Properties Of Ion Beams Research Articles

Progress in heavy ion cancer therapy at IMP and future development

AbstractBasic research on heavy ion cancer therapy such as radiobiology, medical physics, and therapeutic technique has been conducted at the Institute of Modern Physics (IMP), Chinese Academy of Sciences since 1995. Based on the achievements acquired in the basic research and the requirements for a heavy ion accelerator for radiotherapy purposes, a dedicated heavy ion therapy facility named Heavy Ion Medical Machine (HIMM) was designed at IMP and constructed in Wuwei, China. The HIMM facility consists of two electron cyclotron resonance ion sources, one cyclotron as the injector and one synchrotron as the main accelerator, and four different treatment rooms equipped with passive or active beam delivery systems, and accelerates carbon ions up to 400 MeV/u. After the performance inspection of HIMM organized by the National Medical Device Inspection Center, preclinical tests like cell and animal radiobiological experiments and dosimetric verification using anthropomorphic phantoms for elucidating the biophysical properties of the carbon ion beams provided by HIMM were carried out. According to the Chinese medical device regulations, a clinical trial in which 46 tumor patients were recruited and two hospitals participated was conducted in the HIMM facility, aiming at evaluating the treatment safety and short‐term efficacy of the medical device. The success of the clinical trial helped the HIMM facility be authorized by the Chinese government as a class III medical device. In this paper, all the aspects mentioned above are introduced and discussed, and implications for future improvements are also given.

Enhancing Tissue Equivalence in 7Li Heavy Ion Therapy with MC Algorithm Optimized Polymer-Based Bioinks.

The unique physical properties of heavy ion beams, particularly their distinctive depth-dose distribution and sharp lateral dose reduction profiles, have led to their widespread adoption in tumor therapy worldwide. However, the physical properties of heavy ion beams must be investigated to deliver a sufficient dose to tumors without damaging organs at risk. These studies should be performed on phantoms made of biomaterials that closely mimic human tissue. Polymers can serve as soft tissue substitutes and are suitable materials for building radiological phantoms due to their physical, mechanical, biological, and chemical properties. Extensive research, development, and applications of polymeric biomaterials have been encouraged due to these properties. In this study, we investigated the ionization, recoils, phonon release, collision events, and lateral straggle properties of polymeric biomaterials that closely resemble soft tissue using lithium-ion beams and Monte Carlo Transport of Ions in Matter simulation. The results indicated that the Bragg peak position closest to soft tissue was achieved with a 7.3% difference in polymethylmethacrylate, with an average recoils value of 10.5%. Additionally, average values of 33% were observed in collision events and 22.6% in lateral straggle. A significant contribution of this study to the existing literature lies in the exploration of secondary interactions alongside the assessment of linear energy transfer induced by the 7Li beam used for treatment. Furthermore, we analyzed the tissue-equivalent properties of polymer biomaterials using heavy ion beams, taking into account phonon release resulting from ionization, recoils, lateral straggle, and all other interactions. This approach allows for the evaluation of the most suitable polymeric biomaterials for heavy ion therapy while considering the full range of interactions involved.

Polarimetry for 3He Ion Beams from Laser–Plasma Interactions

We present a compact polarimeter for 3He ions with special emphasis on the analysis of short-pulsed beams accelerated during laser–plasma interactions. We discuss the specific boundary conditions for the polarimeter, such as the properties of laser-driven ion beams, the selection of the polarization-sensitive reaction in the polarimeter, the representation of the analyzing-power contour map, the choice of the detector material used for particle identification, as well as the production procedure of the required deuterated foil-targets. The assembled polarimeter has been tested using a tandem accelerator delivering unpolarized 3He ion beams, demonstrating good performance in the few-MeV range. The statistical accuracy and the deduced figure-of-merit of the polarimetry are discussed, including the count-rate requirement and the lower limit of accuracy for beam-polarization measurements at a laser-based ion source.

