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Influence of the shielding on the induction of chromosomal aberrations in human lymphocytes exposed to high-energy iron ions.

Computer code calculations based on biophysical models are commonly used to evaluate the effectiveness of shielding in reducing the biological damage caused by cosmic radiation in space flights. Biological measurements are urgently needed to benchmark the codes. We have measured the induction of chromosomal aberrations in human peripheral blood lymphocytes exposed in vitro to 56Fe-ion beams accelerated at the HIMAC synchrotron in Chiba. Isolated lymphocytes were exposed to the 500 MeV/n iron beam (dose range 0.1-1 Gy) after traversal of 0 to 8 g/cm2 of either PMMA (lucite, a common plastic material) or aluminum. Three PMMA shield thickness and one Al shield thickness were used. For comparison, cells were exposed to 200 MeV/n iron ions and to X-rays. Chromosomes were prematurely condensed by a phosphatase inhibitor (calyculin A) to avoid cell-cycle selection produced by the exposure to high-LET heavy ion beams. Aberrations were scored in chromosomes 1, 2, and 4 following fluorescence in situ hybridization. The yield of chromosomal aberrations per unit dose at the sample position was poorly dependent on the shield thickness and material. However, the yield of aberrations per unit ion incident on the shield was increased by the shielding. This increase is associated to the increased dose-rate measured behind the shield as compared to the direct beam. These preliminary results prove that shielding can increase the effectiveness of heavy ions, and the damage is dependent upon shield thickness and material.

Adult↗

Biodosimetry of heavy ions by interphase chromosome painting.

We report measurements of chromosomal aberrations in peripheral blood lymphocytes from cancer patients undergoing radiotherapy treatment. Patients with cervix or esophageal cancer were treated with 10 MV X-rays produced at a LINAC accelerator, or high-energy carbon ions produced at the HIMAC accelerator at the National Institute for Radiological Sciences (NIRS) in Chiba. Blood samples were obtained before, during, and after the radiation treatment. Chromosomes were prematurely condensed by incubation in calyculin A. Aberrations in chromosomes 2 and 4 were scored after fluorescence in situ hybridization with whole-chromosome probes. Pre-treatment samples were exposed in vitro to X-rays, individual dose-response curves for the induction of chromosomal aberrations were determined, and used as calibration curves to calculate the effective whole-body dose absorbed during the treatment. This calculated dose, based on the calibration curve relative to the induction of reciprocal exchanges, has a sharp increase after the first few fractions of the treatment, then saturates at high doses. Although carbon ions are 2-3 times more effective than X-rays in tumor sterilization, the effective dose was similar to that of X-ray treatment. However, the frequency of complex-type chromosomal exchanges was much higher for patients treated with carbon ions than X-ray.

Aged↗

Photoneutrons from high energy medical linear accelerators: measurement of the spectrum and dose using a miniature proportional counter.

PURPOSE: A new method of measuring photoneutron dose to the patient during treatment with high energy photon or electron beams is presented. This method has the advantage of providing not only the dose, but the microdosimetric spectrum at the same time. METHODS AND MATERIALS: A miniature cylindrical gas proportional counter (0.5 mm diameter by 0.5 mm height) has been used to measure scatter radiation from a 20 MV teletherapy photon beam. At atmospheric pressure, filled with propane base tissue equivalent gas, this counter simulates a unit density tissue region of approximately 0.9 microns. We present here single event microdosimetric spectra measured outside the primary beam 1.4 m from the target. This technique allows a single measurement to determine the scattered dose due to gammas and photoneutron contamination, as well as the quality factor of the photoneutrons. RESULTS: Spectral components from scattered photons and the photoneutrons are easily separated, and dose contributions can be estimated. The ratio of photoneutron dose measured by the proportional counter to photon dose at isocenter is 0.75 x 10(-4). CONCLUSIONS: Neutron dose was also measured using a bubble neutrometer. The proportional counter and neutrometer agree within experimental errors. This type of instrument is shown to be a viable technique for determination of exposure of patient and also personnel to photoneutrons, providing not only a dose determination, but also a spectrum that can be used to estimate quality factors for equivalent dose. Its main drawback is that it requires a lengthy (several hours) measurement because of low count rate of the neutrons.

