Track-average Linear Energy Transfer Research Articles

Towards precise LET measurements based on energy deposition of therapeutic ions in Timepix3 detectors

Objective. There is an increasing interest in calculating and measuring linear energy transfer (LET) spectra in particle therapy in order to assess their impact in biological terms. As such, the accuracy of the particle fluence energy spectra becomes paramount. This study focuses on quantifying energy depositions of distinct proton, helium, carbon, and oxygen ion beams using a silicon pixel detector developed at CERN to determine LET spectra in silicon. Approach. While detection systems have been investigated in this pursuit, the scarcity of detectors capable of providing per-ion data with high spatial and temporal resolution remains an issue. This gap is where silicon pixel detector technology steps in, enabling online tracking of single-ion energy deposition. The used detector consisted of a 300 µm thick silicon sensor operated in partial depletion. Main results. During post-processing, artifacts in the acquired signals were identified and methods for their corrections were developed. Subsequently, a correlation between measured and Monte Carlo-based simulated energy deposition distributions was performed, relying on a two-step recalibration approach based on linear and saturating exponential models. Despite the observed saturation effects, deviations were confined below 7% across the entire investigated range of track-averaged LET values in silicon from 0.77 keV µm−1 to 93.16 keV µm−1. Significance. Simulated and measured mean energy depositions were found to be aligned within 7%, after applying artifact corrections. This extends the range of accessible LET spectra in silicon to clinically relevant values and validates the accuracy and reliability of the measurements. These findings pave the way towards LET-based dosimetry through an approach to translate these measurements to LET spectra in water. This will be addressed in a future study, extending functionality of treatment planning systems into clinical routine, with the potential of providing ion-beam therapy of utmost precision to cancer patients.

Technical note: Determination of proton linear energy transfer from the integral depth dose.

Proton linear energy transfer (LET) is associated with the relative biological effectiveness of radiation on tissues. Monte Carlo (MC) simulations have been known to be the preferred method to calculate LET. Detectors have also been built to measure LET, but they need to be calibrated with MC simulations. To propose and test a MC-free method for determining LET from the measured integral depth dose (LFI) of the protons of interest. LFI consists of three steps: (1) IDD measurements, (2) extraction of energy spectrum (ES) from the IDD, and (3) LET determination from the extracted ES and the stopping power of each energy. To validate the accuracy of the extraction of ES, we use Gaussian ES to synthesize IDD, extract ES from the synthesized IDD, and then compare the original (ground truth) and extracted ES. LETs calculated from the original and extracted ES are also compared. To obtain the LET of protons of interest, we measure IDDs by a large-area plane-parallel ionization chamber in water. Finally, TOPAS MC is employed to simulate IDDs, ES, and LETs. From the simulated IDD, the extracted ES and LET are compared with the simulations from TOPAS MC. From the synthesized IDDs, the LETs agreed excellently when the peak energies ≥10 and 1.25 MeV with depth resolutions 0.1and 0.01mm, respectively. For energy<1.25 MeV, even higher depth resolution than 0.01mm is required. From the MC simulated IDDs, our track-averaged LET excellently agreed with MC simulation, but not the LETd. Our LETd was smaller than MC simulated LETd in the shallow region but larger in the distal Bragg peak region. LET can be accurately determined from the IDD. This method can be used in the clinic to commission or validate LETs from other measurement methods or a treatment planning system.

On the perturbation effect and LET dependence of beam quality correction factors in carbon ion beams.