Ultra-intense laser-accelerated ion beams for high-gain inertial fusion: the effect of the ion mass on the beam properties

This paper presents the results of detailed numerical studies of the properties of ion beams generated by a laser from targets with various atomic numbers under conditions relevant for ion fast ignition (IFI) of inertial fusion. The interaction of a 200 kJ 1 ps infrared (1.05 μm) laser with Li, C, Al, Ti, Cu and CH2 flat targets with the same areal mass density was numerically simulated using an advanced 2D3V particle-in-cell code. For each target, a set of ion beam characteristics important for IFI was determined. A detailed quantitative comparison of the IFI-relevant parameters of Li, C, Al, Ti and Cu ion beams and the proton beam (from the CH2 target) was made. The laser-accelerated Cu ion beam was found to achieve significantly higher values of beam intensity, fluence and ‘useful’ energy (for IFI), having a smaller angular divergence and a narrower energy spectrum than the beam of light ions or protons. Thus, it is shown for the first time that laser-accelerated heavy ion beams can achieve IFI-relevant parameters higher than light ion or proton beams and can potentially meet IFI requirements.

Laser-driven acceleration of ion beams for high-gain inertial confinement fusion

Inertial confinement fusion (ICF) is currently one of the two main paths towards an energy source based on thermonuclear fusion. A promising ICF option is ion fast ignition (IFI), in which the ignition of nuclear fuel is initiated by an intense laser-driven ion beam. This paper presents the results of systematic numerical (particle-in-cell) studies of the properties of laser-driven carbon ion beams produced under conditions relevant for IFI, and the feasibility of achieving beam parameters required for fuel ignition is discussed. It was found that a 1 ps 200 kJ infrared laser driver is capable of producing ion beams with parameters required for IFI, even with a simple non-optimised target, but only at small distances (⩽0.1 mm) from the target. At such distances, the beam intensity and fluence exceeds 5 × 1021 W cm−2 and 2 GJ cm−2, respectively, while the beam energy approaches 30 kJ. The ion beam parameters can be significantly improved by carefully selecting the target thickness and shape. However, even with an optimised target, achieving the beam parameters required for IFI is possible only at distances from the target below 0.5 mm. The ion acceleration is accompanied by the emission of powerful (⩾50 PW) pulses of short-wavelength synchrotron radiation which are the source of significant ion energy losses and may pose a threat to the fusion infrastructure. In addition to ICF, the extremely intense ion beams demonstrated in the paper can be a unique research tool for research in nuclear physics, high energy-density physics or materials science.

Characterizing Radiation Effectiveness in Ion-Beam Therapy Part II: Microdosimetric Detectors

The specific advantages of ion beams for application in tumor therapy are attributed to their different macroscopic and microscopic energy deposition pattern as compared to conventional photon radiation. On the macroscopic scale, the dose profile with a Bragg peak at the highest depths and small lateral scattering allow a better conformation of the dose to the tumor. On the microscopic scale, the localized energy deposition around the trajectory of the particles leads to an enhanced biological effectiveness, typically expressed in terms of clinically significant relative biological effectiveness (RBE). Experimental investigations reveal complex dependencies of RBE on many physical and biological parameters, as e.g. ion species, dose, position in the field, and cell or tissue type. In order to complement the experimental work, different approaches are used for the characterization of the specific physical and biological properties of ion beams. In a set of two papers, which are linked by activities within a European HORIZON 2020 project about nuclear science and application (ENSAR2), we describe recent developments in two fields playing a key role in characterizing the increased biological effectiveness. These comprise the biophysical modelling of RBE and the microdosimetric measurements in complex radiation fields. This second paper focuses on microdosimeters and on the importance of providing the instrumental measurement of the spectra of the imparted energy. The relevance of microdosimetric quantities, complementary to the absorbed dose is emphasized. This parts provides an overview of the microdosimetric concepts and the recent experimental developments in the field of microdosimetry applied to ion beam therapy. Finally, a non-exhaustive, dedicated section in included to emphasize the relevance of Monte Carlo simulations as tool for the design of the microdosimetric detectors and for the interpretation of the experimental results. For the two distinctive clinical beams of protons and carbon ions, the lineal-energy parameters are correlated to the clinical concept of Linear Energy Transfer (LET) and RBE. The possibilities of applying experimental microdosimetry in ion-beam therapy are discussed considering the consolidated irradiation characteristics as well as the most recent developments.

