Microdosimetry of electron microbeams

Track structures of 25, 50 and 80 keV primary electrons, simulated by the detailed-history Monte Carlo method, were analyzed for the frequency distributions of energy deposited in spheres with a diameter of 1 microm, placed in a cylindrically symmetrical array around the projected initial direction of the primary electron. The frequency mean of specific energy, the dose mean of lineal energy, and the parameters of lognormal functions fit to the dose distributions were calculated as a function of beam penetration and radial distance from the projected beam axis. Given these data, the stochastics of dose and radiation quality for micrometer-scale sites targeted by a medium-energy electron microbeam can be predicted as a function of the site's location relative to the beam entry point.     

Gamma densitometry for the measurement of skeletal density

A method is described for the measurement of the density of calcium carbonate materials from the attenuation of a narrow, collimated beam of gamma photons. For the measurement of density for slices, approximately 0.5 to 1.0 cm thick, from the skeletons of reef building corals, the optimum beam energy is 30–34 keV; and measurement is practical from approximately 22 to 100 keV. The potential utilities of five commercially available isotopic sources (¹⁰⁹Cd,¹²⁵I,²⁵³Gd,²¹⁰Pb and²⁴¹Am) are evaluated. Methods and results are presented for gamma densitometry using²¹⁰Pb and²⁴¹Am. The²¹⁰Pb point source had its principal gamma emission at 46.5 keV. Bremsstrahlung and high energy (800 keV) gamma emissions associated with the²¹⁰Pb decay grand-daughter were detected, and procedures were developed to accommodate the contribution of these emissions to the overall count rate. The attenuation of count rate by aluminium and aragonite absorbers closely followed simple theoretical considerations provided that narrow energy window settings were used at the radiation monitor. These theoretical considerations take account of the density of the material absorbing the radiation, and hence the density could be determined from the attenuation of the gamma beam. Increased accuracy was achieved by the use of²⁴¹Am and high speed counting equipment.²⁴¹Am has its principal gamma emission at 59.6 keV. The attenuation of this gamma beam follows simple theoretical considerations for targets with mass thicknesses from 0 to 6 g cm^-2. Aragonite from the shell of a giant clam was found to have slightly different properties in the absorption of gamma photons to aragonite from a coral skeleton. The differences were small but statistically significant.     

Experimental study of the evaporation and expansion of a solid pellet in a plasma heated by an electron beam

Results are presented from experiments on the injection of solid pellets into a plasma heated by an electron beam in the GOL-3 device. For this purpose, two pellet injectors were installed in the device. The target plasma with a density of ～10¹⁵ cm^?3 was produced in a solenoid with a field of 4.8 T and was heated by a highpower electron beam with an electron energy of ～1 MeV, a duration of ～7 s, and a total energy of 120–150 kJ. Before heating, the pellet was injected into the center of the plasma column transversely to the magnetic field. The injection point was located at a distance of 6.5 or 2 m from the input magnetic mirror. Polyethylene pellets with a mass of 0.1–1 mg and lithium-deuteride pellets with a mass of 0.02–0.5 mg were used. A few microseconds after the electron beam starts to be injected into the plasma, a dense plasma bunch is formed. In the initial stage of expansion, the plasma bunch remains spherically symmetric. The plasma at the periphery of the bunch is then heated and becomes magnetized. Next, the dense plasma expands along the magnetic field with a velocity on the order of 300 km/s. A comparison of the measured parameters with calculations by a hydrodynamic model shows that, in order to provide such a high expansion velocity, the total energy density deposited in the pellet must be ～1 kJ/cm². This value substantially exceeds the energy density yielded by the target plasma; i.e., the energy is concentrated across the magnetic field onto a dense plasma bunch produced from the evaporated particle.     