In a recent study, we reported beam quality correction factors, fQ , in carbon ion beams using Monte Carlo (MC) methods for a cylindrical and a parallel-plate ionization chamber (IC). A non-negligible perturbation effect was observed; however, the magnitude of the perturbation correction due to the specific IC subcomponents was not included. Furthermore, the stopping power data presented in the International Commission on Radiation Units and Measurements (ICRU) report 73 were used, whereas the latest stopping power data have been reported in the ICRU report 90. The aim of this study was to extend our previous work by computing fQ correction factors using the ICRU 90 stopping power data and by reporting IC-specific perturbation correction factors. Possible energy or linear energy transfer (LET) dependence of the fQ correction factor was investigated by simulating both pristine beams and spread-out Bragg peaks (SOBPs). The TOol for PArticle Simulation (TOPAS)/GEANT4 MC code was used in this study. A 30 × 30 × 50 cm3 water phantom was simulated with a uniform 10 × 10 cm2 parallel beam incident on the surface. A Farmer-type cylindrical IC (Exradin A12) and two parallel-plate ICs (Exradin P11 and A11) were simulated in TOPAS using the manufacturer-provided geometrical drawings. The fQ correction factor was calculated in pristine carbon ion beams in the 150-450 MeV/u energy range at 2 cm depth and in the middle of the flat region of four SOBPs. The kQ correction factor was calculated by simulating the fQo correction factor in a 60 Co beam at 5 cm depth. The perturbation correction factors due to the presence of the individual IC subcomponents, such as the displacement effect in the air cavity, collecting electrode, chamber wall, and chamber stem, were calculated at 2 cm depth for monoenergetic beams only. Additionally, the mean dose-averaged and track-averaged LET was calculated at the depths at which the fQ was calculated. The ICRU 90 fQ correction factors were reported. The pdis correction factor was found to be significant for the cylindrical IC with magnitudes up to 1.70%. The individual perturbation corrections for the parallel-plate ICs were <1.0% except for the A11 pcel correction at the lowest energy. The fQ correction for the P11 IC exhibited an energy dependence of >1.00% and displayed differences up to 0.87% between pristine beams and SOBPs. Conversely, the fQ for A11 and A12 displayed a minimal energy dependence of <0.50%. The energy dependence was found to manifest in the LET dependence for the P11 IC. A statistically significant LET dependence was found only for the P11 IC in pristine beams only with a magnitude of <1.10%. The perturbation and kQ correction factor should be calculated for the specific IC to be used in carbon ion beam reference dosimetry as a function of beam quality.

4He dose- and track-averaged linear energy transfer: Monte Carlo algorithms and experimental verification

Objective. In the present hadrontherapy scenario, there is a growing interest in exploring the capabilities of different ion species other than protons and carbons. The possibility of using different ions paves the way for new radiotherapy approaches, such as the multi-ions treatment, where radiation could vary according to target volume, shape, depth and histologic characteristics of the tumor. For these reasons, in this paper, the study and understanding of biological-relevant quantities was extended for the case of 4He ion. Approach. Geant4 Monte Carlo based algorithms for dose- and track-averaged LET (Linear Energy Transfer) calculations, were validated for 4He ions and for the case of a mixed field characterised by the presence of secondary ions from both target and projectile fragmentation. The simulated dose and track averaged LETs were compared with the corresponding dose and frequency mean values of the lineal energy, and , derived from experimental microdosimetric spectra. Two microdosimetric experimental campaigns were carried out at the Italian eye proton therapy facility of the Laboratori Nazionali del Sud of Istituto Nazionale di Fisica Nucleare (INFN-LNS, Catania, I) using two different microdosimeters: the MicroPlus probe and the nano-TEPC (Tissue Equivalent Proportional Counter). Main results. A good agreement of and with and experimentally measured with both microdosimetric detectors MicroPlus and nano-TEPC in two configurations: full energy and modulated 4He ion beam, was found. Significance. The results of this study certify the use of a very effective tool for the precise calculation of LET, given by a Monte Carlo approach which has the advantage of allowing detailed simulation and tracking of nuclear interactions, even in complex clinical scenarios.