Characterizing Radiation Effectiveness in Ion Beam Therapy Part I: Introduction and Biophysical Modeling of RBE Using the LEMIV

The specific advantages of ion beams for application in tumor therapy are attributed to their different macroscopic and microscopic energy deposition pattern as compared to conventional photon radiation. On the macroscopic scale, the inverted dose profile with a Bragg peak and small lateral scattering allow a better conformation of the dose to the tumor. On the microscopic scale, the localized energy deposition around the trajectory of the particles leads to an enhanced biological effectiveness, typically expressed in terms of the relative biological effectiveness (RBE). Experimental investigations reveal complex dependencies of RBE on many physical and biological parameters, as e.g. ion species, dose, position in the field and cell or tissue type. In order to complement the experimental work, different approaches are used for the characterization of the specific physical and biological properties of ion beams. In a set of two papers, which are linked by activities within a European HORIZON 2020 project about nuclear science and application (ENSAR2), we describe recent developments in two fields playing a key role in characterizing the increased biological effectiveness. These comprise the biophysical modelling of RBE and the microdosimetric measurements in complex radiation fields. This first paper gives a brief introduction into these fields and then focuses on aspects of biophysical modelling of RBE, specifically on semi-empirical approaches that are currently used in treatment planning for ion beam therapy. It summarizes the status and recent developments of the Local Effect Model (LEM) and its conceptual framework and shows examples of model validation using recent experimental data. The model is compared to other approaches, e.g. to the Microdosimetric-Kinetic Model (MKM), that builds the bridge to the experimental microdosimetric work.

Properties of heavy ion beams produced by a PW sub-picosecond laser

The paper reports the results of numerical studies on the generation of heavy ions from a sub-micrometre gold target irradiated by a high-energy (60 J) high-intensity (∼ 2 × 1020 W/cm2) sub-ps laser pulse. The properties of the heavy ion beam produced from a 0.5-μm gold target with and without hydrogen contaminants are investigated using a multi-dimensional (2D3 V) particle-in-cell code. It was found that in the case of the pure (without the contaminants) target, the ion beam contains over 20 ion species with a charge state > 30 and a total number of high-energy (> 20 MeV) ions reaching values well above 1012. The ion energy spectrum is broad, with maximum energies > 1 GeV and mean energies > 100 MeV . At a distance ∼ 1 mm from the target, the intensity of the ion beam is ∼ 1015 W/cm2, the ion fluence reaches ∼ 1016 ions/cm2, and the ion pulse duration is ∼ 100 ps. The contaminants significantly reduce the ion beam parameters and both the mean ion energy and the intensity and fluence of the ion beam generated from the contaminated gold target are almost an order of magnitude lower than those produced from the pure target. Heavy ion beams with the parameters obtained in the case of the pure gold target are barely achievable in conventional RF-driven accelerators, so they can open the door to new areas of research, in particular in high energy-density physics.

Acceleration of carbon ion beams by an ultraviolet laser under conditions relevant for ion fast ignition of inertial fusion

The properties of carbon ion beams produced by a 100-kJ, 1-ps, KrF ultraviolet laser under conditions relevant for ion fast ignition (IFI) of DT fusion are numerically investigated using the 2D3V particle-in-cell code, and the possibility of achieving the ion beam parameters required for IFI is tested. The numerical simulations of carbon ion acceleration were carried out for flat carbon targets of various thicknesses (LT) and for various laser beam apertures (dL) on the target, while the laser pulse duration and energy were fixed. It was found that both the radiation pressure acceleration (RPA) mechanism and the sheath acceleration mechanism significantly affects the characteristics of the ion beam, with the RPA dominating in the case of thicker targets (LT ∼ 10–30 μm). The ion beam parameters depend to a significant extent on the target thickness and the distance from the target. The mean and maximum ion energy decrease with the increase of LT from 3 μm to 30 μm, while the ion beam intensity, the beam energy fluence and the total energy of the “useful part” of the ion beam (with an aperture ⩽ 50 μm) reach maximum values at LT ∼ 5–10 μm. For the optimal value of LT and a small distance x from the target (x ∼ LT), the ion beam parameters are close to or higher than what is required for IFI. However, due to the angular divergence of the ion beam, the beam intensity and fluence decrease with an increase in the distance from the target, and at x ⩾ 0.5 mm the beam parameters are below the values required for fusion ignition. To reach these values, higher laser energies and/or more sophisticated schemes of ion acceleration are required.

