Biomedical Engineering Reference
In-Depth Information
result of ionization and excitation of the medium [
3
-
5
], interaction of secondary
particles with biological molecules, most important with DNA [
1
,
2
], the analysis of
induced damage, and evaluation of probabilities of subsequent cell survival or death.
Evidently, this approach is interdisciplinary, since it is based on physics, chemistry,
and biology. Moreover, it spans several areas within each of these disciplines.
The multiscale approach started with the analysis of ion propagation, which
resulted in the description of the Bragg peak and the energy spectrum of secondary
electrons [
3
-
6
]. The practical goal of these works was providing a recipe for
economic calculation of the Bragg peak position and shape. Theoretically, they
concluded that the cross section of ionization of molecules of the medium singly-
differentiated with respect to the energies of secondary electrons is the most
important physical input on this scale, the longest in distance and highest in energy.
The relativistic effects play an important role in describing the position of the
Bragg peak as well as the excitation channel in inelastic interactions [
3
]. The
effect of charge transfer and projectile scattering affect its shape [
3
]. The effects
of nuclear fragmentation happening in the events of projectile collisions with the
nuclei of the medium are also important on this scale. The next scale in energy
and space is related to the transport of the secondaries, which has been considered
in Refs. [
1
,
7
], but it may still be revisited. The results of this analysis will give
the spatial distributions of secondary particles as well as the accurate radial dose
distribution.
The goal of the analysis of DNA damage mechanisms is the obtaining of the
effective cross sections for the dominant processes, which should be taken into
account in order to calculate the probability of different lesions caused by different
agents. The above three stages of processes, represent not only different spatial
scales, but also different time scales slowing from 10
21
to 10
5
seconds. We
would like to calculate the spatial distribution of primary DNA damage, defined
by the longest biochemical time, including the degree of complexity of this damage.
Then, the repair and other biological effects can be included and thus the relative
biological effectiveness (RBE) can be calculated. The RBE is one of the key
integral characteristics of the effect of ions compared to that of photons. This
ratio compares the doses of different projectiles leading to the same biological
result. The calculation of RBE using the multiscale approach will be a result of a
constructive quantitative analysis to physical, chemical, and biological phenomena
and its predictive power will be scientifically sound. Conditions or environment
related to the radiation damage may vary, if, e.g., the dose deposition is fast as in
laser-driven beams, chemically active components increasing the number of active
agents are present, or biological factors are more important, etc. The multiscale
approach capable of including these variations will be more versatile than the
existing approaches to calculating the RBE.
In [
7
], the radial dose distribution has been addressed. Traditionally, the radial
dose is related to the radial distribution of damage. However, this does not include
the complexity of damage, which may not be directly related to the dose. It is still
not clear how to relate the dose with complexity of damage. This work is a step in
this direction.