Changes of the linear energy transfer (LET) and beam width of therapeutic carbon ion beam in density heterogeneous phantoms

This work aims to investigate the changes in the linear energy transfer (LET) spectra distribution and the beam spot width of a therapeutic carbon ion beam in density heterogeneous phantoms. Three different heterogeneous phantoms were fabricated using a combination of solid water, lung, and bone tissue slabs and irradiated by a single energy carbon beam (276.5 MeV u−1). CR-39 detectors were used for experimental measurements and the Monte Carlo toolkit Geant4 was employed for theoretical simulations. The results demonstrated that the measured LET spectra agree well with the simulation results. The lung and bone tissues displayed no obvious effect on the spectral distribution of LET. The dose-average LET was invariant and showed no obvious difference in the different materials, while the track-average LET increased in the lung and decreased in the bone materials. Similarly, the beam spot size increased in the lung, and decreased in the bone materials. Additionally, the fluence of the secondary fragments varied in different tissues. These findings are expected to provide cross-validation data for the quality assurance of carbon ion therapy and to be beneficial for validating the base data in treatment planning systems.

Multi-centric analysis of linear energy transfer distribution from clinical proton beam based on TOPAS

Linear energy transfer (LET), a key parameter of relative biological effectiveness (RBE) in proton therapy, is not easy to measure or simulate in a standardized protocol. A multi-centric analysis of dose-averaged LET (LETd) and track-averaged LET (LETt) including individual particle contributions, scoring slab thickness, inhomogeneous medium and clinical beam configurations are investigated using the Monte Carlo code TOPAS. Primary and secondary protons are scored separately within the simulation. It is found that the primary protons are the major contribution to LET at the dose plateau and Bragg Peak (BP) regions, whilst the secondary protons have complete contribution to the tail-LET beyond the BP. The calculated LETt is always lower than LETd, nearly a factor of two lower in the region distal to the BP. Varying the scoring slab thickness shows a negligible influence on LETt, whereas, there is up to 26% discrepancy in LETd at 5-cm depth with thicknesses varying from 0.1 mm to 2 mm for 153.3 MeV proton beam. Moreover, smaller scoring thickness of 0.1 mm results in large fluctuations for tail LETd. LETd distributions with 3-cm thick bone- and lung-slab at the entrance of water phantom against primary and secondary protons' contribution are derived. A small trough appears at the position of inserted inhomogeneous material and large spikes which could account for the changes of cross section in nuclear interactions by secondary protons display on the tail of LETd curve. Regarding the modulated beams, substantial-high LET values are obtained at both-sides along the beam path which should gain more attention when calculating LET in clinical applications. In conclusion, the selection of Monte Carlo simulation schemes indeed affects the calculated LET values, more procedures should be considered when building bridges between LET and radiological effectiveness.

A Monte Carlo study of different LET definitions and calculation parameters for proton beam therapy

The strong in vitro evidence that proton Relative Biological Effectiveness (RBE) varies with Linear Energy Transfer (LET) has led to an interest in applying LET within treatment planning. However, there is a lack of consensus on LET definition, Monte Carlo (MC) parameters or clinical methodology. This work aims to investigate how common variations of LET definition may affect potential clinical applications. MC simulations (GATE/GEANT4) were used to calculate absorbed dose and different types of LET for a simple Spread Out Bragg Peak (SOBP) and for four clinical PBT plans covering a range of tumour sites. Variations in the following LET calculation methods were considered: (i) averaging (dose-averaged LET (LETd) & track-averaged LET); (ii) scoring (LETd to water, to medium and to mass density); (iii) particle inclusion (LETd to all protons, to primary protons and to particles); (iv) MC settings (hit type and Maximum Step Size (MSS)). LET distributions were compared using: qualitative comparison, LET Volume Histograms (LVHs), single value criteria (maximum and mean values) and optimised LET-weighted dose models. Substantial differences were found between LET values in averaging, scoring and particle type. These differences depended on the methodology, but for one patient a difference of ∼100% was observed between the maximum LETd for all particles and maximum LETd for all protons within the brainstem in the high isodose region (4 keV μm−1 and 8 keV μm−1 respectively). An RBE model using LETd including heavier ions was found to predict substantially different LET-weighted dose compared to those using other LET definitions. In conclusion, the selection of LET definition may affect the results of clinical metrics considered in treatment planning and the results of an RBE model. The authors’ advocate for the scoring of dose-averaged LET to water for primary and secondary protons using a random hit type and automated MSS.