State-of-the-Art and Future Prospects of Ion Beam Therapy: Physical and Radiobiological Aspects

The number of facilities offering radiotherapy with protons or heavier ions is continuously increasing; worldwide, more than 160 000 patients have been treated with protons, and more than 25 000 with heavier ions. Despite this substantial clinical experience, there is still a need for further developments and improvements which are specific to the properties of particle beams. This contribution briefly summarizes the main physical and radiobiological properties of ion beams which make them favorable for application in tumor therapy. In addition, major challenges that are currently addressed in different research areas are reviewed. These comprise the fields of biophysical modeling, treatment planning, mitigation of target motion and novel approaches based on particular spatio-temporal beam delivery techniques.

Acceleration of carbon ions to high energies by a multi-PW laser

Extreme Light Infrastructure (ELI) is a large-scale European project, still in the development stage, offering parameters of laser drivers required for multiple applications (femtosecond pulse duration, ultra-relativistic laser intensities ∼ 1022 - 1023 W/cm2), however studies of ion acceleration in the given intensity regime are still in the very early stages and require a deeper understanding of the processes occurring during laser-matter interactions to maximize the efficiency of ion acceleration. The purpose of this work is a numerical examination of the properties of carbon ion beams produced during the interaction of an ultra-intense laser beams (of intensities ∼ 1021 – 1023 W/cm2 and pulse duration order of femtoseconds, predicted to be available at ELI-NP, Romania) with C12 target. The dependence of ion beam parameters, such as intensity, energy spectrum, maximum and average ion energy and spatial distribution of ion charge density, on laser pulse parameters (mainly intensity) and the target thickness is investigated. The possibility of generation of high intensity, GeV energy ion beams in the foregoing conditions is demonstrated. The obtained results can be useful for research in high energy-density physics, nuclear physics or medical applications of ion beams.

I207] Ion-based imaging and in-vivo range verification in ion beam therapy: Status and perspectives

Swift ions in matter exhibit favorable physical and biological properties, particularly owing to the ability of concentrating their energy deposition at a well-localized depth at their end of range, so-called Bragg peak. Compared to conventional external beam radiotherapy modalities, ion beams thus promise superior tumour-dose conformality and optimal sparing of surrounding critical organs and healthy tissue, with expected benefits for deep-seated, inoperable tumour sites as well as pediatric patients. Hence, interest in this emerging technology has rapidly increased worldwide in the last decade(s). To date, about 70 ion therapy facilities (of which ∼20 in Europe) are operational, predominantly with proton beams, and about the same amount is under construction or planning. Despite considerable recent technological advances, particularly regarding ion accelerators and scanning beam delivery systems, along with integration of in-room volumetric X-ray imaging, full clinical exploitation of the favorable ballistic properties of ion beams is still hampered by the yet unsolved problem of range uncertainties, preventing an exact localization of the Bragg peak (hence dose maximum) in tissue. Although these uncertainties can be mitigated by the introduction of cautious safety margins and careful choice of beam directions, new approaches are being extensively investigated to tackle this issue at the stage of treatment planning or treatment delivery. Here, emphasis will be given to unconventional imaging modalities exploiting energetic ion beams for refined assessment of the tissue stopping properties pre-treatment, as well as to online/post-treatment detection of acoustic and nuclear-based emissions induced by ion interaction in tissue for in vivo verification of the beam range. This contribution will critically review the main ongoing developments and initial pre-clinical or clinical experience, discussing the prospects of unconventional imaging modalities for eventually harnessing the ballistic selectivity of ion beam therapy in the clinical practice.

Enhancement of Intact Ion Yields in ToF-SIMS Using Molecular Cluster Ion Beams

Recently, water and some other molecules are applied to the massive cluster projectiles for SIMS to improve the secondary ion yields by chemical effects. The ionization probability should be influenced by the properties of the primary ion beams as well as the chemical nature of the sample surface. However, the mechanisms of ionization by the large cluster collision is still unclear. In this study, we have generated water, methanol and methane molecular cluster ion beams and investigated the secondary ion emission from amino acid thin films bombarded by the molecular cluster ion projectiles.

