Microdosimetry and Its Applications

In its action on matter, including living matter, ionizing radiation is uniquely efficient because it transfers energy to atoms in a highly concentrated form. The average energy absorbed per unit mass of irradiated medium, the absorbed dose, is minute compared to the energy densities that elicit comparable effects by other physical agents. The effectiveness of ionizations is further enhanced by their association in the tracks of charged particles. Depending on its microscopic distribution the energy required for a given level of biological injury may vary as much as a hundredfold between different ionizing radiations. Thus while the absorbed dose is a useful and standard quantity in the specification of irradiation, effects depend on the pattern in which a given amount of energy is deposited in the irradiated medium. A knowledge of such energy distributions is required not only in any explanations of the relative effectiveness of different kinds of ionizing radiation but it also can be expected to provide insight into the action of ionizing radiation in general. This has been recognized since the earliest days of radiobiology and led to the fundamental contributions by such investigators as Crowther, Dessauer, Timofeff-Resowsky, Zirkle and Lea.

The principal microdosimetric quantities: specific energy, z, and lineal energy, y, have been referred to in Sect. I.3. The formal definitions by the International Commission on Radiation Units and Measurements (ICRU, 1980) are:

As already described, regional microdosimetry is concerned with the stochastics of energy deposition in specified sites. Once the target is defined as a physical ensemble (composition, geometry, etc) the problem is reduced to studying the probability of interaction of particles with the target system — an exercise in quantum mechanics.

In the application of microdosimetry to radiation biology a distinction needs to be made between direct and indirect effects (see section VI.1.5.2). In the case of direct effect of radiation the spatial pattern of altered target molecules is expected to coincide with that of the initial energy deposits⁴⁴. In contrast, indirect action depends not only on the initial microdosimetric distribution (as represented, for example, by the radical species generated by radiation in the medium surrounding the target) but also on the probability that radicals that survive interactions among themselves diffuse and collide with the target molecule. Clearly the pattern of molecules modified indirectly is time dependent and not identical to that of the initial track. The qualitative features of these changes are illustrated in Fig.VII.1: the four panels (Turner et al, 1983) correspond to “snapshots” of the track of a 4 keV electron taken at times ranging from 1 psec to 0.1 μsec following passage through liquid water. During this time interval more than half of the initial radical species have reacted among themselves or have been converted to unreactive molecules; and one also notes the increasingly diffuse appearance of the track — in effect a decrease in the energy density of the track. Target molecules damaged indirectly by the track will have a spatial distribution that mimics the appearance of the track at the time of the reaction. This has important biological consequences: For instance, double strand breaks (dsb) in DNA result from the pairwise combination of single strand breaks (ssb) whenever they are within approximately 10 base pairs⁴⁵. The relative distance between ssb-s produced in indirect action depends in turn on the pattern of hydroxyl radicals, OH, assumed to be the main species attacking the DNA molecule. In a medium containing scavengers of OH radicals — as is usually the case intracellularly — only OH radicals within several nanometers of the DNA may yield ssb-s; the others would have been scavenged earlier. Because of this the time available for diffusion is only several nanoseconds and, paradoxically, in the presence of a scavenger the probability of induced ssb-s to yield dsb-s is larger (compare second and fourth panels in Fig.VII.1). It has been hypothesized also that the spatial proximity of damaged targets may affect their chance of being enzymatically repaired in the cell.