Experimental study of the dynamics of neutron emission from the GOL-3 multimirror trap

In experiments on the plasma heating and confinement in the GOL-3 multimirror trap, a deuterium plasma with a density of ～10¹⁵ cm^?3 and an ion temperature of 1–2 keV is confined for more than 1 ms. The plasma is heated by a relativistic electron beam. The ion temperature, which was measured by independent methods, reached 1.5–2 keV after the beginning of the beam injection. Since such a fast ion heating cannot be explained by the classical energy transfer from electrons to ions through binary collisions, a theoretical model of collective energy transfer was proposed. In order to verify this model, a new diagnostics was designed to study the dynamics of neutron emission from an individual mirror cell of the multimirror trap during electron beam injection. Intense neutron bursts predicted by this model were detected experimentally. Periodic neutron flux modulation caused by the macroscopic plasma flow along the solenoid was observed. The revealed mechanism of fast ion heating can be used to achieve fusion temperatures in the multimirror trap.     

Simulation of electron-beam irradiation of skin tissue model

Monte Carlo simulation of electrons stopping in liquid water was used to model the penetration and quality of electron-beam irradiation incident on the full-thickness EpiDerm? skin model (EpiDermFT? MatTek, Ashland, VA). This 3D tissue model has a fully developed basement membrane separating an epidermal layer of keratinocytes in various stages of differentiation from a dermal layer of fibroblasts embedded in collagen. The simulations were motivated by a desire to selectively expose the epidermal layer to low-linear energy transfer (LET) radiation in the presence of a nonirradiated dermal layer. The variable-energy electron microbeam at the Pacific Northwest National Laboratory (PNNL) was used as a model of device characteristics and irradiation geometry. At the highest beam energy available (90 keV), we estimate that no more than a few percent of the beam energy will be deposited in the dermal layer. Energy deposition spectra were calculated for 10-μm-thick layers near the 10th, 50th and 90th percentiles of penetration by the 90 keV electron beam. Bimodal spectra showed an increasing component of "stoppers" with increasing depth, which increases the probability of large energy deposition events. Nevertheless, screening by tissue above the layer of interest is the main factor determining energy deposited at a given depth.     

Low-LET microbeam investigation of the track-end dependence of electron-induced damage in normal human diploid fibroblasts

Using a pulsed electron beam, we investigated the dependence of micronucleus formation on the incident electron energy in AG01522 human diploid fibroblasts after nontargeted irradiations at 25 and 80 keV. Examining the dose response, we found that 25 keV electrons are more effective than 80 keV electrons at producing biological damage for a given dose. Our results demonstrating the induction of micronuclei as a function of incident electron energy offer direct support for the hypothesis that the electron track end is responsible for the biological damage occurring in the cell.     

The effect of attenuation map,scatter energy window width,and volume of interest on the calibration factor calculation in quantitative 177Lu SPECT imaging: Simulation and phantom study

PurposeThe objective of this study was to evaluate the image degrading factors in quantitative ¹⁷⁷Lu SPECT imaging when using both main gamma photopeak energies.MethodsPhantom measurements with two different vials containing various calibrated activities in air or water were performed to derive a mean calibration factor (CF) for large and small volumes of interest (VOIs). In addition, Monte Carlo simulations were utilized to investigate the effect of scatter energy window width, scatter correction method, such as effective scatter source estimation (ESSE) and triple energy window (TEW), and attenuation map on the quantification of ¹⁷⁷Lu. Results: The measured mean CF using large and small VOIs in water was 4.50 ± 0.80 and 4.80 ± 0.72 cps MBq⁻¹, respectively. Simulations showed a reference CF of 3.3 cps MBq⁻¹ for the water-filled phantom considering all photons excluding scattered events. By using the attenuation map generated for 190 keV photons, the calculated CFs for 113 keV and 208 keV are 10% lower than by using the weighted mean energy of 175 keV for ¹⁷⁷Lu. The calculated CF using the TEW correction was 17% higher than using the ESSE method for a water-filled phantom. However, our findings showed that an appropriate scatter window combination can reduce this difference between TEW and ESSE methods.ConclusionsThe present work implies that choosing a suitable width of scatter energy windows can reduce uncertainties in radioactivity quantification. It is suggested to generate the attenuation map at 113 keV and 208 keV, separately. Furthermore, using small VOIs is suggested in CF calculation.     

