantities increase at distal edge of spread-out proton Bragg peaks; Rad. Phys. Chem. 168, 108514 (2020)

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