Heavy Charged Particle Irradiation Research Articles

High turnover and rescue effect of XRCC1 in response to heavy charged particle radiation

The DNA damage response is a highly orchestrated process. The involvement of the DNA damage response factors in DNA damage response depends on their biochemical reactions with each other and with chromatin. Using online live-cell imaging combined with heavy ion microbeam irradiation, we studied the response of the scaffold protein X-ray repair cross-complementary protein 1 (XRCC1) at the localized DNA damage in charged particle irradiated HT1080 cells expressing XRCC1-tagged RFP. The results showed that XRCC1 was recruited to the DNA damage with ultrafast kinetics in a poly ADP-ribose polymerase-dependent manner. The consecutive reaction model well explained the response of XRCC1 at ion hits, and we found that the XRCC1 recruitment was faster and dissociation was slower in the G2 phase than those in the G1 phase. The fractionated irradiation of the same cells resulted in accelerated dissociation at the previous damage sites, and the dissociated XRCC1 immediately recycled with a higher recruitment efficiency. Our data revealed XRCC1’s new rescue mechanism and its high turnover in DNA damage response, which benefits our understanding of the biochemical mechanism in DNA damage response.

RELATIVE HCP THERMOLUMINESCENCE AND OPTICAL ABSORPTION EFFICIENCIES: THE DEMISE OF TRACK STRUCTURE THEORY.

The thermoluminescence relative efficiency, ηTST, of LiF:Mg,Ti and LiF:Mg,Cu,P following heavy charged particle irradiation is calculated using track structure theory and compared with experimental measurements. The calculations use both 60Co generated values of secondary electron dose response and values of the dose response at lower photon energies. In both materials there is poor agreement with experiment. Optical absorption relative efficiencies are also in disagreement. For the F band, ηexpt'l/ηTST=2.0 and 2.6 for He ions and protons, respectively. The values of ηexpt'l/ηTST for the 4.0-eV band, resulted in 0.18 (protons) and <0.12 (He ions). An indication that the 4.0-eV trapping structure is either destroyed or de-populated during the heavy charged particle (HCP) slowing down. The large deviations of ηexpt'l/ηHCP from unity demonstrate that TST, which predicts HCP induced radiation effects from the exclusive action of the released secondary electrons, is woefully inadequate.

The malignant transformation of osteoid osteoma in the cervical spine to high-grade osteosarcoma: a case report and review of literature

Purpose Osteoid osteoma occasionally occur in the spine, but their malignant transformation is not common. We present an extremely rare case of the malignant transformation of an osteoid osteoma to high-grade osteosarcoma that formed in the pedicle and spread to the lateral mass of the cervical spine. Case presentation We report the case of an 18-year-old man who suffered from neck pain as an initial symptom. The size of the radiolucent lesion was 12 mm in diameter at the time of diagnosis. Intralesional tumour resection and autologous bone grafting were performed. The remaining tumour grew gradually for 40 months after the surgery; therefore, the tumour had grown rapidly till 51 months after the initial diagnosis. At this stage, the tumour size was approximately 6-fold larger than the initial size, and resulted in progressive paraplegia. A biopsy revealed that the tumour had transformed into a high-grade osteosarcoma. Heavy charged particle irradiation was performed to control tumour growth. Conclusions There is a possibility of malignant transformation of osteoid osteoma. Patients with osteoid osteoma or osteoblastoma should be carefully observed, especially for recurrent tumours after an intralesional resection.