Low-dose studies of bystander cell killing with targeted soft X rays

The Gray Cancer Institute ultrasoft X-ray microprobe was used to quantify the bystander response of individual V79 cells exposed to a focused carbon K-shell (278 eV) X-ray beam. The ultrasoft X-ray microprobe is designed to precisely assess the biological response of individual cells irradiated in vitro with a very fine beam of low-energy photons. Characteristic CK X rays are generated by a focused beam of 10 keV electrons striking a graphite target. Circular diffraction gratings (i.e. zone plates) are then employed to focus the X-ray beam into a spot with a radius of 0.25 microm at the sample position. Using this microbeam technology, the correlation between the irradiated cells and their nonirradiated neighbors can be examined critically. The survival response of V79 cells irradiated with a CK X-ray beam was measured in the 0-2-Gy dose range. The response when all cells were irradiated was compared to that obtained when only a single cell was exposed. The cell survival data exhibit a linear-quadratic response when all cells were targeted (with evidence for hypersensitivity at low doses). When only a single cell was targeted within the population, 10% cell killing was measured. In contrast to the binary bystander behavior reported by many other investigations, the effect detected was initially dependent on dose (<200 mGy) and then reached a plateau (>200 mGy). In the low-dose region (<200 mGy), the response after irradiation of a single cell was not significantly different from that when all cells were exposed to radiation. Damaged cells were distributed uniformly over the area of the dish scanned (approximately 25 mm2). However, critical analysis of the distance of the damaged, unirradiated cells from other damaged cells revealed the presence of clusters of damaged cells produced under bystander conditions.     

MCNP5 evaluation of dose dissipation in tissue-like media exposed to low-energy monoenergetic X-ray microbeam

Following a significant increase in the number of facilities in the world having and developing low- and high-linear energy transfer (LET) microbeams for experimental radiobiological studies, it is useful and demanding to establish reliable computational models to analyze such experiments. This paper summarizes initial MCNP5 calculations of the basic parameters needed to study X-ray microbeam penetration, dose deposition and dose spatial dissipation in tissue-like media of micro and macro scales. The presented models can be used to predict doses delivered to neighboring cells and analyze the cause of bystander cell deaths. In the case of low-LET radiation, dose distribution is more homogenized when compared to high-LET that deposits almost all of its energy in the cell hit by radiation. Results are presented for a microbeam of monoenergetic soft (2–10 keV) X-rays for two different micro-models: (a) single-cells of homogeneous and uniform chemical compositions, and (b) single-cells of heterogeneous structures (nucleus and cytoplasm) with different chemical compositions. In both numerical models, only one cell is irradiated and the electron and X-ray doses in all cells are recorded. It was found that surrounding cells receive approximately five orders of magnitude less dose than the target cell in the homogenized cell model. The more detailed, heterogeneous model showed that the nucleus of the target cell receives more than 95% of the dose delivered to the entire cell, while neighboring cell nuclei receive approximately 65% of their total cell dose. Results of the macroscopic behavior of a soft X-ray microbeam using a cylindrical phantom 5 cm tall and 1 cm in diameter are also presented. Three-dimensional dose profiles indicate the spatial dose dissipation. For example, a 10 keV X-ray microbeam dose scatters to a negligible level at 0.3 cm radially from the center while it reaches an axial depth of 2 cm.     