Humans↗

Physical aspects of a rotational total skin electron irradiation.

A technique for rotational total skin electron irradiation is presented in which the patient stands on a slowly rotating platform (SSD = 285 cm) in a large uniform linear accelerator electron field (Eo = 3.5 MeV). The beam is scattered by the transmission ionization chamber and by a special lead/aluminum scattering filter, and then degraded by a sheet of Lucite. A Farmer chamber is used as a patient dose monitor and a method for absolute dose calibration is presented. The field is uniform to within +/- 5% for dimensions of 180 X 40 cm2. The surface dose for rotational therapy is equal to 45% of the maximum dose in a stationary beam. The rotating beam exhibits a dose maximum on the surface, falls to 80% at 0.5 cm and has an x-ray contamination of approximately 4%. The surface dose rate is about 25 cGy/min for the rotating beam. The rotational beam percentage depth dose distributions, calculated using stationary beam information, agree well with measured data. The stationary beam exhibits a dose maximum at 4 mm in tissue, a surface dose of 93%, 80% dose at a depth of 1 cm, a practical range of 1.75 cm, and an x-ray contamination of 2.5%. The rotational total skin electron irradiation significantly reduces the patient treatment and setup time and solves the problem of beam matching, when compared to standard multiple-beam techniques.

Electrons↗

Combining multileaf fields to modulate fluence distributions.

PURPOSE: A method for modulating beam fluence from a linear accelerator is discussed. The beam modulation is accomplished remotely using a multileaf collimator and does not require entering the treatment room. METHODS AND MATERIALS: The multileaf collimator is used to define a series of field shapes that are superimposed at a fixed gantry angle to produce any desired fluence pattern. A heuristic technique for deriving the field shapes and corresponding monitor unit settings is described. The technique has been tested on randomly generated fluence distributions and on distributions with a limited number of peaks and valleys. The second type of distribution more closely simulates fluence patterns obtained with dose optimization software. Estimates of the time required to use this approach to treat a four-field plan are given and compared to the technique of placing a physical compensator in each beam. RESULTS: It has been demonstrated that complex fluence patterns within a 15 x 15 cm2 field can be achieved with less than 20 fields. Estimates show that this technique is faster than entering the treatment room to change physical compensators. Some limitations of the method are discussed. CONCLUSION: Optimized distributions that conform the dose to irregularly shaped target volumes that wrap around critical structures are possible using superimposed multileaf fields. A method for defining the field shapes is presented.

Humans↗

Radiation myelopathy in over-irradiated patients: MR imaging findings.

The objective of this work is to report the MRI findings in patients with radiation myelopathy due to accidental local over-irradiation syndrome. Eight patients (seven males and one female) were suffering from over-irradiation syndrome as a result of treatments from a malfunctioning linear electron accelerator. The mean accidental estimated dose was 136 Gy delivered to the "open-neck" (seven cases) and to the thoracic wall (one case), during a mean of 5.4 sessions (range 1-9 sessions). Paresthesia and weakness in the upper extremities were the earliest symptoms (87.5 %), with evolution to paralysis in all patients. No patient is alive (mean survival time 64 days). In all cases MRI was negative for neurologic lesions in the acute phase ( < 90 days from irradiation; Radiation Therapy Oncology Group scoring system). Late signs of radiation myelitis manifested as high-intensity signals on T2-weighted images in three patients, and as Gd-DTPA enhancement of T1-weighted images in one case. Autopsies performed on four patients who died in acute phase showed morphologic alterations in white matter: edema in 75 %, and necrosis and glial reaction as well as obliterative vasculitis in all cases. In cases of over-irradiation, MRI may be normal in acute phase even if the patients have severe neurologic deficit, as positive MRI findings appear only in delayed radiation myelitis.

Adult↗

[Stereotactic irradiation for brain metastases using linear accelerator].