Ionoacoustics: A new direct method for range verification

The superior ballistic properties of ion beams may offer improved tumor-dose conformality and unprecedented sparing of organs at risk in comparison to other radiation modalities in external radiotherapy. However, these advantages come at the expense of increased sensitivity to uncertainties in the actual treatment delivery, resulting from inaccuracies of patient positioning, physiological motion and uncertainties in the knowledge of the ion range in living tissue. In particular, the dosimetric selectivity of ion beams depends on the longitudinal location of the Bragg peak, making in vivo knowledge of the actual beam range the greatest challenge to full clinical exploitation of ion therapy. Nowadays, in vivo range verification techniques, which are already, or close to, being investigated in the clinical practice, rely on the detection of the secondary annihilation photons or prompt gammas, resulting from nuclear interaction of the primary ion beam with the irradiated tissue. Despite the initial promising results, these methods utilize a not straightforward correlation between nuclear and electromagnetic processes, and typically require massive and costly instrumentation. On the contrary, the long-term known, yet only recently revisited process of "ionoacoustics", which is generated by local tissue heating especially at the Bragg peak, may offer a more direct approach to in vivo range verification, as reviewed here.

Clinical implementation and range evaluation of in vivo PET dosimetry for particle irradiation in patients with primary glioma

PurposeThe physical and biological properties of ion-beams offer various advantages in comparison to conventional radiotherapy, though uncertainties concerning quality assurance are still left. Due to the inverted depth dose profile, range accuracy is of paramount importance.We investigated the range deviations between planning simulation and post-fractional PET/CT measurement from particle therapy in primary glioblastoma. Methods and materials20 patients with glioblastoma undergoing particle therapy at our institution were selected. 10 received a proton-boost, 10 a carbon-ion-boost in addition to standard treatment. After two fractions, we performed a PET/CT-scan of the brain. We compared the resulting range deviation based on the Most-likely-shift method between the two measurements, and the measurements with corresponding expectations, calculated with the Monte-Carlo code FLUKA. ResultsA patient’s two measurements deviated by 0.7mm (±0.7mm). Overall comparison between measurements and simulation resulted in a mean range deviation of 3.3mm (±2.2mm) with significant lower deviations in the 12C-arm. ConclusionThe used planning concepts display the actual dose distributions adequately. The carbon ion group’s results are below the used PTV safety margins (3mm). Further adjustments to the simulation are required for proton irradiations. Some anatomical situations require particular attention to ensure highest accuracy and safety.

Variance-based sensitivity analysis of biological uncertainties in carbon ion therapy

PurposeBiological models to estimate the relative biological effectiveness (RBE) or the equivalent dose in 2 Gy fractions (EQD2) are needed for treatment planning and plan evaluation in carbon ion therapy. We present a model-independent, Monte Carlo based sensitivity analysis (SA) approach to quantify the impact of different uncertainties on the biological models. Methods and materialsThe Monte Carlo based SA is used for the evaluation of variations in biological parameters. The key property of this SA is the high number of simulation runs, each with randomized input parameters, allowing for a statistical variance-based ranking of the input variations. The potential of this SA is shown in a simplified one-dimensional treatment plan optimization. Physical properties of carbon ion beams (e.g. fragmentation) are simulated using the Monte Carlo code FLUKA. To estimate biological effects of ion beams compared to X-rays, we use the Local Effect Model (LEM) in the framework of the linear-quadratic (LQ) model. Currently, only uncertainties in the output of the biological models are taken into account. Results/conclusionsThe presented SA is suitable for evaluation of the impact of variations in biological parameters. Major advantages are the possibility to access and display the sensitivity of the evaluated quantity on several parameter variations at the same time. Main challenges for later use in three-dimensional treatment plan evaluation are computational time and memory usage. The presented SA can be performed with any analytical or numerical function and hence be applied to any biological model used in carbon ion therapy.

