Energy Deposition around Swift Carbon-Ion Tracks in Liquid Water.

Energetic carbon ions are promising projectiles used for cancer radiotherapy. A thorough knowledge of how the energy of these ions is deposited in biological media (mainly composed of liquid water) is required. This can be attained by means of detailed computer simulations, both macroscopically (relevant for appropriately delivering the dose) and at the nanoscale (important for determining the inflicted radiobiological damage). The energy lost per unit path length (i.e., the so-called stopping power) of carbon ions is here theoretically calculated within the dielectric formalism from the excitation spectrum of liquid water obtained from two complementary approaches (one relying on an optical-data model and the other exclusively on ab initio calculations). In addition, the energy carried at the nanometre scale by the generated secondary electrons around the ion's path is simulated by means of a detailed Monte Carlo code. For this purpose, we use the ion and electron cross sections calculated by means of state-of-the art approaches suited to take into account the condensed-phase nature of the liquid water target. As a result of these simulations, the radial dose around the ion's path is obtained, as well as the distributions of clustered events in nanometric volumes similar to the dimensions of DNA convolutions, contributing to the biological damage for carbon ions in a wide energy range, covering from the plateau to the maximum of the Bragg peak.

Electronic excitation spectra of cerium oxides: from ab initio dielectric response functions to Monte Carlo electron transport simulations.

Nanomaterials made of cerium oxides CeO2 and Ce2O3 have a broad range of applications, from catalysts in automotive, industrial or energy operations to promising materials to enhance hadrontherapy effectiveness in oncological treatments. To elucidate the physico-chemical mechanisms involved in these processes, it is of paramount importance to know the electronic excitation spectra of these oxides, which are obtained here through high-accuracy linear-response time-dependent density functional theory calculations. In particular, the macroscopic dielectric response functions  of both bulk CeO2 and Ce2O3 are derived, which compare remarkably well with the available experimental data. These results stress the importance of appropriately accounting for local field effects to model the dielectric function of metal oxides. Furthermore, we reckon the energy loss functions Im(-1/) of the materials, including the accurate evaluation of the momentum transfer dispersion from first-principles calculations. In this respect, by using Mermin-type parametrization we are able to model the contribution of different electronic excitations to the dielectric loss function. Finally, from the knowledge of the electron inelastic mean free path, together with the elastic mean free path provided by the relativistic Mott theory, we carry out statistical Monte Carlo (MC) electron transport simulations to reproduce the major features of the reported experimental reflection electron energy loss (REEL) spectra of cerium oxides. The good agreement with REEL experimental data strongly supports our approach based on MC modelling, whose main inputs were obtained using ab initio calculated electronic excitation spectra in a broad range of momentum and energy transfers.

Excitation and ionisation cross-sections in condensed-phase biomaterials by electrons down to very low energy: application to liquid water and genetic building blocks.

Electronic excitations and ionisations produced by electron impact are key processes in the radiation-induced damage mechanisms in materials of biological relevance, underlying important medical and technological applications, including radiotherapy, radiation protection in manned space missions and nanodevice fabrication techniques. However, experimentally measuring all the necessary electronic interaction cross-sections for every relevant material is an arduous task, so it is necessary having predictive models, sufficiently accurate yet easily implementable. In this work we present a model, based on the dielectric formalism, to provide reliable ionisation and excitation cross-sections for electron-impact on complex biomolecular media, considering their condensed-phase nature. We account for the indistinguishability and exchange between the primary beam and excited electrons, for the molecular electronic structure effects in the electron binding, as well as for low-energy corrections to the first Born approximation. The resulting approach yields total ionisation cross-sections, energy distributions of secondary electrons, and total electronic excitation cross-sections for condensed-phase biomaterials, once the electronic excitation spectrum is known, either from experiments or from a predictive model. The results of this methodology are compared with the available experimental data in water and DNA/RNA molecular building blocks, showing a very good agreement and a great predictive power in a wide range of electron incident energies, from the large values characteristic of electron beams down to excitation threshold. The proposed model constitutes a very useful procedure for computing the electronic interaction cross-sections for arbitrary biological materials in a wide range of electron incident energies.

