An investigation of nanodosimetric parameters for realistic geometries and a novel study of the track structure Penumbra region
Date
2021
Authors
Ngcezu, Sonwabile
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Abstract
Relative Biological Effectiveness (RBE) used in radiotherapy can be derived from
the study of nanodosimetric parameters of particle track structure (TS). In
nanodosimetry, the ionization component of charged particle TS is characterized by
the measurement or calculation of the frequency distribution of ionizations in target
volumes that are used to simulate nanometric sites in liquid water. In the current
study, Monte Carlo simulation tools and software analysis techniques are employed
in the mapping of nanodosimetric parameters radially from and along proton tracks.
Two approaches were used to study the radial dependence of nanodosimetric
quantities around protons tracks. A heuristic approach was ultimately used to
evaluate changes along the track pathlength, and secondly, a more accurate
approach was used to provide a detailed analysis of both the core and penumbra
regions. For the first approach, a nanodosimetric TS analysis attempt is presented
to address the issue of RBE variation in a Spread-Out Bragg Peak (SOBP) of
protons. The Geant4-DNA simulation package is used for the simulation and
capture of the ionization component of protons of 100 MeV initial energy and their
secondary electrons propagating in water. The frequency distribution of ionization
clusters formed in target volumes corresponding to a 10 base-pairs segment of
Deoxyribonucleic Acid (DNA) was obtained as a function of the radial distance
between target and proton trajectory for a set of positions along the proton path.
The radial dependence of nanodosimetric parameters was analyzed using a heuristic
model function to obtain an Effective Track Cross-Section (ETCS) derived from
the integration of the model as a function of the proton’s residual range. The results
were convolved with weighted range distributions suggested in the literature for the
construction of the SOBP. In the second approach, a more detailed investigation
into the nanodosimetric properties of the track structure of protons in water at
energies relevant for proton radiotherapy follows from the heuristic study above.
The ionization component of the tracks is still simulated using Geant4-DNA for
proton start energies between 1 MeV and 100 MeV. From the simulation results,
the frequency distribution of ionization clusters formed in nanometric target
volumes was obtained dependent on the impact parameter of the proton trajectory
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with respect to the target centre. In the track core, targets of cylindrical shape and a
size comparable to a short segment of DNA were used for scoring ionization cluster
size distributions. For the penumbra region, three different options for defining the
cylinder shell segments were investigated, with each cylinder shell segment volume
the same as the cylinder target volume. The radial distributions were numerically
integrated to obtain the effective track cross-sections with respect to different
nanodosimetric parameters. Graphically displaying the radial dependence in a
similar way as microdosimetric distributions allowed elucidating the contribution
of different radial distances to the overall radial integral of the quantities under
consideration. Furthermore, it was tested how well the radial dependence of the
nanodosimetric parameters could be fitted with a model function derived in
literature for the radial energy deposition in proton tracks.
The calculated ionization cluster size distribution from charged particle radiation
tracks depend heavily on the size, geometry, and material of the target volume. The
geometry of the target, specifically its orientation relative to the direction of the
primary track, is investigated in this study. Simulations performed in the first
approach are used to investigate the dependence of nanodosimetric parameters on
target orientation.
A related investigation involved the ion counter nanodosimeter at the Physikalisch
Technische Bundesanstalt (PTB), where both the electrical field and the extraction
aperture define the size and shape of the sensitive volume. In this study, a procedure
to determine a cylindrical effective measurement target that is based on the second
moments of the detection efficiency map is presented. The efficiency map is
represented by an analytical model used in the investigation of the dependence of
the simulated site size on the nanodosimeter’s operating parameters.
The ETCS derived from the heuristic model shows an increase in the distal end
region of the SOBP in qualitative agreement with radiobiological observations of
enhanced cell damage in this region. The results demonstrate that nanodosimetric
track characteristics may be used for qualitatively predicting the variation of the
probability for induction of lethal lesions in cells.
In the second approach, it was found that the model function from literature allows
describing only the radial dependence of the total frequency of nanometric targets
where ionizations occur. The deviation from a 1⁄���� dependence of the radial
dependence of the frequency of targets receiving more than a minimum number of
ionizations (exceeding one) includes a second peak centred around 10 nm radial
distance from the proton trajectory. Calculated nanodosimetric parameters are
found to have some dependence on the orientation of the target. With respect to the
investigation for the derivation of the wall-less target in a nanodosimeter, the results
show that within the limits of the simplifying assumptions, the model of an effective
cylindrical target gives a reasonable approximation of the efficiency map.
Description
A thesis submitted in fulfilment of the
requirements for the degree of Doctor of Philosophy to the Faculty of Science, University of
the Witwatersrand, 2021