Heavy ion radiography and tomography

In the latest years, radiation therapy with ion beams has been rapidly spreading worldwide. This is mainly due to the favourable interaction properties of ion beams with matter, offering the possibility of more conformal dose deposition with superior sparing of healthy tissue in comparison to conventional photon radiation. Moreover, heavier ions like carbon offer a selective increase of biological effectiveness which can be advantageous for the treatment of tumours being resistant to sparsely ionizing radiation. However, full clinical exploitation of the advantages offered by ion beams is still challenged by the lack of exact knowledge of the beam range within the patient. Therefore, increasing research efforts are being devoted to the goal of reducing range uncertainties in ion beam therapy. In this context, ion transmission imaging is being recognized as a promising modality capable of providing valuable pre- (or even “in-between”) treatment information on the patient-specific stopping properties for indirect in-vivo range verification and low dose image guidance at the treatment site. The more recent availability of energetic ion beam sources at therapeutic treatment facilities, in combination with the advances in detector technologies and computational power, have considerably renewed the interest in this imaging technique. Nowadays, many research efforts are being devoted to the development of novel detector prototypes for heavy ion radiography and tomography, as will be reviewed in this contribution.

Properties of Ion Beams Generated by Nitrogen Plasma Focus

Numerical experiments have been systematically carried out using the modified Lee model code on various plasma focus devices operated with nitrogen gas. The ion beam properties (ion beam energy, ion beam flux, ion beam fluence, beam ion number, ion beam current, power flow density, and damage factor) of the plasma focus have been studied versus gas pressure for each plasma focus device. The results show that, for these studied plasma focus devices, the mean ion energies decrease with increasing gas pressure, while the beam ion number increases with higher pressure. The fluence, flux, ion current, power flow density and damage factor have maximum values at the optimum pressure. It is shown that, the maximum power flow densities range from 1012 to 1014 W m−2 and the damage factor values reach almost 109–1011 W m−2 s0.5. The obtained results provide much needed benchmark reference values and scaling trends for ion beams of a plasma focus operated in nitrogen gas. These results could be used as an indicator for ion properties emitted from nitrogen plasma focus for various applications including material processing.

PET Reconstruction From Truncated Projections Using Total-Variation Regularization for Hadron Therapy Monitoring

Hadron therapy exploits the properties of ion beams to treat tumors by maximizing the dose released to the target and sparing healthy tissue. With hadron beams, the dose distribution shows a relatively low entrance dose which rises sharply at the end of the range, providing the characteristic Bragg peak that drops quickly thereafter. It is of critical importance in order not to damage surrounding healthy tissues and/or avoid targeting underdosage to know where the delivered dose profile ends-the location of the Bragg peak. During hadron therapy, short-lived β+-emitters are produced along the beam path, their distribution being correlated with the delivered dose. Following positron annihilation, two photons are emitted, which can be detected using a positron emission tomography (PET) scanner. The low yield of emitters, their short half-life, and the wash out from the target region make the use of PET, even only a few minutes after hadron irradiation, a challenging application. In-beam PET represents a potential candidate to estimate the distribution of β+-emitters during or immediately after irradiation, at the cost of truncation effects and degraded image quality due to the partial rings required of the PET scanner. Time-of-flight (ToF) information can potentially be used to compensate for truncation effects and to enhance image contrast. However, the highly demanding timing performance required in ToF-PET makes this option costly. Alternatively, the use of maximum-a-posteriori- expectation-maximization (MAP-EM), including total variation (TV) in the cost function, produces images with low noise, while preserving spatial resolution. In this paper, we compare data reconstructed with maximum-likelihood-expectation-maximization (ML-EM) and MAP-EM using TV as prior, and the impact of including ToF information, from data acquired with a complete and a partial-ring PET scanner, of simulated hadron beams interacting with a polymethyl methacrylate (PMMA) target. The results show that MAP-EM, in the absence of ToF information, produces lower noise images and more similar data compared to the simulated β+ distributions than ML-EM with ToF information in the order of 200-600 ps. The investigation is extended to the combination of MAP-EM and ToF information to study the limit of performance using both approaches.

Ion beam properties after mass filtering with a linear radiofrequency quadrupole

The properties of ion beams passing through a linear radiofrequency quadrupole mass filter were investigated with special attention to their dependence on the mass resolving power. Experimentally, an increase of the transverse emittance was observed as the mass-to-charge selectivity of the mass filter was raised. The experimental behavior was confirmed by beam transport simulations.