TL/OSL response of carbon ion beam irradiated NaMgF3:Tb

Fluoroperovskites are an important class of thermoluminescence (TL)/optically stimulated luminescence (OSL) materials known for their high sensitivity and other good characteristics particularly when doped with a suitable impurity. Fluoroperovskites have not yet been explored for heavy charged particle irradiation like carbon which is commonly used for cancer treatment. In the current work, TL and OSL properties of 85 MeV carbon ion beam irradiated NaMgF3:Tb samples have been investigated in detail at different fluences. Undoped and Tb3+ (0.5 mol%) doped NaMgF3 samples have been synthesized by the melting method. The formation of the material is confirmed using the XRD technique. The crystallite size of undoped and Tb3+ doped NaMgF3 samples are estimated to be 100 nm and 89 nm respectively. TL studies reveal that undoped NaMgF3 shows a well-isolated TL glow peak centered at 412 K while Tb3+ doped NaMgF3 shows more intense TL glow peak at 416 K with a small shoulder peak at 481 K along with a new peak at 647 K. Further, TL glow curves have been analyzed for 85 MeV carbon ion irradiated samples of NaMgF3 for low fluences (1 × 105–1 × 107 ions/cm2) and high fluences (2 × 109–5 × 1012 ions/cm2) to study the dose-response. CW-OSL decay curves of 85 MeV carbon ion irradiated undoped and Tb3+ doped NaMgF3 samples show high OSL intensity under blue light stimulation. The OSL dose-response has been recorded at high (1 × 108–1 × 1010 ions/cm2) and low (1 × 105–1 × 107 ions/cm2) fluences. Linear TL and OSL behaviour in the range 1 × 105–5 × 106 ions/cm2 has been observed. Also, other properties like batch homogeneity and fading studies have been carried out. The related TL/OSL kinetic parameters were determined. Analysis of TL/OSL properties of NaMgF3:Tb suggests that it exhibits appropriate properties for carbon ion beam dosimetry for its utilization in medical applications.

Alpha particle irradiation of bulk and exfoliated MoS2 and WS2 membranes

The properties of two-dimensional transition metal dichalcogenide (TMDC) nanosheets have been intensively studied in recent years as these compounds have emerged as promising materials for future electronic, photonic and sensor applications. Some of these applications may require the nanosheets to be exposed to radiation fields; therefore, an understanding of their interaction mechanisms with ionising radiation is required.In our experiment, we administer 1.66 MeV helium nuclei to bulk and liquid phase exfoliated MoS2 and WS2 membranes to two total absorbed doses. Raman spectroscopy shows small changes, within the spectrometer resolution, in all samples. Although small, some reproducible changes are observed such as a blueshift of the E2g1 and A1g modes in the bulk MoS2 membrane irradiated to a high total absorbed dose; these shifts are accompanied by a small broadening of both peaks. In bulk WS2 membranes, He2+ irradiation induces a blueshift and monotonic mean peak width decrease of the 2LA(M) phonon mode with increasing fluence. The structural changes associated to these peak shifts are currently unknown. Raman spectroscopy, in agreement with energy dispersive x-ray spectroscopy, shows that amorphous carbon is present in the exfoliated MoS2 and WS2 membranes after irradiation. It is suggested that this amorphous carbon could be formed by radiolytic amorphisation of residual solvent, retained within the ripplocations of the exfoliated nanosheets.Due to the morphology of the liquid phase exfoliated nanosheets, they exhibit greater radiation stability than bulk TMDCs when exposed to heavy charged particle radiation. These results differ from those previously reported for monolayer and bulk MoS2 produced by mechanical exfoliation. The relative radiation stability of the liquid phase exfoliated nanosheets is expected to arise from attenuation and dissipation of the ion beam energy by the residual solvent and the amorphous carbon subsequently produced.

Modulation of graphene field effect by heavy charged particle irradiation

Device architectures based on the two-dimensional material graphene can be used for sensing of electromagnetic and particle radiation. The sensing mechanism may be direct, by absorbance of radiation by the graphene or the immediately adjacent material, and indirect, via the field effect principle, whereby the change in conductivity within a semiconducting absorber substrate induces electric field change at graphene. Here, we report on a graphene field effect transistor (GFET) sensitive to heavy charged particle radiation (α particles) at MeV energies by use of the indirect sensing mechanism. Both the continuous and discrete changes of graphene are observed, and the latter are attributed to single α particle interactions with the GFET. While this study provides the basis for understanding of the irradiation effects, it also opens prospects for the use of GFETs as heavy charged particle detectors.