A stereotactic irradiation (STI) system using a linear accelerator was developed and its effectiveness for brain metastasis was investigated. The system consisted of a conventional linear accelerator, invasive fixation head frame (RADFRAME, Mizuho Ika Kogyo), and a tungsten collimator. The RADFRAME was developed to be used with any linear accelerators and with any dose planning systems. The accuracy of the irradiation was assured to be within +/-1.5mm. Fifty-one patients with metastatic brain tumors were treated using the system. The overall median survival time was 10 months. No difference in survival was observed between patients with a single lesion and patients with two or three lesions. Complete, partial, and minimal responses were obtained in 16 (39%), 18 (41%), and 7 (16%) lesions. These were comparable to the reported results of gamma knife treatment. A maximum dose of 25 Gy was suggested to be more effective than lower doses. Local control rate was higher in tumors with a diameter of less than 2.0cm (87.5%) than in larger tumors (60%). No difference in tumor response was observed among various histopathologic types. In a patient with a 25mm cerebellar metastasis from an adenocarcinoma of the lung, autopsy at 5 months after STI showed fibrinoid degeneration and hyaline deposition without residual tumor at the Gd-enhanced region on MRI. The efficacy of linac stereotactic irradiation was equal to that of gamma knife radiotherapy for metastatic brain tumors.

Adenocarcinoma↗

Rejoining of DNA double-strand breaks induced by accelerated nitrogen ions.

Rejoining of radiation-induced DNA double-strand breaks (dsb) was measured in cultured cells with pulsed-field gel electrophoresis after radiation doses in the range of 5-30 Gy. Human glioma, U-343MG and Chinese hamster, V79, cells were irradiated with either accelerated nitrogen ions of high linear energy transfer, LET approximately 125 keV/ microns, or photons from 60Co. The induction frequencies of dsb were similar for the two radiation qualities with a relative biological effectiveness, RBE, of 0.90 and 0.89 for the human and hamster cell lines respectively. The biphasic rejoining kinetics differed significantly between the two radiation qualities when studied in the human glioma cells. The difference was seen within the first hour after irradiation and after 6 h there were considerable differences in both the total amount of unrejoined dsb and the fraction of dsb rejoined during the slow phase. When rejoining was analysed 20-22 h after irradiation, the nitrogen ions gave 2.5-2.9 times more residual dsb than the gamma photons. The results for the hamster V79 cells were, up to 2h after irradiation, similar, but the difference between the two radiation qualities was less accentuated. In summary, similar initial yields of dsb after exposure of cells to high or low LET resulted in both radiation quality and cell type-dependent differences when the rejoining of these breaks were compared.

Animals↗

Electron beam therapy at extended SSDs: an analysis of output correction factors for a Mitsubishi linear accelerator.

The effects of extended source-to-surface distance (SSD) on the electron beam dose profiles were evaluated for various electron beam energies--6, 9, 12, 15 and 20 MeV-and the accuracy of various output correction methods was analysed on a Mitsubishi linear accelerator using a radiation field analyser (RFA). The dose fall-off region of the central axis depth-dose curves was nearly independent for SSDs up to 120 cm where as in the build-up region, a marginal reduction of surface dose was observed, particularly for lower energies and for smaller field sizes. Effective SSDs and virtual source distances were evaluated for field sizes ranging from 5 x 5 to 15 x 15 cm2 for various energies. Curve fitting was done with the measured outputs with various equations and coefficients were evaluated. The accuracy of the derived output correction factors by effective SSD, virtual source distance and curve-fit methods was assessed by evaluating correlation coefficients between the calculated and the measured values. The correlation coefficient was best with the linear-quadratic equation followed by the effective SSD method and the virtual source method. The output correction based on the linear-quadratic equation showed the best estimate of electron beam output at extended SSDs with an accuracy well within +/- 1%. The rapid reduction of dose due to the applicator-scattered component at d(max) point with an extended SSD was significant for the 5 x 5 cm2 applicator and lower energies.

Algorithms↗

Dynamic arc radiosurgery and radiotherapy: commissioning and verification of dose distributions.

