Monte Carlo simulation of single-cell irradiation by an electron microbeam

A model is presented for irradiation of a cellular monolayer by an electron microbeam. Results are presented for two possible window designs, cells plated on the vacuum-isolation window and cells plated on Mylar above the vacuum-isolation window. Even for the thicker dual-membrane window that facilitates tissue culture and allows the target cell to be centered relative to the electron beam, the majority of the calculated beam spreading was contained in a volume typical of the mammalian HeLa cell line. None of the 10⁴ electrons simulated at 25 keV were scattered into the spatial region occupied by neighbors of the target cell. Dose leakage was largest at 50 keV where the mean energy deposited in all neighbors was 21% of that deposited in the target cell. This ratio was reduced to 5% at 90 keV, the highest beam energy simulated. Lineal energy spectra of energy deposition events scored in the nucleus of the target cell became progressively more like the gamma-ray spectrum as the electron beam energy increased. Hence, our simulations provide strong support for the feasibility of a low-LET, single-cell irradiator. Received: 16 March 2000 / Accepted: 9 May 2000     

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.     

A Monte Carlo simulation of Auger cascades

The energy imparted to biological tissue after the decay of incorporated Auger emitters stems from two sources: (a) energy deposition by the Auger and Coster-Kronig electrons and (b) the charge potential which remains on the multiple ionized atom after the end of the cascade. For the numerical assessment of both the kinetic energy of the released electrons and the charge potential, a new and--for purposes of microdosimetry--precise method is presented. Based on relativistic Dirac-Fock calculations and a rigorous bookkeeping, this method provides a perfect energy balance of the considered atomic system when applied to Monte Carlo simulations of Auger cascades. By comparing the results for charge distribution for krypton and iodine with experimental data and the electron spectrum of 125I with theoretical data, it can be shown that the approach followed in this work is reasonable and appropriate for the determination of the energy deposited by incorporated Auger emitters in small volumes of condensed matter. The total energy deposited by 125I in a volume of 20-nm diameter is 2.03 keV which is made up by multiple ionization (1.07 keV) and energy deposition by the emitted Auger electrons (0.96 keV).     

Electron beam patterning of biomolecules

The patterning of biomolecules on semiconducting surfaces is of central importance in the fabrication of novel biodevices. In the process of patterning, it is required that the biomolecule preserves its properties and the substrate is not damaged by the chemicals, the temperatures or the patterning beams involved in the procedure. Recently, both DUV and electron beam microlithography have been used in order to deposit protein layers in predefined patterns. Various approaches have been used, some involving photoresists. Contrast between exposed and unexposed regions, resolution of adjacent features and sensitivity to dose variation, are the key issues. The approach followed in this paper consists of a direct patterning of a biotin layer, deposited on an amino-silane primed silicon nitride surface, using an electron beam. After irradiation, the surface is covered by bovine serum albumin (BSA), which acts as a blocking material to protect the exposed areas from streptavidin adsorption. Using 20 keV e-beam energy and doses, in the range 100-1000 microC/cm(2), submicrometer dense lines of 1-microm pitch have been obtained. The results have been tested by fluorescence optical microscopy.     

人胎儿真皮乳头和皮纹发生的研究

本文用扫描电镜法研究了入胎儿的皮纹发生过程,包括初级真皮嵴、次级真皮嵴、真皮乳头和表皮隆线的发生。为研究人皮纹的发生和皮肤的异常提供了皮肤正常发育的形态学依据。共观察111例从第6周到第9个月胎儿的皮纹区皮肤,表明第3个月末胎儿开始形成初级真皮嵴,以后逐渐加深,至第16周嵴的顶端中央产生纵沟形成两条平行的次级真皮嵴;自19周后,次级真皮嵴局部隆起,由波浪形逐渐形成乳头。至30周乳头呈犬牙状。表皮隆线于第4—5月形成,随真皮乳头的增高而渐趋明显。至第6个月,全部皮纹图样已可辨认。本文还讨论了真皮乳头发生的过程。     