Whole-cell imaging at nanometer resolutions using fast and slow focused helium ions

Observations of the interior structure of cells and subcellular organelles are important steps in unraveling organelle functions. Microscopy using helium ions can play a major role in both surface and subcellular imaging because it can provide subnanometer resolutions at the cell surface for slow helium ions, and fast helium ions can penetrate cells without a significant loss of resolution. Slow (e.g., 10–50 keV) helium ion beams can now be focused to subnanometer dimensions (∼0.25 nm), and keV helium ion microscopy can be used to image the surfaces of cells at high resolutions. Because of the ease of neutralizing the sample charge using a flood electron beam, surface charging effects are minimal and therefore cell surfaces can be imaged without the need for a conducting metallic coating. Fast (MeV) helium ions maintain a straight path as they pass through a cell. Along the ion trajectory, the helium ion undergoes multiple electron collisions, and for each collision a small amount of energy is lost to the scattered electron. By measuring the total energy loss of each MeV helium ion as it passes through the cell, we can construct an energy-loss image that is representative of the mass distribution of the cell. This work paves the way to use ions for whole-cell investigations at nanometer resolutions through structural, elemental (via nuclear elastic backscattering), and fluorescence (via ion induced fluorescence) imaging.     

Runaway electron beams in the gas discharge for UV nitrogen laser excitation

The review of the methods for obtaining the runaway electron beams in the gas discharge is performed. The new method is offered, using which the beam is first formed in a narrow gap (∼1 mm) between the cathode and the grid and then it is accelerated by the field of the plasma column of the anomalous self-sustained discharge in the main gap (10–20 mm long). The electron beams with an energy of about 10 keV and current density of 10³ A/cm² at a molecular nitrogen pressure of up to 100 Torr have been obtained experimentally. The results of research of the UV nitrogen laser with an excitation via runaway electron beam and radiation of energy of ∼1 mJ are given. The UV nitrogen laser generation with the energy of ∼1 mJ has been obtained by the runaway electron beams.     

Magnetic field excitation during electron beam injection from the Intercosmos-25 satellite (APEX)

Results of active experiments on electron beam injection from the Intercosmos-25 satellite into the ionospheric plasma are presented. A quasistatic magnetic field and the VLF-wave magnetic component are excited when an unmodulated electron beam with a current of I _be ?0.1 A and energy of ? _be =mv ²/2?10 keV is injected into the ambient plasma. The magnetic field excitation is attributed to the onset of plasma gradient instabilities.     

Ultrahigh charging of dust grains by the beam−plasma method for creating a compact neutron source

Generation of high-voltage high-current electron beams in a low-pressure (P = 0.1–1 Torr) gas discharge is studied experimentally as a function of the discharge voltage and the sort and pressure of the plasma-forming gas. The density of the plasma formed by a high-current electron beam is measured. Experiments on ultrahigh charging of targets exposed to a pulsed electron beam with an energy of up to 25 keV, an electron current density of higher than 1 A/cm², a pulse duration of up to 1 μs, and a repetition rate of up to 1 kHz are described. A numerical model of ultrahigh charging of dust grains exposed to a high-energy electron beam is developed. The formation of high-energy positive ions in the field of negatively charged plane and spherical targets is calculated. The calculations performed for a pulse-periodic mode demonstrate the possibility of achieving neutron yields of higher than 10⁶ s^–1 cm^–2 in the case of a plane target and about 10⁹ s^–1 in the case of 10³ spherical targets, each with a radius of 250 μm.     

Monte Carlo simulation of the spatial distribution of energy deposition for an electron microbeam

Dosimetry calculations characterizing the spatial variation of the energy deposited by the slowing and stopping of energetic electrons are reported and compared with experimental measurements from an electron microbeam facility. The computations involve event-by-event, detailed-histories Monte Carlo simulations of low-energy electrons interacting in water vapor. Simulations of electron tracks with starting energies from 30 to 80 keV are used to determine energy deposition distributions in thin cylindrical rings as a function of penetration and radial distance from a beam source. Experimental measurements of the spatial distribution of an electron microbeam in air show general agreement with the density-scaled simulation results for water vapor at these energies, yielding increased confidence in the predictions of Monte Carlo track-structure simulations for applications of the microbeam as a single-cell irradiator.     