PURPOSE: Conformal stereotactic radiosurgery and radiotherapy using a linear accelerator and a micromultileaf collimator (mMLC) offer the possibility of irradiating irregularly shaped target volumes. Dynamic arc radiosurgery and radiotherapy, i.e., stereotactic radiation therapy combining a moving gantry with a dynamic mMLC, enable the radiation even of lesions with concave structures. METHODS AND MATERIALS: The dynamic arc method requires additional tools for quality assurance (QA) and three-dimensional verification at a high spatial resolution. A QA program was developed. Dose distributions of planning target volumes with concavities were investigated in polymer gel phantoms. The radiation-induced change of the relaxation rate R(2) was measured by magnetic resonance imaging. The distributions were compared with image processing tools. RESULTS: Using the therapy-planning software BrainSCAN 4.0 (and 4.1 beta) in combination with the mMLC m3, deviations between the planned and measured 90% isodoses of about 2 mm were registered in the isocenter plane. Three-dimensional verification was feasible in the range of accuracy achieved in planning and dose measurement. CONCLUSIONS: Dynamic arc radiosurgery and radiotherapy offer excellent conformation even for complicated planning target volumes with concavities. The dose distribution calculated with the treatment-planning software used can be accomplished with the available equipment. Patients can be treated by dynamic arc radiosurgery and radiotherapy.

Calibration↗

Photon beam characterization and modelling for Monte Carlo treatment planning.

Photon beams of 4, 6 and 15 MV from Varian Clinac 2100C and 2300C/D accelerators were simulated using the EGS4/BEAM code system. The accelerators were modelled as a combination of component modules (CMs) consisting of a target, primary collimator, exit window, flattening filter, monitor chamber, secondary collimator, ring collimator, photon jaws and protection window. A full phase space file was scored directly above the upper photon jaws and analysed using beam data processing software, BEAMDP, to derive the beam characteristics, such as planar fluence, angular distribution, energy spectrum and the fractional contributions of each individual CM. A multiple-source model has been further developed to reconstruct the original phase space. Separate sources were created with accurate source intensity, energy, fluence and angular distributions for the target, primary collimator and flattening filter. Good agreement (within 2%) between the Monte Carlo calculations with the source model and those with the original phase space was achieved in the dose distributions for field sizes of 4 cm x 4 cm to 40 cm x 40 cm at source surface distances (SSDs) of 80-120 cm. The dose distributions in lung and bone heterogeneous phantoms have also been found to be in good agreement (within 2%) for 4, 6 and 15 MV photon beams for various field sizes between the Monte Carlo calculations with the source model and those with the original phase space.

Models, Theoretical↗

Practical aspects of in situ 16O (gamma,n) 15O activation using a conventional medical accelerator for the purpose of perfusion imaging.

We report investigations into the feasibility of generating radioactive oxygen (15O, a positron emitter, with half-life 2.05 min) using a tuned Elekta SL25 accelerator, for the end purpose of imaging tumor perfusion. 15O is produced by the "gamma, neutron," (gamma,n) reaction between high-energy photons and normal oxygen (16O) in the body. As most in vivo 16O is bound in water molecules the 15O radio-marker is produced in proportion to water content in tissue. Imaging the washout of the 15O distribution using sensitive positron-emission-tomography (PET) technology can yield spatial information about blood perfusion in the tissue. The aim of this article was to determine the amount of 15O activity that could be produced by the tuned medical accelerator. A further aim was to model the activation process using Monte Carlo and to investigate ways to optimize the amount of 15O that could be generated. Increased activation was achieved by (i) tuning the beam to give higher-energy electrons incident on the target of the accelerator, (ii) increasing dose rate by removing the conventional filtration in the beam and reducing the source to object distance, and (iii) reducing low-energy photons by means of a carbon block absorber. The activity per-unit-dose produced by the tuned beam was measured by irradiating spheres of water to known doses and placing the spheres in a calibrated coincidence-counting apparatus. Peak energy of the tuned bremsstrahlung beam was estimated at 29 MeV, and generated activity up to 0.24/microCi/cc/3Gy in water. The measured amount of 15O agreed to within 10% of the prediction from the Monte-Carlo-computed spectrum, indicating reasonable ability to model the activation process. The optimal thickness of the carbon absorber was found to be about 25 cm. The insertion of a carbon absorber improved spectral quality for activation purposes but at the cost of reduced dose rate. In conclusion, the viability of generating 15O with an Elekta SL25 has been demonstrated. In conjunction with recent advances in high-sensitivity portable PET imaging devices, real potential exists for imaging in situ activated 15O washout as a surrogate measurement of macroscopic tumor perfusion.