Relative Role of Physical Mechanisms on Complex Biodamage Induced by Carbon Irradiation.

The effective use of swift ion beams in cancer treatment (known as hadrontherapy) as well as appropriate protection in manned space missions rely on the accurate understanding of the energy delivery to cells that damages their genetic information. The key ingredient characterizing the response of a medium to the perturbation induced by charged particles is its electronic excitation spectrum. By using linear-response time-dependent density functional theory, we obtained the energy and momentum transfer excitation spectrum (the energy-loss function, ELF) of liquid water (the main constituent of biological tissues), which was in excellent agreement with experimental data. The inelastic scattering cross sections obtained from this ELF, together with the elastic scattering cross sections derived by considering the condensed phase nature of the medium, were used to perform accurate Monte Carlo simulations of the energy deposited by swift carbon ions in liquid water and carried away by the generated secondary electrons, producing inelastic events such as ionization, excitation, and dissociative electron attachment (DEA). The latter are strongly correlated with cellular death, which is scored in sensitive volumes with the size of two DNA convolutions. The sizes of the clusters of damaging events for a wide range of carbon-ion energies, from those relevant to hadrontherapy up to those for cosmic radiation, predict with unprecedented statistical accuracy the nature and relative magnitude of the main inelastic processes contributing to radiation biodamage, confirming that ionization accounts for the vast majority of complex damage. DEA, typically regarded as a very relevant biodamage mechanism, surprisingly plays a minor role in carbon-ion induced clusters of harmful events.

Multiscale simulation of the focused electron beam induced deposition process.

Focused electron beam induced deposition (FEBID) is a powerful technique for 3D-printing of complex nanodevices. However, for resolutions below 10 nm, it struggles to control size, morphology and composition of the structures, due to a lack of molecular-level understanding of the underlying irradiation-driven chemistry (IDC). Computational modeling is a tool to comprehend and further optimize FEBID-related technologies. Here we utilize a novel multiscale methodology which couples Monte Carlo simulations for radiation transport with irradiation-driven molecular dynamics for simulating IDC with atomistic resolution. Through an in depth analysis of [Formula: see text] deposition on [Formula: see text] and its subsequent irradiation with electrons, we provide a comprehensive description of the FEBID process and its intrinsic operation. Our analysis reveals that simulations deliver unprecedented results in modeling the FEBID process, demonstrating an excellent agreement with available experimental data of the simulated nanomaterial composition, microstructure and growth rate as a function of the primary beam parameters. The generality of the methodology provides a powerful tool to study versatile problems where IDC and multiscale phenomena play an essential role.

Energy Spectra of Protons and Generated Secondary Electrons around the Bragg Peak in Materials of Interest in Proton Therapy.

The number and energy of secondary electrons generated around the trajectories of swift protons interacting with biological materials are highly relevant in proton therapy, due to the prominent role of low-energy electrons in the production of biodamage. For a given material, electron energy distributions are determined by the proton energy; and it is imperative that the distribution of proton energy at depths around the Bragg peak region be described as accurately as possible. With this objective, we simulated the energy distributions of proton beams of clinically relevant energies (50-300 MeV) at depths around the Bragg peak in liquid water and the water-equivalent polymer poly(methyl methacrylate) (PMMA). By using a simple model, this simulation has been conveniently extended to account for nuclear fragmentation reactions, providing depth-dose curves in excellent agreement with available experimental data. Special care has been taken to describe the electronic excitation spectrum of the target, taking into account its condensed phase nature. A predictive formula has been obtained for the mean value and the width of the proton energy distribution at the Bragg peak depth, quantities which are found to grow linearly with the initial energy of the beam, in good agreement with available data. To accurately characterize (in number and energy) the electrons generated around the proton paths, the energy distributions of the latter at each depth have been convoluted with the energy-dependent ionization inverse mean free paths. This results in a number of low-energy electrons around the Bragg peak larger than when only the proton beam average energy at the given depths is considered. The convoluted ionization inverse mean free path closely resembles the Bragg curve shape. The average energy of the secondary electrons is nearly constant (∼55 eV for liquid water and ∼43 eV for PMMA) in the plateau of the Bragg curve, independent of the proton incident energy and suddenly decaying once the Bragg peak is reached. These findings highlight the importance of a precise calculation of the proton beam energy distribution as a function of the target depth to reliably characterize the secondary electrons generated around the Bragg peak region.