The more important heavy charged particle radiotherapy of the future is more likely to be with heavy ions rather than protons

The more important heavy charged particle radiotherapy of the future is more likely to be with heavy ions rather than protons

MO‐E‐500‐01: Point and Counter Point Debate: The More Important Heavy Charged Particle Radiotherapy of the Future Is More Likely to Be with Heavy Ions Rather Than Protons

Over the past decade there has been considerable interest and progress in the use of heavy ions such as protons and carbon in an attempt to improve the effectiveness of radiotherapy. Both have a physical advantage over photons because of their Bragg peaks, but only heavier ions such as carbon have a potential biological advantage. This has led to the claim that the most important heavy charged particle radiotherapy of the future is more likely to be with heavy ions rather than protons, and this is the premise argued in this debate.Arguments FOR the Proposition include:• relative to protons, heavier ions exhibit reduced lateral scattering, reduced range straggling, and increased dose to the tumor compared to the entrance dose• accurate positioning of the Bragg peak can be verified by in vivo measurements with heavier ions but not with protons• with heavier ions there is increased RBE in the tumor compared to normal tissues• with heavier ions there is increased effectiveness in hypoxic tumorsArguments AGAINST the Proposition include:• proton facilities cost 2–3 times less than those for heavier ions• cost and size of isocentric gantries for protons are much less• there are large uncertainties in the RBE in the heavier ion Bragg peak• with protons, there is the potential for reoxygenation during a course of therapy• due to fragmentation, heavier ion beams exhibit a tail of high‐LET radiation beyond the Bragg peakArguing for the Proposition is Oliver Jakel, Ph.D. Dr. Jakel completed his Ph.D. in Theoretical Physics at the University Erlangen, Germany in 1994. He then moved to the Department for Medical Physics, German Cancer Research Center (DKFZ), Heidelberg, where he is currently Full Professor and Director of the Heidelberg Ion Beam Therapy Facility of the University Hospital. Arguing against the Proposition is Alfred R. Smith, Ph.D. Dr. Smith obtained his Ph.D. in Physics from Texas Tech University, Lubbock, TX, in 1970. After completing a Postdoctoral Fellowship in Medical Physics at The University of Texas, M. D. Anderson Hospital and Tumor Institute, he held faculty positions at several institutions until he moved back to M. D. Anderson in 2002 as a Full Professor and Director of Proton Therapy Development, a position he held until 2010.Learning Objectives:1. To understand why heavy ions might be more suitable than photons for the treatment of some cancers2. To understand the relative benefits of therapy with heavier ions compared with protons3. To understand the relative benefits of therapy with protons compared with heavier ions

Conduction band/valence band kinetic modeling of the LiF:Mg,Ti system incorporating creation of defects in the irradiation stage

A conduction band/valence band kinetic model is described for the irradiation stage of the thermoluminescent LiF:Mg,Ti system. Unlike previous investigations the model incorporates creation of fluorine vacancies via irradiation and their subsequent partial filling by electrons in the relaxation stage leading to the creation of F centers. The radiation induced vacancies thus operate as additional competitors to the 4eV electron trapping center (TC) associated with composite glow peak 5 in the glow curve of LiF:Mg,Ti. With the appropriate choice of parameter-values the model successfully predicts the experimentally measured, linear/exponentially saturating dose response of the optical absorption (OA) bands of the 4eV TC and the 5.45eV competitive center (CC) which serves as well as the recombination stage competitor. The increased competition due to the creation of negative ion vacancies during irradiation is found to lead to changes in the population dose response characteristics of the various centers taking part in the TL mechanism. The implication of these changes on the relative thermoluminescence (TL) efficiency following heavy charged particle (HCP) irradiation is discussed.