Calibration↗

A large-area ionization chamber for portal image calibration.

Methods of removing the effects of linear accelerator (linac) output fluctuation from electronic portal images are described and compared. The output of the linac is measured using a specially constructed large-area ionization chamber during imaging and recorded with the image. The use of a dose-rate signal directly from the linac monitor chamber is discussed. Various versions of a quadratic thickness calibration scheme are tested, incorporating linac output data measured by the ionization chamber. Experimental results are presented showing that the incorporation of data from the ionization chamber gives improved absolute calibration accuracy and flatness. Immediately after calibration, the mean systematic thickness error in calibration of a uniform 136.8 mm water-equivalent slab was shown to be no more than 0.6 mm with a thickness variation within each image also of no more than +/-0.8 mm. This was true even when imaging with an unstable linac beam giving mean thickness errors between images of 8.8 mm and variations within each image of +/-4.9 mm without the ionization chamber correction. Up to one month after calibration, use of the ionization chamber to remove short-term linac fluctuations is shown to still keep mean thickness errors to less than 1.6 mm with variations within each image of no more than +/-1.4 mm.

Calibration↗

Monte Carlo simulation of MOSFET detectors for high-energy photon beams using the PENELOPE code.

The aim of this work was the Monte Carlo (MC) simulation of the response of commercially available dosimeters based on metal oxide semiconductor field effect transistors (MOSFETs) for radiotherapeutic photon beams using the PENELOPE code. The studied Thomson&Nielsen TN-502-RD MOSFETs have a very small sensitive area of 0.04 mm(2) and a thickness of 0.5 microm which is placed on a flat kapton base and covered by a rounded layer of black epoxy resin. The influence of different metallic and Plastic water build-up caps, together with the orientation of the detector have been investigated for the specific application of MOSFET detectors for entrance in vivo dosimetry. Additionally, the energy dependence of MOSFET detectors for different high-energy photon beams (with energy >1.25 MeV) has been calculated. Calculations were carried out for simulated 6 MV and 18 MV x-ray beams generated by a Varian Clinac 1800 linear accelerator, a Co-60 photon beam from a Theratron 780 unit, and monoenergetic photon beams ranging from 2 MeV to 10 MeV. The results of the validation of the simulated photon beams show that the average difference between MC results and reference data is negligible, within 0.3%. MC simulated results of the effect of the build-up caps on the MOSFET response are in good agreement with experimental measurements, within the uncertainties. In particular, for the 18 MV photon beam the response of the detectors under a tungsten cap is 48% higher than for a 2 cm Plastic water cap and approximately 26% higher when a brass cap is used. This effect is demonstrated to be caused by positron production in the build-up caps of higher atomic number. This work also shows that the MOSFET detectors produce a higher signal when their rounded side is facing the beam (up to 6%) and that there is a significant variation (up to 50%) in the response of the MOSFET for photon energies in the studied energy range. All the results have shown that the PENELOPE code system can successfully reproduce the response of a detector with such a small active area.

Algorithms↗

Calculation of 10 MV x-ray spectra emitted by a medical linear accelerator using the BFGS quasi-Newton method.