Effects of Ultraviolet and X-Ray Radiation on in vitro Cultivated Cells of Haplopappus gracilis

A cell strain of Haplopappus gracills was used for investigations of the effects of UV (2537 A) and X-ray irradiation. Mitotic inhibition and killing after UV exposure were studied. A survival curve of UV treated and then plated cells is presented. The LD₅₀ seems to be about 2000 erg. mm^?2 under the experimental conditions used. All types of chromosome aberrations are induced by UV irradiation, but the frequency is relatively low at doses which do not completely inhibit cell division. A mutant strain of chromosome type is isolated after UV treatment and then plating. Mitotic inhibition and killing after X-ray treatment were studied. A survival curve is presented and the LD₅₀ under the culture conditions used seems to be about 2000 R. The frequency of chromosome aberrations induced by X-rays is highly increased by aeration during X-ray treatment which indicates that some degree of cell anoxia exists in a cell suspension. There arr indications that chromosome aherrations may not cause growth inhibition to such an extent as is usually believed.     

Distribution of Silicified Cells in the Leaf Blades of Pleioblastus chino(Franchet et Savatier) Makino (Bambusoideae)

Distribution of silicified cells in the leaf blades of Pleioblastuschino was investigated using a light microscope and a scanningelectron microscope equipped with an energy dispersive X-raymicroanalyser. The most dense accumulation of silica was foundin epidermal tissues. Little silica was deposited in vascularbundles and chlorenchyma, while more was deposited in bundlesheath and fusoid cells. In the epidermis, silica density andfrequency of silicified cells differed depending on cell type,although silica deposition was observed in most cell types.Heavy deposition was found in silica cells, bulliform cells,micro hairs and prickle hairs. Silica cells were the cell typemost frequently silicified (96.9–99.7%) in the adaxialand abaxial epidermis. Silica may be deposited as leaf tissuesage.Copyright 2000 Annals of Botany Company Pleioblastus chino(Franchet et Savatier) Makino, bamboo, silicified cells, leaf blade, epidermis, chlorenchyma, silica, clearing method, freeze-fracturing, freeze-drying, light microscopy, scanning electron microscopy, X-ray microanalysis     

Osteogenesis in cultures of limb mesenchymal cells

The results of previous reports demonstrated that osteoblasts develop in cultures derived from phenotypically unexpressive stage 24 chick limb mesenchymal cells. The observations reported here suggest that initial cell plating densities may provide environmental conditions deterministic to a particular limb phenotype. Quantitative microscopic studies, histochemical localization of calcium phosphate, and electron microscopy indicate that osteoblasts develop in cultures derived from stage 24 limb mesenchymal cells. Additionally, 1–3% of the cells from stage 24 limbs are associated with mineral deposits when plated at initial high densities (5 × 10⁶ cells per 35-mm culture dish), while more than 50% of the cells are associated with cartilage by Day 9. Cultures plated at intermediate seeding densities (between 2.0 and 2.5 × 10⁶ cells per 35-mm culture dish) have minimal cartilage development, and approximately 20% of the cells are associated with mineral by Day 9. Furthermore, cultures prepared from stage 31 limb mesenchymal cells form well-developed bone nodules with both osteoblasts and osteocytes present, but no cartilage. It is clear from these observations and from a consideration of the initiation of osteogenesisin vivo that the initiation of bone development in the limb is not associated with cartilage development. Based on these studies and observations on the effect of nutrient factors on phenotypic expression in culture, an hypothesis is presented relating differential vascularization and nutrient flow to the determination of limb phenotypesin vivo.     