Modeling of beam customization devices in the pencil-beam splitting algorithm for heavy charged particle radiotherapy

A broad-beam-delivery system for radiotherapy with protons or ions often employs multiple collimators and a range-compensating filter, which offer complex and potentially useful beam customization. It is however difficult for conventional pencil-beam algorithms to deal with fine structures of these devices due to beam-size growth during transport. This study aims to avoid the difficulty with a novel computational model. The pencil beams are initially defined at the range-compensating filter with angular-acceptance correction for upstream collimation followed by stopping and scattering. They are individually transported with possible splitting near the aperture edge of a downstream collimator to form a sharp field edge. The dose distribution for a carbon-ion beam was calculated and compared with existing experimental data. The penumbra sizes of various collimator edges agreed between them to a submillimeter level. This beam-customization model will be used in the greater framework of the pencil-beam splitting algorithm for accurate and efficient patient dose calculation.

鼻腔・副鼻腔に発生した未分化神経外胚葉性腫瘍例

A 66-year-old woman referred for right cheek swelling was found to have a soft mass filling the right nasal cavity. Computed tomography and magnetic resonance imaging showed a huge right maxillary sinus tumor with bone destruction. Biopsy showed the tumor to consist of small round atypical cells immunohistochemically positive for cytokeratin, EMA, synaptophysin, and CD99, but negative for desmin and chromogranin. The diagnosis was primitive neuroectodermal tumor. Chemotherapy followed by heavy charged particle radiotherapy shrank the tumor dramatically. She died of multiple lymph node, lung, liver, and bone metastasis.

Dose calculation algorithm of fast fine-heterogeneity correction for heavy charged particle radiotherapy

This work addresses computing techniques for dose calculations in treatment planning with proton and ion beams, based on an efficient kernel-convolution method referred to as grid-dose spreading (GDS) and accurate heterogeneity-correction method referred to as Gaussian beam splitting. The original GDS algorithm suffered from distortion of dose distribution for beams tilted with respect to the dose-grid axes. Use of intermediate grids normal to the beam field has solved the beam-tilting distortion. Interplay of arrangement between beams and grids was found as another intrinsic source of artifact. Inclusion of rectangular-kernel convolution in beam transport, to share the beam contribution among the nearest grids in a regulatory manner, has solved the interplay problem. This algorithmic framework was applied to a tilted proton pencil beam and a broad carbon-ion beam. In these cases, while the elementary pencil beams individually split into several tens, the calculation time increased only by several times with the GDS algorithm. The GDS and beam-splitting methods will complementarily enable accurate and efficient dose calculations for radiotherapy with protons and ions.

COTS Silicon diodes as radiation detectors in proton and heavy charged particle radiotherapy 1

Modern radiotherapy facilities for cancer treatment such as the Heavy Ion Therapy Center (HIT) in Heidelberg, Germany, allow for sub-millimeter precision in dose deposition. For measurement of such dose distributions and characterization of the particle beams, detectors with high spatial resolution are necessary. Here, a detector based on the commercially available COTS photodiode (BPW-34) is presented. When applied in hadronic beams of protons and carbon ions, the detector reproduces dose distribution well, but its response decreases rapidly by radiation damage. However, for MeV photon beams, the detector exhibits a similar behavior as found in diode detectors usually applied in radiotherapy.

