Nanodosimetry – on the ''tracks'' of biological radiation effectiveness

Abstract

It is well known that the biological effectiveness of a certain absorbed dose of ionizing radiation depends on the radiation quality, i. e. the spectrum of ionizing particles and their energy distribution [1], [2], [3]. As has been shown in several studies, the biological effectiveness is related to the pattern of energy deposits on the microscopic scale, the socalled track structure [4]. Clusters of lesions in the DNA molecule within site sizes of few nanometers play a particular role in this context [4], [5], [6]. A first approach to measure track structure of ionizing radiation with nanometric resolution was proposed already in 1975 [7]. However, the extension of microdosimetric measurements to site sizes of few nanometer dimension was facing the fundamental problem that in such small sites the number of interactions is too low, such that the assumption fails that the imparted energy is the number of ionizations multiplied by a simple conversion factor [8]. Therefore, the development of methods for measuring track structure details with nanometric resolution required a change of paradigm, namely restricting the characterization of track structure to its ionization component [9], [10].In should be noted in this context that the term nanodosimetry is used in the literature in different meanings. These include ongoing endeavors to extend microdosimetry into the nanometer range to below 100 nm site sizes [11], [12] as well as simulation studies of various kinds that are not focused on quantities that are directly measurable. In this paper we use the term nanodosimetry for studies of charged particle track structure, considering the stochastics of ionizations in nanometric targets.The quantity of interest is the relative frequency distribution of the so-called ionization cluster size, i.e. the number of ionizations inside a considered target (often called the 'site'). As is illustrated in Figure 1, the ionization cluster size distribution (ICSD) varies with the geometrical position of the target with respect to the particle track. Furthermore, it also depends on the size and composition of the target and, most importantly, on the radiation quality. The ICSD can also be characterized by its statistical moments or the complementary cumulative frequencies of ionization clusters exceeding a certain minimum size [13].Around the turn of the century, three different types of nanodosimeters have been developed to measure the frequency distribution of ionization cluster size [14]. All devices are gas counters that simulate nanometric sensitive volumes based on a density scaling principle [15]. They Figure 1. Schematic illustration of nanodosimetric ionization cluster size (ICS) distributions in a spread-out Bragg peak (SOBP) of protons in water. The orange spheres indicate the loci of ionizing interactions of the proton or of the emitted secondary electrons. The blue and red cylinders represent nanometric targets located in the core and in the penumbra region of the track, respectively. The histograms with the blue and red...

First measurements of ionization cluster‐size distributions with a compact nanodosimeter

“…A common fundamental cause of biological effects is the productions of double-strand breaks which correlate with the probability to produce ionizations within a volume of 10 base pairs of DNA. [1][2][3][4] The nanodosimetric quantity, which is measured in a DNA-sized volume, is the number of ionizations ν produced by single traversing charged particles of specified radiation quality, which is described by a probability distribution PðνÞ.…”

“…The aim of nanodosimetry is to provide physical measurements of a quantity which describes biological effects of ionizing radiation better than conventional absorbed dose measurements. A common fundamental cause of biological effects is the productions of double‐strand breaks which correlate with the probability to produce ionizations within a volume of 10 base pairs of DNA 1–4 . The nanodosimetric quantity, which is measured in a DNA‐sized volume, is the number of ionizations produced by single traversing charged particles of specified radiation quality, which is described by a probability distribution .…”

Eurados Strategic Research Agenda 2020: Vision for the Dosimetry of Ionising Radiation

“…Develop multi-scale characterisation of track structure using nanodosemeters with multiscale measurement capabilities and track structure simulation codes ( 19 , 37 , 38 ) .…”

Investigation into the foundations of the track-event theory of cell survival and the radiation action model based on nanodosimetry

“…The derivation of eq. ( 9) did not require presuming the (multi-event) distributions of lethal events and sublethal events to be statistically independent and to be Poisson distributed as was done in previous work ( Besserer and Schneider 2015a, 2015b, Schneider et al 2016, 2020. Both properties follow from the assumption of the Poisson distribution of the number of primary tracks interacting with the cell.…”

“…If the ROI is the CV of Schneider et al ( 2020), W1(0) is the number of BIVs per CV. (Whereas Schneider et al ( 2019, 2020 used the ratio of mean chord length through the CV and BIV diameter for the number of BIV per CV that potentially receive an ionization cluster. )…”