Dose-average linear energy transfer of electrons released in liquid water and LiF:Mg,Ti by low-energy x-rays, 137Cs and 60Co gamma

For many years, track-average linear energy transfer (LET), has been used to quantify the radiation-induced phenomena in biological and physical systems. However, due to the need for including into the radiotherapy treatment planning system, parameters that are clinical and biologically relevant, a precise knowledge of the dose-average LET, becomes essential. Besides, several dosimetric studies have revealed that is fundamental to describe the dosimeter’s response induced by photons. The most important data sets publicly available for of electron generated by photons are those reported for measurements performed in methane-based tissue-equivalent gas. However, comparing to liquid water, the electron spectra generated by low photon energy might not be similar due to the photoelectric effect. Thus, this work aimed at investigating the of electron spectra generated in liquid water and LiF:Mg,Ti by ten x-ray beams from 20 kV to 300 kV, 137Cs and 60Co gamma. The results suggest that is more sensitive to the surrounding environment than and consequently, it might be a more appropriate parameter to quantify the radiation effect and damage in matter induced by photons. Besides, good agreement (6% to 12% differences versus 10% to 15% uncertainties in the experiments) was observed between the data obtained in this work for liquid water and the experimental values published for methane-based tissue-equivalent gas at energies above 60 keV. Whereas at lowest energies, the minimum difference is around 18% which can be associated to the difference between the two media.

MONTE CARLO SIMULATIONS OF SPATIAL LET DISTRIBUTIONS IN CLINICAL PROTON BEAMS.

The linear energy transfer (LET) is commonly used as a parameter which describes the quality of the radiation applied in radiation therapy with fast ions. In particular in proton therapy, most models which predict the radiobiological properties of the applied beam, are fitted to the dose-averaged LET, LETd. The related parameter called the fluence- or track-averaged LET, LETt, is less frequently used. Both LETt and in particular LETd depends profoundly on the encountered secondary particle spectrum. For proton beams including all secondary particles, LETd may reach more than 3 keV/um in the entry channel of the proton field. However, typically the charged particle spectrum is only averaged over the primary and secondary protons, which is in the order of 0.5 keV/um for the same region. This is equal to assuming that the secondary particle spectrum from heavier ions is irrelevant for the resulting radiobiology, which is an assertion in the need of closer investigation. Models which rely on LETd should also be clear on what type of LETd is used, which is not always the case. Within this work, we have extended the Monte Carlo particle transport code SHIELD-HIT12A to provide dose- and track-average LET-maps for ion radiation therapy treatment plans.

Validating α-particle emission from 211At-labeled antibodies in single cells for cancer radioimmunotherapy using CR-39 plastic nuclear track detectors.

Recently, 211At has received increasing attention as a potential radionuclide for cancer radioimmunotherapy. It is a α-particle emitter, which is extremely effective against malignant cells. We demonstrate a method to verify the efficiency of 211At-labeled trastuzumab antibodies (211At-trastuzumab) against HER2 antigens, which has not been determined for radioimmunotherapy. A CR-39 plastic nuclear detector is used for measuring the position and the linear energy transfer (LET) of individual 211At α- particle tracks. The tracks and 211At-trastuzumab-binding cells were co-visualized by using the geometric information recorded on the CR-39. HER2-positive human gastric cancer cells (NCI-N87), labelled with 211At-trastuzumab, were dropped on the centre of the CR-39 plate. Microscope images of the cells and the corresponding α-tracks acquired by position matching were obtained. In addition, 3.5 cm × 3.5 cm macroscopic images of the whole plate were acquired. The distribution of number of α-particles emitted from single cells suggests that 80% of the 211At-trastuzumab-binding cells emitted α-particles. It also indicates that the α-particles may strike the cells several times along their path. The track-averaged LET of the α-particles is evaluated to be 131 keV/μm. These results will enable quantitative evaluation of delivered doses to target cells, and will be useful for the in vitro assessment of 211At-based radioimmunotherapeutic agents.