Targeted irradiation of Mammalian cells using a heavy-ion microprobe

The existing focusing heavy-ion microprobe at the Gesellschaft für Schwerionenforschung in Darmstadt (Germany) has been modified to enable the targeted irradiation of single, selected cells with a defined number of ions. With this setup, ions in the range from helium to uranium with linear energy transfers (LETs) up to approximately 15,000 keV/microm can be positioned with a precision of a few micrometers in the nuclei of single cells that are growing in culture on a thin polypropylene film. To achieve this accuracy, the microbeam traverses a thin vacuum window with minimal scattering. Electron emission from that window is used for particle detection. The cells are kept in a specially designed dish that is mounted directly behind the vacuum window in a setup allowing the precise movement and the imaging of the sample with microscopic methods. The cells are located by an integrated software program that also controls the rapid deflection and switching of the beam. In this paper, the setup is described in detail together with the first experiments showing its performance. We describe the ability of the microprobe to reliably hit randomly positioned etched nuclear tracks in CR-39 with single ions as well as the ability to visualize the ion hits using immunofluorescence staining for 53BP1 as a marker of DNA damage in the targeted cell nuclei.     

On the eptihermal neutron energy limit for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT): Study and impact of new energy limits

Background and purpose: Accelerator-Based Boron Neutron Capture Therapy is a radiotherapy based on compact accelerator neutron sources requiring an epithermal neutron field for tumour irradiations. Neutrons of 10 keV are considered as the maximum optimised energy to treat deep-seated tumours. We investigated, by means of Monte Carlo simulations, the epithermal range from 10 eV to 10 keV in order to optimise the maximum epithermal neutron energy as a function of the tumour depth.Methods: A Snyder head phantom was simulated and mono-energetic neutrons with 4 different incident energies were used: 10 eV, 100 eV, 1 keV and 10 keV. ¹⁰B capture rates and absorbed dose composition on every tissue were calculated to describe and compare the effects of lowering the maximum epithermal energy. The Therapeutic Gain (TG) was estimated considering the whole brain volume.Results: For tumours seated at 4 cm depth, 10 eV, 100 eV and 1 keV neutrons provided respectively 54%, 36% and 18% increase on the TG compared to 10 keV neutrons. Neutrons with energies between 10 eV and 1 keV provided higher TG than 10 keV neutrons for tumours seated up to 6.4 cm depth inside the head. The size of the tumour does not change these results.Conclusions: Using lower epithermal energy neutrons for AB-BNCT tumour irradiation could improve treatment efficacy, delivering more therapeutic dose while reducing the dose in healthy tissues. This could lead to new Beam Shape Assembly designs in order to optimise the BNCT irradiation.     

Laser-generated plasmas at INFN-LNS

Hot plasmas can be generated by fast and intense laser pulses ablating solids placed in vacuum. A Nd:Yag laser operating at the fundamental and second harmonics with 9-ns pulses (maximum energy of 900 mJ) focused on metallic surfaces produces high ablation yields of the order of μg/pulse and dense plasma that expands adiabatically at supersonic velocity along the normal to the target surface. The plasma emits neutral and charged particles. Charge states up to 10+ have been measured in heavy elements ablated with intensities of the order of 10¹⁰ W/cm². The ion temperature of the plasma is evaluated from the ion energy distributions measured with an ion energy analyzer. The electron temperature is measured through Faraday cups placed at the end of long drift tubes by using time-of-flight technique. The neutral temperature is measured with a special mass quadrupole spectrometer placed along the normal to the target surface. The plasma temperature increases with the laser pulse intensity. The ion temperature reaches values of the order of 400 eV, the electron temperature is of the order of 1 keV for hot electrons and 0.1 eV for thermal electrons, and the neutral temperature is of the order of 200 eV. The experimental apparatus, the diagnostic techniques, and the procedures for the plasma temperature characterization will be presented and discussed in detail. Published in Russian in Fizika Plazmy, 2006, Vol. 32, No. 6, pp. 558–564. The text was submitted by the authors in English.