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Specification of radiation quality at the namometer level

Objective

Description of research work
Research concerning the best way of specifying radiation quality for radiobiology and radiation protection by physical parameters expressing the relationship between track structure and target structure remains a central task of microdosimetry. Since both molecular biological and radiobiological analysis (track segment method) suggest critical target sizes of a few nanometres for cellular radiation effects, the imperfection of present microdosimetric simulation of volumes in the micrometre range have become evident. For all ionizing particles or particle configurations (eg Auger cascade) which produce a high concentration of deposited energy on the nanometer scale but having ranges much smaller than the micrometre dimensions, the spatial resolution of present microdosimetric detectors is inadequate. The project has four main aims.

Track structure studies for nanometre targets
The aim is to establish the approximated constancy of the delta ray contribution to the energy deposition fluctuation in a nanometre target. To establish the constancy of the radiation of restricted LET to linear primary ionization.

Biological validation of the best suited parameter
The aim is to select bench mark sets of survival, chromosome aberration and molecular lesion data to test and confirm the ability of linear primary ionization and restricted LET to determine their variation with radiation quality.

Experimental studies of associate detector systems
The aim is to measure the ionization pattern around charged particles tracks and study a portable device able to simulate T.E. volumes of few tens of nanometres in size.

Quantification of indirect action from single tracks
The aim is to conduct an experimental study of the yield and spatial distribution of paramagnetic free radicals formed in the wake of individual tracks by measurement of relaxation time and using the ESR technique; and to compare the experimental results with the predictions of a simplified theoretical model of biological effectiveness .
Research has been carried out in order to investigate the working characteristics of a cylindrical tissue equivalent plate chamber (TEPC) at very low pressures and to develop a gas counter able to measure the ionization pattern near the track of a charged particle at nanometre (nm) level.

The coordinated experiment aims to measure the ionization distributions as close as 20 nm, or less, to the track with enough spatial resolution to test the Monte-Carlo calculations which point out that the ionization distributions very close to the particle path are independent of the particle type and energy.

Gas detectors working in pulse mode can measure ionization distributions. The 2 experimental problems to solve are:
to measure 1 single electron;
to obtain the information on the initial position of the electron within a few nm uncertainty.

The diffusion of electrons in gas is related to the gas pressure (P) and the travelling path (X). By decreasing the gas pressure the detection precision of the single electron is improved even if the diffusion in the gas increases at low pressures, due to the fact that in this experiment the precision is related to simulated lengths.

In order to obtain a position uncertainty inside the nm range it is necessary to work at about 1 torr of pressure or less and with drift lengths of about 1 mm. The intention is to manufacture a track detector made up of 2 parts: the drift region and the multiplication region. The drift region is defined by 2 parallel plates a few mm apart; the charge particle crosses the drift region at selected lateral distances from 2 parallel to beam slits defining the ionization collecting region. The electrons produced in that region are made to drift into the multiplication region where they are detected.

The first track detector to be assembled will have a single wire cylindrical proportional counter as multiplication region.
The multiplication characteristics of the cylindrical proportional counter eq uipped with a 10 um anode have been measured in the propane based TE mixture at different pressures down to 22.7 Pa (0.17 torr), using an experimental set up modified in order to use low velocity ions as a probe. The results show that a drift region exists even at very low pressures. This finding assures the possibility of separating properly the drif and the avalanche region even if the grid, which will separate the 2 regions, is not able to completely confine the electrical field.

Limitaions to the conventional dosimetry instrumentation, currently used for control exposure in radiological protection and in radiation therapy, are directly traceable to lack of knowlwdge of the required response function for ionizing radition. Consequently modifying factors which are dependent on the type of radiation must be applied to the instrumental response if bioeffectivenesss is to be assessed. Recent rediation research has produced a concensus tha double stand breaks induces in the DNA of mammalian cells constitute the dominantly important lesions which lead to chromosome aberrations, oncogenic transformation and genetic mutation. The object of the research was to explore methods of obtaining physical deviceshaving a response which will simulate the yield of double strand breaks in DNA. A completely new generation of dosimeters is anticipated. Ideally the devices should be in the condensed phase with radiation sensors of nanometre dimensions. Arrrays of detectors are envisaged foe application in radiological protection.
Feasibility studies have been carried out and preliminary research is being conducted with various novel detectors based on MOSFET, Langmuir Blodgett films, thin film scintillators, miniature liquid filled proportional counters, etc.

A topologic study of the delta-ray escape from targets small in comparison with delta-ray ranges has brught a unique chance for microdosimetry to characterize radiation quality with a single radiophysical parameter when targets of nanometer dimensions are concerned. The biological establishment and physical generalization of this new and far-reaching observation are underway. Monte-Carlo histories of particle tracks projected upon cylindrical targets of various lengths and diameters in the nanometer range have been studied for electron and photon radiations as well as for protons and alpha particles, and the mean primary ionization density respectively the restricted linear energy transfer I Delta which is proportional to it for small small values of Delta was thereby further qualified as the single determinant of energy deposition fluctuation varying with the primary prticle. Restricted linear energy transfer (LET) is defined to exclude kinetic energies of delta-rays larger than Delta. The low cutoff energy Delta = 100 eV was chosen to secure this proportionality.

Proving this as a general regularity is underway, utilizing the fact that the invariability of the delta-ray fluctuation contribution for nanometer targets rests on the invariability of the low energy portion of the delta-ray spectrum, which is due to the physical regularities of glancing collisions.

The correlaton of various cellular effects with restricted LET is being investigated. A convincing linear dependence of yield coefficient alpha for dicentric chromosomes in human lymphocytes upon L100,D has been observed and is more and more confirmed by new experimental results. The Restricted LET dependence of other cellular and molecular radiation effects, which may lead to combined applications of L100,D and L100,T is under investigation.