Track-average LET of secondary electrons generated in LiF:Mg,Ti and liquid water by 20–300 kV x-ray, 137Cs and 60Co beams

Electrons generated in matter by photons could be a fundamental basis for an adequate analysis of radiation effects and damage. We have studied separately the ‘primary electrons’ generated directly by photons from the ‘secondary electrons’ (SE) produced by electron–electron interactions. In this work, track-average linear energy transfer, , of SE in LiF:Mg,Ti and liquid water produced by twelve photon energy beams from 20 kV x-ray to 60Co gamma rays have been investigated using the EGSnrc Monte Carlo Code. The exposure of LiF:Mg,Ti in different phantom materials has been considered. Depending on the photon energy, SE represent 40%–90% of the total electron fluence (TEF) between 1 keV and 10 keV, being higher when the photon energy increases. Independent of the medium, versus mean photon energy displays a local minimum at around 40 keV, followed by a local maximum at ~80 keV–100 keV. The of SE generated by the x-ray beams are of order of 11 keV µm−1 to 19 keV µm−1 in LiF:Mg,Ti and 5 keV µm−1 to 9 keV µm−1 in liquid water which represent 3–5 times those produced by 60Co gamma rays in both media. These values were considerably greater than those of TEF, by factors of 3–8. Furthermore, of SE generated in liquid water by 20 kV–200 kV x-rays are similar to those of 76 MeV–120 MeV 3He ions. Contrary to the TEF, where were independent of the phantom material, at low photon energies of SE was found to be sensitive to the surrounding medium showing higher values within the phantom than in air. This result, which agrees with published experimental results, implies the importance of the SE ionization density for an understanding of dosimeter response induced by photon beams.

Analysis of the track- and dose-averaged LET and LET spectra in proton therapy using the geant4 Monte Carlo code.

The motivation of this study was to find and eliminate the cause of errors in dose-averaged linear energy transfer (LET) calculations from therapeutic protons in small targets, such as biological cell layers, calculated using the geant 4 Monte Carlo code. Furthermore, the purpose was also to provide a recommendation to select an appropriate LET quantity from geant 4 simulations to correlate with biological effectiveness of therapeutic protons. The authors developed a particle tracking step based strategy to calculate the average LET quantities (track-averaged LET, LETt and dose-averaged LET, LETd) using geant 4 for different tracking step size limits. A step size limit refers to the maximally allowable tracking step length. The authors investigated how the tracking step size limit influenced the calculated LETt and LETd of protons with six different step limits ranging from 1 to 500 μm in a water phantom irradiated by a 79.7-MeV clinical proton beam. In addition, the authors analyzed the detailed stochastic energy deposition information including fluence spectra and dose spectra of the energy-deposition-per-step of protons. As a reference, the authors also calculated the averaged LET and analyzed the LET spectra combining the Monte Carlo method and the deterministic method. Relative biological effectiveness (RBE) calculations were performed to illustrate the impact of different LET calculation methods on the RBE-weighted dose. Simulation results showed that the step limit effect was small for LETt but significant for LETd. This resulted from differences in the energy-deposition-per-step between the fluence spectra and dose spectra at different depths in the phantom. Using the Monte Carlo particle tracking method in geant 4 can result in incorrect LETd calculation results in the dose plateau region for small step limits. The erroneous LETd results can be attributed to the algorithm to determine fluctuations in energy deposition along the tracking step in geant 4. The incorrect LETd values lead to substantial differences in the calculated RBE. When the geant 4 particle tracking method is used to calculate the average LET values within targets with a small step limit, such as smaller than 500 μm, the authors recommend the use of LETt in the dose plateau region and LETd around the Bragg peak. For a large step limit, i.e., 500 μm, LETd is recommended along the whole Bragg curve. The transition point depends on beam parameters and can be found by determining the location where the gradient of the ratio of LETd and LETt becomes positive.

