Radiation track-structure and nanodosimetry for treatment planning

Nanodosimetry

It is concerned with measuring ionization track structure down to nanometric resolution, a scale comparable to the dimension of DNA base pairs. Nanodosimetry relationship with the biological effect of ionizing radiation relies on two postulates (Grosswendt 2005, Rabus & Nettelbeck 2011).

•Postulate 1. The probability to produce a SSB in a short segment of DNA is expected to be proportional to the probability of obtaining an ionization cluster size of one.

•Postulate 2. As each relevant interaction is expected to occur with a probability proportional to that for an ionization, the overall probability for at least two relevant interactions (DSB) should also be proportional to the cumulative probability F2 for having ionization cluster sizes of two or more.

The simulation of ionization tracks at nanoscale demands much longer computation times compared to the so-called Condensed-History Monte Carlo. Our group had developed variance reduction techniques to improve the computational efficiency in Geant4-DNA and TOPAS-nBio.

AlphaTrackStructure
Ionization track segment (250 nm length) of 0.5 MeV/u alpha particle interacting in water.

Clinical translation of nanodosimetric quantities.

There have long been indications that the biological consequences of ionizing damage are determined primarily by the complexity of ionization detail at the level of DNA (Goodhead 1994). It seems reasonable to hypothesize that there exist nanodosimetric quantities that best correlate with radiobiological endpoints that those obtained on top of deterministic radiation descriptors (e.g., LET). Our group works (Prof. Bruce Faddegon, PI) in the characterization with MC of the spatial distribution of energy transfer locations at the nanoscale, its correlation with biological endpoints, and with a formalism to transfer that knowledge for treatment planning optimization. 

 

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