MO‐SAM‐BRB‐01: Biological Aspects of Heavy Charged Particle Radiation Therapy

The relative biological effectiveness (RBE) is defined as the ratio of the doses required by two radiations to cause the same level of effect. Thus, the RBE depends on the dose and the biological endpoint.Proton therapy has been based on the use of a generic RBE of 1.1, which is applied to all treatments independent of dose/fraction, position in the irradiated volume, initial beam energy or the particular tissue. The variability of RBE in clinical situations is believed to be within 10% but quantitative dependencies of the RBE on various physical and biological properties are disregarded. The magnitude of RBE values and their variations is significantly larger for Carbon ion therapy. Studies have demonstrated significant RBE values of more than 3 in clinically relevant scenarios for Carbon ions. Further, there might be considerable variations in RBE within the irradiated volume that are being considered in treatment planning and delivery.Heavy ions have a potential advantage compared to protons when it comes to their therapeutic ratio due to an elevated RBE in the tumor (based on the oxygen enhancement ratio and higher average LET values) compared to the surrounding tissue. However, on the other hand, at present there are still considerable uncertainties in heavy ion RBE values. Elevated RBE values (even for protons) might be expected particularly near the edges of the high‐dose volume because doses may be deposited by high‐LET particles. The increase in RBE as a function of depth in the patient results in an extension of the bio‐effective range of the beam. Further, because RBE values may increase with deceasing dose causing elevated RBE values for organs at risk compared to the target area. In order to incorporate detailed RBE modeling in treatment planning as a function of LET, dose and endpoint, two aspects have to be considered. Firstly, the available information from experimental studies and secondly, our ability to calculate RBE values for a given treatment plan based on parameters extracted from such experiments. RBE values are often based on cell survival data because this is the main endpoint of interest in radiation therapy. However, one migt expect differences in RBE for cell survival compared to cell mutation, the latter being an important endpoint for late effects.This educational session will focus on summarizing the mechanisms behind RBE variations among treatment modalities. Further, RBE variations as a function of LET, tissue and dose will be presented based on experimental and simulated data for proton and Carbon ion beams. Finally, different approaches for theoretical modeling of RBE values for treatment planning purposes will be discussed briefly.Learning Objectives:1. Understand the mechanisms behind heavy charged particle RBE values2. Understand the variations of RBE as a function of physical and biological parameters3. Understand the clinical implication of RBE values in proton and Carbon ion therapy

Heavy-Ion Microbeams—Development and Applications in Biological Studies

High-linear-energy-transfer (LET) heavy charged particle radiation has been used in radiotherapy and radiation breeding because of its greater biological effectiveness compared with low-LET radiation. The health risk assessment for astronauts due to space radiation during interplanetary manned missions is also an important issue concerning the biological effects of heavy-ion radiation. Localized irradiation of specific regions within organisms using heavy-ion microbeam systems provides an attractive means of investigating the mechanism of heavy-ion radiation action. In addition, heavy-ion microbeams can be used as a radio-microsurgical tool for analyzing a broad range of biological phenomena. This paper reviews briefly the current status concerning the development of heavy-ion microbeams for use on living organisms with particular emphasis on its applications in biological studies in eukaryotes including plants, silkworm, nematode, and cultured plant and mammalian cells. Heavy-ion-induced bystander effects and its LET dependency will also be addressed.

The grid-dose-spreading algorithm for dose distribution calculation in heavy charged particle radiotherapy

A new variant of the pencil-beam (PB) algorithm for dose distribution calculation for radiotherapy with protons and heavier ions, the grid-dose spreading (GDS) algorithm, is proposed. The GDS algorithm is intrinsically faster than conventional PB algorithms due to approximations in convolution integral, where physical calculations are decoupled from simple grid-to-grid energy transfer. It was effortlessly implemented to a carbon-ion radiotherapy treatment planning system to enable realistic beam blurring in the field, which was absent with the broad-beam (BB) algorithm. For a typical prostate treatment, the slowing factor of the GDS algorithm relative to the BB algorithm was 1.4, which is a great improvement over the conventional PB algorithms with a typical slowing factor of several tens. The GDS algorithm is mathematically equivalent to the PB algorithm for horizontal and vertical coplanar beams commonly used in carbon-ion radiotherapy while dose deformation within the size of the pristine spread occurs for angled beams, which was within 3 mm for a single 150-MeV proton pencil beam of 30 degrees incidence, and needs to be assessed against the clinical requirements and tolerances in practical situations.

LET dependence of thermoluminescent efficiency and peak height ratio of CaF 2:Tm

First-order thermoluminescence (TL) kinetics computerized glow curve deconvolution (CGCD) and manual analysis of the composite peak structures have been applied to study the behaviour of glow peaks 3 and 5 in CaF 2:Tm (TLD-300, Harshaw-Thermo Fisher Scientific) single crystals after heavy charged particle (HCP) irradiation with respect to Co 60 gamma rays for a linear energy transfer (LET) interval from 2.3 to 339.4 keV μ m - 1 . The ratio of peak 5 to peak 3 heights can be used to evaluate effective LET and correct measured doses for TL efficiency. The applicability of this idea to dose equivalent estimation in exotic radiation fields of complex composition is discussed critically.