A Monte Carlo track structure simulation code for the full-slowing-down carbon projectiles of energies 1 keV u–1–10 MeV u–1 in water

The paper presents a new Monte Carlo track structure code (KURBUC_carbon) for simulations of full-slowing-down carbon projectiles C0–C6+ of energies 1 keV u–1–10 MeV u–1 in water vapour. The code facilitates investigation of the spatial resolution effect for scoring track parameters under the Bragg peak of a carbon ion beam. Interactions of carbon projectiles and secondary electrons were followed interaction-by-interaction down to a 1 keV u–1 cutoff for primary ions and down to 10 eV for electrons. Electronic interactions and nuclear elastic scattering were taken into account, including charge exchange reactions and double electronic interactions for the carbon projectiles. The reliability of the code was tested for radial dose, range and W-value. The calculated results were compared with the published experimental data and other model calculations. The results obtained showed good agreement in most cases where comparisons could be made. Depth dose profiles for 1–10 MeV u–1 C6+ were used to form a spread-out Bragg peak (SOBP) of 0.35 mm width in water. At all depths of the SOBP, the energy distributions of the carbon projectiles varied appreciably with the change in the scoring volume. The corresponding variation was nearly negligible for the track average linear energy transfer (LET), except at the distal end of the SOBP. By varying the scoring slab thickness from 1 to 100 µm, the maximum track average LET decreased by ∼30%. The Monte Carlo track structure simulation in the full-slowing-down mode is a powerful tool for investigation of the biophysical properties of radiation tracks under the Bragg peak and SOBP of a carbon ion beam. For estimation of radiation effectiveness under the Bragg peak the new Monte Carlo track structure code provides yet another accurate and effective dosimetry tool at a single cell level. This is because radiobiology within tissue elements can be understood better with dosimetry at cellular and subcellular level.

Present status and validation of HIBRAC

This paper describes in detail the latest version of HIBRAC, a computer code to calculate one-dimensional deterministic particle transport, designed for application in treatment-planning systems when using highly energetic ions for radiotherapy. HIBRAC can calculate dose, dose-average LET (Linear Energy Transfer), track-average LET, fluence and energy distributions as a function of the penetration depth of light ion beams in any solid and fluid target material. The validity of the code is verified against measured dose and fluence distributions. The code shows good agreement for all the systems studied.

Heavy Ion Radiolysis of Liquid Pyridine

The radiation chemical yields of the main products produced in liquid pyridine radiolysis (molecular hydrogen and dipyridyl) have been examined as a function of particle linear energy transfer (LET) with protons, helium ions, and carbon ions of a few to 30 MeV and compared to gamma-radiolysis published in a previous work (J. Phys. Chem. A 2005, 109, 461). Anthracene and biphenyl scavenging techniques have been used to clarify the role of the triplet excited state. An increase in triplet scavenger concentration leads to a decrease in pyridine triplet excited state with a concurrent decrease in dipyridyl, but formation of the latter does not primarily involve pyridyl radicals expected to be produced in the decomposition of the triplet excited state. A decrease in the yield of dipyridyl and an increase in molecular hydrogen are observed with increasing track average LET. The dipyridyl yield with 10 MeV carbon ions is 0.20 molecules/100 eV, which is only 16% of that of observed with gamma-rays. The low yield of dipyridyl with carbon ions is attributed to intratrack triplet-triplet (T-T) annihilation processes due to the increase in local triplet excited-state concentrations with increasing LET. An increasing yield of molecular hydrogen with increasing LET is probably due to an increase in the formation and subsequent decay of singlet excited states produced by the T-T annihilation. A complete mechanism for the radiolysis of liquid pyridine is presented.