Angular and energy distributions of electrons produced in arbitrary biomaterials by proton impact.

We present a simple method for obtaining reliable angular and energy distributions of electrons ejected from arbitrary condensed biomaterials by proton impact. Relying on a suitable description of the electronic excitation spectrum and a physically motivated relation between the ion and electron scattering angles, it yields cross sections in rather good agreement with experimental data in a broad range of ejection angles and energies, by only using as input the target composition and density. The versatility and simplicity of the method, which can be also extended to other charged particles, make it especially suited for obtaining ionization data for any complex biomaterial present in realistic cellular environments.

Energy deposition of H and He ion beams in hydroxyapatite films: a study with implications for ion-beam cancer therapy.

Ion-beam cancer therapy is a promising technique to treat deep-seated tumors; however, for an accurate treatment planning, the energy deposition by the ions must be well known both in soft and hard human tissues. Although the energy loss of ions in water and other organic and biological materials is fairly well known, scarce information is available for the hard tissues (i.e., bone), for which the current stopping power information relies on the application of simple additivity rules to atomic data. Especially, more knowledge is needed for the main constituent of human bone, calcium hydroxyapatite (HAp), which constitutes 58% of its mass composition. In this work the energy loss of H and He ion beams in HAp films has been obtained experimentally. The experiments have been performed using the Rutherford backscattering technique in an energy range of 450-2000 keV for H and 400-5000 keV for He ions. These measurements are used as a benchmark for theoretical calculations (stopping power and mean excitation energy) based on the dielectric formalism together with the MELF-GOS (Mermin energy loss function-generalized oscillator strength) method to describe the electronic excitation spectrum of HAp. The stopping power calculations are in good agreement with the experiments. Even though these experimental data are obtained for low projectile energies compared with the ones used in hadron therapy, they validate the mean excitation energy obtained theoretically, which is the fundamental quantity to accurately assess energy deposition and depth-dose curves of ion beams at clinically relevant high energies. The effect of the mean excitation energy choice on the depth-dose profile is discussed on the basis of detailed simulations. Finally, implications of the present work on the energy loss of charged particles in human cortical bone are remarked.

Water equivalent properties of materials commonly used in proton dosimetry.

The depth-dose distribution of proton beams in materials currently used in dosimetry measurements, such as liquid water, PMMA or graphite are calculated with the SEICS (Simulation of Energetic Ions and Clusters through Solids) code, where all the relevant effects in the evaluation of the energy deposited by the beam in the target are included, such as electronic energy-loss (including energy-loss straggling), multiple elastic scattering, electronic charge-exchange processes, and nuclear fragmentation interactions. Water equivalent properties are obtained for different proton beam energies and several targets of interest in dosimetry.

A study of the energy deposition profile of proton beams in materials of hadron therapeutic interest.

The energy delivered by a swift proton beam in materials of interest to hadron therapy (liquid water, polymethylmethacrylate or polystyrene) is investigated. An explicit condensed-state description of the target excitation spectrum based on the dielectric formalism is used to calculate the energy-loss rate of the beam in the irradiated materials. This magnitude is the main input in the simulation code SEICS (Simulation of Energetic Ions and Clusters through Solids) used to evaluate the dose as a function of the penetration depth and radial distance from the beam axis.

Inelastic cross sections for low-energy electrons in liquid water: exchange and correlation effects.