The cross section data set for the Monte-Carlo simulation program has been extended to proton energies below 100 keV using analytical functions given by M E Rudd (Radiation Protection Dosimetry 31, 17-22, (1990)) for the ejection of secondary electrons from different shells in water vapour. By subtraction of the kinetic energy of the secondary electrons and the ionization potential energy from stopping power cross sections the excitation cross section was derived under the assumption of a mean excitation energy of 12.6 eV. The energy deposition by simulated proton tracks traversing spherical targets of 1 to 100 nm diameter was calculated for 10 to 100 keV. Below 10 nm straggling effects lead to asymmetric distributions.

The invariance of secondary electron track component with regard to proton energy for nanometer targets was analysed. The contribution of single secondary electron tracks to the dose meanlineal energy for nanometer targets over the proton energy range from 0.2 MeV up to 15 MeV was derived from the corresponding proximity function component. For 1 and 2 um targets only a small variation was seen. This indicates the postulated invariance.

An electron spin resonance (ESR) spectrometer was adaped to measure precisely the spin spin relaxation time by means of the determination of microwave field in the cavity.
Determination of the spin spin relaxation time by the method of saturation requires knowledge of the intensity of the field inside the cavity. The Slater method, originally developed for accelerators considers changes of the frequency of the cavity as a consequence of the introduction of a very small conducting sphere to the point where the sample is placed during ESR measurements. The metal sphere was mounted on a micropositioner and the measuring system was used to determine the necessary quantities. The intensity of the magnetic field was then found.

Local radical densities were determined in gamma ray irradiated samples of solid biochemicals as a function of imparted dose.
The average concentrations of radicals in the bulk of the solid matrix are found from the total absorbed dose and the intensity of ESR line. The procedure is lengthy, involving comparison of the unknown sample with the known amount of diphenylpicrylhydrazyl (DPPH) and the absolute values of yield were found with an uncertainty of at least +/- 8%.

In condensed media the electrons, released as a consequence of interaction of photons with medium, lose energy in the ionization regions: spurs, blobs, short tracks and principal tracks. The local radical density in spurs and blobs is of interest. The blobs have dimensions of an order of nanometers. The local radical concentration inside an ionization region does not increase with dose as measurements have confirmed for amino acids. Radiation doses of gamma rays from cobalt-60 Co have been used in the region of linear response because of the appearance of dose saturation signifies an overlap of spurs. The typical concentrations of radicals in amino acids are between 5 E19 to 2 E20 radicals per cm{3}. For 2-component and 3-component polyaminoacids the concentrations are about 50% smaller. Local radical densities were measured in some carbohydrates as well as in deoxyribonucleic acid (DNA) and some nucleosides. In order to arrive at the local spacing between radicals the volume of the trapping region within the spur must be known. This, can be estimated from the knowledge of energy deposited in a spur.

To assist in the measurements utilizing the Katsumura method of determining the degree of signal saturation, 2 computer programs were written, one calibrates the readout, eliminates the skew and smoothes the lineshape and the second obtains the product of spin spin and spin lattice times.
Track structure studies, based on computer simulation, recent cross section and adequate statistical concepts such as distribution parameters, pattern recognition and target modelling, will provide the physical basis for validation of the proposed quantities of linear primary ionization or restricted LET. The phenomenon of O-ray cutoff at nanometre target boundaries will need further study, and the proposed close correlation of these quantities with lineal energy in simulated nanometre volumes will have to be substantiated. The work will include recent cross sections and genomic target structure.

The ultimate decision concerning the suitability of the new radiation quality parameters must be provided by their ability to predict the dependence of radiobiological yields on radiation quality. This work, already started by the groups cooperating in promoting linear primary ionization or restricted LET, needs further effort in broadening the biological data base and stepping forward from retrospective analysis to a predictive approach.

The actual experimental studies, which aim to determine the lowest simulation limit of slow ions as probes to explore the avalanche characteristics of single wire and field grid TEPC. A tissue equivalent multistep parallel plate avalanche chamber will be manufactured to measure single ionizations in order to study the correlation between primary ionization and restricted LET. The possibility of manufacturing a small cylindrical avalanche chamber will be studied. In parallel with the gas filled detectors, a feasibility study will be carried out with the object of simulating the biological response to radiations in nanometre dimensions in condensed phase detectors. The optimum method will be selected, guided by the biological analysis, and work will begin on a device.

ESR measurements will be used to explore the spatial distribution, mean life times and reaction rates of free radicals generated by charged particle tracks in nucleic acids, proteins, amino acids from cell cultures and, possibly, whole tissues. Measurement of radical density is based upon the dependence of the saturation value of microwave magnetic fields upon the spin spin relaxation time. The possibility of adapting simplified theoretical methods, developed for enzyme inactivation by indirect action, will be explored in an attempt to obtain a more meaningful model of radiation action for radiation protection purposes.

Collaboration schedule
Although the collaborators will support each other mutually by the exchange of theoretical and experimental data, the collaboration main lines will be the following:
Gottingen-Neuherberg for the track studies;
St. Andrews-Gottingen for the biological validation;
Legnaro-St.Andrews-Neuherberg for the experimental studies;
Rome-St.Andrews for the interpretation of the indirect action studies.

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CSC - Cost-sharing contracts

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ISTITUTO NAZIONALE DI FISICA NUCLEARE
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Via Romea 4
35020 LEGNARO
Italy

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Last update: 21 October 1991

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Permalink: https://cordis.europa.eu/project/id/BI7*0040

European Union, 2024