Lethality of single-track events: comparison between calculations and experimental data

Recent results on cell killing by microbeams were analysed using three parameters (k,L,L1), where k is the mean number of lethal particles per cell nucleus, L [keV/mu m] is the track-average LET (linear energy transfer) in cells, and L 1[keV/ mu m] is a critical value for inducing lethal damage by a single track. Analysis showed that calculations are consistent with two data sets. The existence of a quadratic dependence on LET of cellular effects is confirmed in the high-LET region between 30 and 500keV/ mu m. L1~150keV/mu m was found to give the best fit and the sensitive area of the cell nucleus was determined as ~50 mu m2 for Chinese hamster V79 cells. In microbeam experiments with several MeV alpha-particles, the relationship between k and L for V79 cells can be expressed as L ~150(k)-1/2. For a given survival level, the difference in the required dose (or L) between the microbeam and broad-beam experiments is also analytically described.

Dose Conversion Factors and Linear Energy Transfer for Irradiation of Thin Blood Layers with Low-Energy X Rays

For irradiation of thin samples of biological material with low-energy X rays, conversion of measured air kerma, free in air to average absorbed dose to the sample is necessary. In the present paper, conversion factors from measured air kerma to average absorbed dose in thin blood samples are given for four low-energy X-ray qualities (14-50 kVp). These factors were obtained by Monte Carlo simulation of a practical sample holder. Data for different thicknesses of the blood and backing layer are presented. The conversion factors are found to depend strongly on the thicknesses of the blood layer and backing layer. In radiobiological work, knowledge of linear energy transfer (LET) values for the radiation quality used is often required. Track-averaged LET values for low-energy X rays are presented in this work. It is concluded that the thickness of the sample does not influence the LET value appreciably, indicating that for all radiobiological purposes this value can be regarded as a constant throughout the sample. Furthermore, the large difference between the LET value for a 50 kV spectrum found in this work and the value given in ICRU Report 16 is pointed out.

Characterization of fragmented heavy‐ion beams using a three‐stage telescope detector: Detector configuration and instrumentation

Accelerated heavy-ion beams used in biological and medical research are often utilized in conjunction with absorbers which lead to the fragmentation of the beam. The BERKLET, initially a two-stage solid-state telescope detector, was designed to make rapid, on-line energy and linear energy transfer (LET) measurements of individual particles in a heavy-ion beam, thus allowing characterization of fragmented beams. From data collected with the BERKLET, one is able to determine a number of important parameters. These include: residual energy and LET histograms for the full beam and for the individual Z components, relative number of particles with a given Z, and dose and track average LET's for the full beam and for the individual Z's. Improvements to the BERKLET design and changes in data analysis are discussed and contrasted with the results of an earlier BERKLET configuration. The most notable improvements are the addition of a thin scintillation detector for improved LET measurement, a tenfold improvement in the dynamic range of the event discriminator, reported here as 1:2000, and dual high-and low-gain amplification of the LET signals, permitting the identification of particles with Z's ranging from 12 down to 1.

The Irradiation of V79 Mammalian Cells by Protons with Energies below 2 MeV

The relative biological effectiveness (RBE) has been determined for protons with mean energies of 1.9, 1.15 and 0.76 MeV, from measurements of the survival of V79 Chinese hamster cells. The cells are supported as a monolayer and are swept through a beam of scattered protons produced using a 4 MeV Van de Graaff accelerator. An estimation of the dose and unrestricted linear energy transfer (LET) variation within the sensitive volume of the cells is given for the three proton energies. The RBEs for cell survival (relative to 250 kVp X-rays) at the 10 per cent survival level are 1.6, 1.9 and 3.36 for protons with track-average LETs of 17, 24 and 32 keV microns-1 respectively, and the data suggest that protons are most effective at about 40-50 keV microns-1. It is shown that the proton RBEs can be reconciled with those of other light ions if plotted against z*2/beta 2 (where z* is the effective charge and beta is the relative velocity) rather than against LET.