Experimental optimisation of the X-ray energy in microbeam radiation therapy

Microbeam radiation therapy has demonstrated superior normal tissue sparing properties compared to broadbeam radiation fields. The ratio of the microbeam peak dose to the valley dose (PVDR), which is dependent on the X-ray energy/spectrum and geometry, should be maximised for an optimal therapeutic ratio. Simulation studies in the literature report the optimal energy for MRT based on the PVDR. However, most of these studies have considered different microbeam geometries to that at the Imaging and Medical Beamline (50 μm beam width with a spacing of 400 μm). We present the first fully experimental investigation of the energy dependence of PVDR and microbeam penumbra. Using monochromatic X-ray energies in the range 40–120 keV the PVDR was shown to increase with increasing energy up to 100 keV before plateauing. PVDRs measured for pink beams were consistently higher than those for monochromatic energies similar or equivalent to the average energy of the spectrum. The highest PVDR was found for a pink beam average energy of 124 keV. Conversely, the microbeam penumbra decreased with increasing energy before plateauing for energies above 90 keV. The effect of bone on the PVDR was investigated at energies 60, 95 and 120 keV. At depths greater than 20 mm beyond the bone/water interface there was almost no effect on the PVDR. In conclusion, the optimal energy range for MRT at IMBL is 90–120 keV, however when considering the IMBL flux at different energies, a spectrum with 95 keV weighted average energy was found to be the best compromise.     

Ion beam radiobiology and cancer: Time to update ourselves

High-energy protons and carbon ions exhibit an inverse dose profile allowing for increased energy deposition with penetration depth. Additionally, heavier ions like carbon beams have the advantage of a markedly increased biological effectiveness characterized by enhanced ionization density in the individual tracks of the heavy particles, where DNA damage becomes clustered and therefore more difficult to repair, but is restricted to the end of their range. These superior biophysical and biological profiles of particle beams over conventional radiotherapy permit more precise dose localization and make them highly attractive for treating anatomically complex and radioresistant malignant tumors but without increasing the severe side effects in the normal tissue. More than half a century since Wilson proposed their use in cancer therapy, the effects of particle beams have been extensively investigated and the biological complexity of particle beam irradiation begins to unfold itself. The goal of this review is to provide an as comprehensive and up-to-date summary as possible of the different radiobiological aspects of particle beams for effective application in cancer treatment.     

SCANNING ELECTRON MICROSCOPY AND ELECTRON MICROPROBE ANALYSIS OF SILICIFICATION PATTERNS IN INFLORESCENCE BRACTS OF AVENA SATIVA

Using scanning electron microscopy, we determined the kinds and distribution of epidermal cell types in Avena inflorescence bracts (glume, lemma, and palea). Electron microprobe analysis of silica deposition in these epidermal cells showed that silica cells constitute one of the important deposition sites. Probe ratio data indicate that the silica deposited is 74 % pure. Significant amounts of silica also become deposited in the trichomes and lesser amounts in the walls of long epidermal cells. None could be detected in the stomata. The possible functional significance of silica deposition in epidermal cells of these bracts is discussed.     

Radiation-induced energy migration within solid DNA: the role of misonidazole as an electron trap

The "in-pulse" luminescence emission from solid DNA produced upon irradiation with electron pulses of energy below 260 keV has been investigated in vacuo at 293 K to gain an insight into the existence of radiation-induced charge/energy migration within DNA. The DNA samples contained misonidazole in the range 3 to 330 base pairs per misonidazole molecule. Under these conditions greater than 90% of the total energy is deposited in the DNA. The in-pulse radiation-induced luminescence spectrum of DNA was found to be critically dependent upon the misonidazole content of DNA. The luminescence intensity from the mixtures decreases with increasing content of misonidazole, and at the highest concentration, the intensity at 550 nm is reduced to 50% of that from DNA only. In the presence of 1 atm of oxygen, the observed emission intensity from DNA in the wavelength region 350-575 was reduced by 35-40% compared to that from DNA in vacuo. It is concluded that electron migration can occur in solid mixtures of DNA over a distance of up to about 100 base pairs.     

Response of rat skin to high-dose unidirectional x-ray microbeams: a histological study

There is growing interest in evaluating microbeam radiation therapy as a potential clinical modality. Microbeam radiation therapy uses arrays of parallel, microscopically thin (<100 microm) planes of synchrotron-generated X rays (microplanar beams, or microbeams). Due to the relatively low beam energies involved in microbeam radiation therapy (a median beam energy of 120 keV was used in the present study), the dose penetration of microbeams in tissue is lower than that used in conventional radiotherapy. This lower energy necessitates using a significantly elevated dose to the skin's surface during clinical microbeam therapy to ensure an adequate dose distribution in the target tumor. The findings of the present study, using a rat skin model, indicated that the skin had an extremely high tolerance to microbeam radiation at doses considerably in excess of those that were therapeutically effective in preclinical studies. A histological study was undertaken to evaluate the biological mechanisms underlying this high tolerance. The irradiation configuration employed single-exposure, unidirectional microbeams 90 microm wide, with 300 microm beam spacing on-center. The in-beam skin-surface absorbed doses were in the range 835-1335 Gy. Monte Carlo simulations of the dose distribution indicated that the "valley" dose, i.e. the radiation leakage between adjacent microbeams, was about 2.5% of the in-beam dose. The high tolerance of the rats' skin to microbeams and the rapid regeneration of the damaged segments of skin were attributed to the surviving clonogenic cells situated between the adjacent microplanar beams. In the epidermis, clonogenic cells in the hair follicular epithelium appeared to play a key role in the regeneration process.     