Effects of Interfractional Changes on Range in Heavy Charged Particle Radiotherapy of Lung Cancer

Intrafractional and interfractional anatomical changes impact the accuracy of delivered dose in radiotherapy, particularly in charged particle radiotherapy. Intrafractional sources of anatomical change arise from cardiac and respiratory motion. Interfractional anatomical changes are a result of tumor size and shape variations, tissue density changes and tissue thickness variations. We have performed a quantitative analysis of range variations due to interfractional anatomical changes in charged particle therapy over the treatment course.

Microdosimetry, track structure and the response of thermoluminescence detectors

Several properties of the response of thermoluminescence detectors after doses of ionising radiation can be explained by analysing the structure of charged particle tracks. Information on the topology of interaction points around the path of a charged particle can be represented through the radial distribution of average dose around the particle's path (Track Structure) or through quantities such as lineal energy, y , or specific energy, z , applied in Microdosimetry. A principal assumption in all microdosimetric and track structure models is that, on a per average dose basis, the local efficiency of the TL processes taking place in any small volume located in the non-uniformly distributed dose distribution around the particle's path is similar to that after irradiation with a uniformly distributed dose of γ -rays. Since saturation of γ -ray response at high doses then translates to saturation of this response over regions of high dose close to the path of the heavy charged particle, track structure theory and microdosimetric models are able to explain the decrease of TL efficiency after irradiation by heavy charged particles, and the anomalously low photon energy response of LiF:Mg,Cu,P after doses of X-rays. The enhanced photon energy response and enhanced response after heavy charged particle irradiation of LiF:Mg,Ti are connected with the supralinearity of this detector at higher doses of gamma-rays: if this response is sublinear (prior to saturation) the measured photon energy response is lower, and if it is supralinear—it is higher than that expected from the calculation of the interaction cross sections alone. The explanation of the correlation between dose-, energy- and LET-responses of TLDs is perhaps the most important contribution of microdosimetry to solid state dosimetry.

Nonmonotonic dose dependence of OSL intensity due to competition during irradiation and readout

The nonmonotonic dose dependence of thermoluminescence has been observed in several materials; a recent publication (Lawless, J.L., Chen, R., Lo, D., Pagonis, V., 2005. A model for non-monotonic dose dependence of thermoluminescence (TL). J. Phys. Condens. Matter 17, 737–753.) gave a theoretical account based on competition between trapping states or recombination centers during the excitation and/or readout stages. A similar effect has been observed in the optically stimulated luminescence (OSL) of some materials such as quartz and Al 2O 3:C (e.g., Yukihara, E.G., Whitley, V.H., McKeever, S.W.S., Akselrod, A.E., Akselrod, M.S., 2004a. Effect of high-dose irradiation on the optically stimulated luminescence of Al 2O 3:C. Radiat. Meas. 38, 317–330; Yukihara, E.G., Gaza, R., McKeever, S.W.S., Soares, C.G., 2004b. Optically stimulated luminescence and thermoluminescence efficiencies for high-energy heavy charged particle irradiation in Al 2O 3:C. Radiat. Meas. 38, 59–70.). The model of competition has now been developed to explain the nonmonotonic dose dependence of OSL. A distinction is made between two cases. In one, the competition during excitation causes the filling of the relevant radiative center to be nonmonotonic with the dose, and as a result, the OSL intensity behaves in a similar way. This can take place with a “minimal” model including one trapping state and two kinds of recombination centers, one radiative and the other nonradiative. In the other case, all the relevant concentrations increase monotonically with the dose, and the nonmonotonic dose dependence of the OSL signal is mainly due to competition in the readout stage. In this case, it appears that the requirement for nonmonotonic dose dependence is a system with two trapping states and two kinds of recombination centers.