Low-energy electrons play a prominent role in radiation therapy and biology as they are the largest contributor to the absorbed dose. However, no tractable theory exists to describe the interaction of low-energy electrons with condensed media. This article presents a new approach to include exchange and correlation (XC) effects in inelastic electron scattering at low energies (below ∼10 keV) in the context of the dielectric theory. Specifically, an optical-data model of the dielectric response function of liquid water is developed that goes beyond the random phase approximation (RPA) by accounting for XC effects using the concept of the many-body local-field correction (LFC). It is shown that the experimental energy-loss-function of liquid water can be reproduced by including into the RPA dispersion relations XC effects (up to second order) calculated in the time-dependent local-density approximation with the addition of phonon-induced broadening in N. D. Mermin's relaxation-time approximation. Additional XC effects related to the incident and/or struck electrons are included by means of the vertex correction calculated by a modified Hubbard formula for the exchange-only LFC. Within the first Born approximation, the present XC corrections cause a significantly larger reduction (∼10-50%) to the inelastic cross section compared to the commonly used Mott and Ochkur approximations, while also yielding much better agreement with the recent experimental data for amorphous ice. The current work offers a manageable, yet rigorous, approach for including non-Born effects in the calculation of inelastic cross sections for low-energy electrons in liquid water, which due to its generality, can be easily extended to other condensed media.

Semiempirical model for the ion impact ionization of complex biological media.

We present a semiempirical model for calculating the electron emission from any organic compound after ion impact. With only the input of the density and composition of the target we are able to evaluate its ionization cross sections using plausible approximations. Results for protons impacting in the most representative biological targets (such as water or DNA components) show a very good comparison with experimental data. Because of its simplicity and great predictive effectiveness, the method can be immediately extended to any combination of biological target and charged particle of interest in ion beam cancer therapy.

A combined molecular dynamics and Monte Carlo simulation of the spatial distribution of energy deposition by proton beams in liquid water.

We have evaluated the spatial distribution of energy deposition by proton beams in liquid water using the simulation code SEICS (Simulation of Energetic Ions and Clusters through Solids), which combines molecular dynamics and Monte Carlo techniques and includes the main interaction phenomena between the projectile and the target constituents: (i) the electronic stopping force due to energy loss to target electronic excitations, including fluctuations due to the energy-loss straggling, (ii) the elastic scattering with the target nuclei, with their corresponding energy loss and (iii) the dynamical changes in projectile charge state due to electronic capture and loss processes. An important feature of SEICS is the accurate account of the excitation spectrum of liquid water, based on a consistent solid-state description of its energy-loss-function over the whole energy and momentum space. We analyse how the above-mentioned interactions affect the depth distribution of the energy delivered in liquid water by proton beams with incident energies of the order of several MeV. Our simulations show that the position of the Bragg peak is determined mainly by the stopping power, whereas its width can be attributed to the energy-loss straggling. Multiple elastic scattering processes contribute slightly only at the distal part of the Bragg peak. The charge state of the projectiles only changes when approaching the end of their trajectories, i.e. near the Bragg peak. We have also simulated the proton-beam energy distribution at several depths in the liquid water target, and found that it is determined mainly by the fluctuation in the energy loss of the projectile, evaluated through the energy-loss straggling. We conclude that a proper description of the target excitation spectrum as well as the inclusion of the energy-loss straggling is essential in the calculation of the proton beam depth-dose distribution.

Energy loss of hydrogen- and helium-ion beams in DNA: calculations based on a realistic energy-loss function of the target.

We have calculated the electronic energy loss of proton and α-particle beams in dry DNA using the dielectric formalism. The electronic response of DNA is described by the MELF-GOS model, in which the outer electron excitations of the target are accounted for by a linear combination of Mermin-type energy-loss functions that accurately matches the available experimental data for DNA obtained from optical measurements, whereas the inner-shell electron excitations are modeled by the generalized oscillator strengths of the constituent atoms. Using this procedure we have calculated the stopping power and the energy-loss straggling of DNA for hydrogen- and helium-ion beams at incident energies ranging from 10 keV/nucleon to 10 MeV/nucleon. The mean excitation energy of dry DNA is found to be I  =  81.5 eV. Our present results are compared with available calculations for liquid water showing noticeable differences between these important biological materials. We have also evaluated the electron excitation probability of DNA as a function of the transferred energy by the swift projectile as well as the average energy of the target electronic excitations as a function of the projectile energy. Our results show that projectiles with energy ≲100 keV/nucleon (i.e., around the stopping-power maximum) are more suitable for producing low-energy secondary electrons in DNA, which could be very effective for the biological damage of malignant cells.