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.     

Investigation of viability of plant tissue in the environmental scanning electron microscopy

The advantages of environmental scanning electron microscopy (ESEM) make it a suitable technique for studying plant tissue in its native state. There have been few studies on the effects of ESEM environment and beam damage on the viability of plant tissue. A simple plant tissue, Allium cepa (onion) upper epidermal tissue was taken as the model for study. The change of moisture content of samples was studied at different relative humidities. Working with the electron beam on, viability tests were conducted for samples after exposure in the ESEM under different operating conditions to investigate the effect of electron beam dose on the viability of samples. The results suggested that without the electron beam, the ESEM chamber itself can prevent the loss of initial moisture if its relative humidity is maintained above 90%. With the electron beam on, the viability of Allium cepa (onion) cells depends both on the beam accelerating voltage and the electron dose/unit area hitting the sample. The dose can be controlled by several of the ESEM instrumental parameters. The detailed process of beam damage on cuticle-down and cuticle-up samples was investigated and compared. The results indicate that cuticular adhesion to the cell wall is relatively weak, but highly resistant to electron beam damage. Systematic study on the effect of ESEM operation parameters has been done. Results qualitatively support the intuitive expectations, but demonstrate quantitatively that Allium cepa epidermal cells are able to be kept in a hydrated and viable state under relevant operation condition inside ESEM, providing a basis for further in situ experiments on plant tissues.     

Hair follicle response to the variable l.e.t. of a helium ion beam

A homogeneous population of hair follicles in the rat tail has been used to analyse the in vivo response of a biological system to heavy particle irradiation. The conical configuration of the rat tail gives rise to a variable energy degradation of the beam thus yielding information on the damage elicited by the increasing l.e.t. of the helium beam at different sites on the same sample. By means of scanning electron microscopy three different zones were observed as direct evidence of helium ion penetration in the tail. Quantitative evaluation of radiation damage yielded results concerning hair follicle damage after increasing doses for different regions of the ionization curve.     

Disinfection of sewage sludge cake by an electron accelerator

Effects of radiation dose rate, electron energy and oxygen on disinfection of sewage sludge cake were studied to obtain technological information on disinfection by radiation. Sludge films were irradiated with electron beams at different voltages and various dose rates in oxygen-containing and oxygen-free atmospheres. Without oxygen, the surviving fraction of bacteria decreased with increasing irradiation dose, but depended little on the sludge film thickness. No effects of dose rate and energy change were found in the ranges from 20 kGy/h to 65 MGy/h and from 0.5 to 2.0 MeV when the film was thin enough to allow electron beam penetration. Similar results were obtained with γ-ray irradiation. In the oxygen-containing atmosphere, higher disinfection efficiency was obtained with thinner films and lower dose rates.     

Single photon radioluminescence. I. Theory and spectroscopic properties.

The excitation of a fluorescent molecule by a beta-decay electron (radioluminescence) depends upon the electron energy, the distance between radioactive 'donor' and fluorescent 'acceptor', and the excitation characteristics and solvent environment of the fluorophore. The theory for calculation of single photon radioluminescence (SPR) signals is developed here; in the accompanying paper, measurement methods and biological applications are presented. To calculate the three-dimensional spatial profile for electron energy deposition in an aqueous environment, a Monte Carlo calculation was performed incorporating theories of electron energy distributions, energy loss due to interactions with matter, and deflections in electron motion due to collisions. For low energy beta emitters, 50% of energy deposition occurs within 0.63 micron (3H, 18.5 keV), 22 microns (14C, 156 keV), 25 microns (35S, 167 keV), and 260 microns (36Cl, 712 keV) of the radioisotope. In close proximity to the beta emitter (100 nm, 3H; 10 microns, 14C) the probability for fluorophore excitation is approximately proportional to the inverse square of the distance between the beta emitter and fluorophore. To investigate the other factors that determine the probability for fluorophore excitation, SPR measurements were carried out in solutions containing 3H and a series of fluorophores in different solvents. In water, the probability of fluorescence excitation was nearly proportional to the integrated absorbance over a > 1,000-fold variation in absorbances. The probability of fluorescence excitation was enhanced up to 2,600-fold when the fluorophore was in a "scintillant" aromatic or hydrocarbon solvent. SPR emission spectra were similar to fluorescence emission spectra obtained with photon excitation. The single photon signal due to Bremsstrahlung increased with wavelength in agreement with theory. The distance dependence for the SPR signal predicted by the model was in good agreement with measurements in which a 14C donor was separated by known thicknesses of water from a fluorescently-coated coverglass. Quantitative predictions for radioluminescence signal as a function of donor-acceptor distance were developed for specific radioisotope-fluorophore geometries in biological samples.     

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.     

Interaction of an ion beam with the target in electron microscope applications

When based on the power-potential law of Lindhard et al. (Mat. Fys. Dan. Vid. Selsk, 33: 1–42, 1963) for ionic impact phenomena on the surfaces of a target, the universal curves of nuclear and electronic energy loss-energy, their resulting yield-energy relationships of sputtering and secondary electron emission yield-energy and range-energy have consistently been derived.According to the results obtained from the above experimental data, a diffusion model of an ion beam penetrating a target is proposed, which takes place throughout a hemisphere with its centre located at half the diffusion depth, and which is found to agree well with the empirical data of ion beam penetration, energy-dissipation profiles and the backscattering coefficient as a function of the reduced depth.Owing to the diffusion model's data, the total secondary electron emission yield due to both primary and backscattering ions is obtained. More importantly, radiation damage in ion beam applications is consistently evaluated as a function of the reduced energy ratio.     

Study of the hard component of pulsed X-ray emission of micropinch discharge plasma

A set of spectrometers that allow simultaneous measurements of the spectra of pulsed X-ray and electron emission from a micropinch discharge in a wide energy range (1.5?C500 keV) is described. The experimental results of the study of electron and X-ray spectra of micropinch discharge plasma are discussed. The mechanism for the formation of hard X-rays is caused by acceleration processes in micropinch discharge plasma.     

Silica deposition in relation to ageing of leaf tissues in Sasa veitchii (Carriere) Rehder (Poaceae: Bambusoideae)

BACKGROUND AND AIMS: Silica deposition is one of the important characteristics of plants in the family Poaceae. There have been many investigations into the distribution, deposition and physiological functions of silica in this family. Two hypotheses on silica deposition have been proposed based on these studies. First, that silica deposition occurs passively as a result of water uptake by plants, and second, that silica deposition is controlled positively by plants. To test these two apparently contradictory hypotheses, silica deposition in relation to the ageing of leaf tissues in Sasa veitchii was investigated. METHODS: Tissues were examined using a light microscope and a scanning electron microscope equipped with an energy dispersive X-ray microanalyser. KEY RESULTS: The deposition process differed depending on cell type. In mesophyll tissue, fusoid cells deposited large amounts of silica depending on leaf age after maturation, while chlorenchyma cells deposited little. In epidermal tissue, comprised of eight cell types, only silica cells deposited large amounts of silica during the leaf's developmental process and none after maturation. Bulliform cells, micro-hairs and prickle hairs deposited silica densely and continuously after leaf maturation. Cork cells, guard cells, long cells and subsidiary cells deposited silica at low levels. CONCLUSIONS: The significance of these observations is discussed in relation to the two hypotheses proposed for silica deposition in Poaceae. The results of the present study clearly indicate that both hypotheses are compatible with each other dependent on cell types.     

A semi-analytical model for calculating the penetration depth of a high energy electron beam in a water phantom with a magnetic field

PurposeAs an electron beam is incident on a uniform water phantom in the presence of a lateral magnetic field, the depth-dose distribution of the electron beam changes significantly and forms the well-known ‘Bragg peak’, with a depth-dose distribution similar to that of heavy ions. This phenomenon has pioneered a new field in the clinical application of electron beams. For such clinical applications, evaluating the penetration depth of electron beams quickly and accurately is the critical problem.MethodsThis paper describes a model for calculating the penetration depth of an electron beam rapidly and correctly in a water phantom under the influence of a magnetic field. The model was used to calculate the penetration depths under different conditions: the energies of electron beams of 6, 8, 12 and 15 MeV and the magnetic induction intensities of 0.75, 1.0, 1.5, 2.0 and 3.0 T. In addition, the calculation results were compared with the results of a Monte Carlo simulation.ResultsThe comparison results indicate that the difference between the two calculation methods was less than 0.5 cm. Moreover, the computing time of the calculation model was less than a second.ConclusionsThe semi-analytical model proposed in the present study enables the penetration depth of the electron beam in the presence of a magnetic field to be obtained with a computational efficiency higher than that of the Monte Carlo approach; thus, the proposed model has high potential for application.