To calculate photon spectra for a 10 MV x-ray beam emitted by a medical linear accelerator, we performed numerical analysis using the aluminium transmission data obtained along the central axis of the beam under the narrow beam condition corresponding to a 3x3 cm2 field at a 100 cm distance from the source. We used the BFGS quasi-Newton method based on a general nonlinear optimization technique for the numerical analysis. The attenuation coefficients, aluminium thicknesses and measured transmission data are necessary inputs for the numerical analysis. The calculated x-ray spectrum shape was smooth in the lower to higher energy regions without any angular components. The x-ray spectrum acquired by the employed method was evaluated by comparing the measurements along the central axis percentage depth dose in a water phantom and by a Monte Carlo simulation code, the electron gamma shower code. The values of the calculated percentage depth doses for a 10x10 cm2 field at a 100 cm source-to-surface distance in a water phantom were obtained using the same geometry settings as those of the water phantom measurement. The differences in the measured and calculated values were less than +/-1.0% for a broad region from the shallow part near the surface to deep parts of up to 25 cm in the water phantom.

Aluminum↗

Gamma ray nuclear resonance absorption: an alternative method for in vivo body composition studies.

We have evaluated gamma ray nuclear resonance absorption (gamma-NRA) on nitrogen, a mature technology proposed and developed by Soreq NRC for detecting explosives, as an alternative to neutron activation for in vivo assaying of body nitrogen. The principles of the gamma-NRA method are outlined, and a test facility constructed at McMaster University's Accelerator Laboratory is described. The results of a feasibility study recently performed there on phantoms and animal tissue are presented and discussed. gamma-NRA is a full imaging technique that essentially constitutes element-specific absorptiometry--i.e., it can generate projections of the mass distribution for a specific element, along with a conventional radiograph of the patient. From the transmission profile of an individual scanned by 9.17 MeV gamma rays, local or whole body nitrogen content can be determined via the resonant attenuation undergone when the beam encounters regions of nitrogen concentration. The advantages of gamma-NRA over neutron activation are (a) radiation doses delivered to the body are at least one order of magnitude lower, thus allowing repeated measurements on individual patients and also rendering the method ethically acceptable for application to children; (b) gamma-NRA is inherently free from uncertainties related to nonuniform distributions of the element in question within the body; (c) it is applicable to patients of varying size and shape; and (d) it yields both nitrogen images and conventional radiographic images of the body.

Animals↗

Quality control of measured x-ray beam data.

The purpose of this study was to examine whether the quality of measured x-ray beam data can be judged from how well the data agree with a semiempirical formula. Tissue-phantom ratios (TPR) and output factors for several accelerators in the energy range 4-25 MV were fitted to the formula, separating the dose contributions from primary and phantom-scattered photons. The former was described by exponential attenuation in water, with beam hardening, and the latter by the scatter-to-primary dose ratio using two parameters related to the probability and the directional distribution of the scattered photons. Electron disequilibrium was not considered. Two approaches were evaluated. In one, the attenuation and hardening coefficients were determined from measurements in a narrow-beam geometry; in the other, they were extracted by the fitting procedure. Measured and fitted data agreed within +/- 2% in both cases. The differences were randomly distributed and had a standard deviation of typically 0.7%. Singular points with errors were easily identified. Systematic errors were revealed by increased standard deviation. However, when the attenuation was derived by the fitting algorithm, the attenuation coefficient deviated significantly from the experimental value. It is concluded that the semiempirical formula can serve to evaluate and verify beam data measured in water and that the physically most accurate description requires that the attenuation and hardening coefficients be determined in a narrow-beam geometry. The attenuation coefficient is an excellent measure of both the primary and the scatter dose component, i.e., of beam quality.

Biophysical Phenomena↗

[Experimental study on the prevention and treatment of radiation lung injury by blood-activating and stasis-dissipating drugs].

OBJECTIVE: To observe the pathological changes and the expression of tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) in lung tissue of rats with radiation injury for exploring the mechanism of blood-activating and stasis-dissipating drugs in radiation injury prevention and treatment. METHODS: One hundred and thirty SD female rats were randomly allocated into the simple irradiation group (n=60), the TCM herbs treatment group (n=60) and the blank control group (n=10). The right lung of all rats except those in the blank control group were irradiated by linear accelerator, 3 Gy each time, twice weekly, the maximum accumulated dose being 30 Gy. Ten rats in the two groups were randomly sacrificed at each of the 6 time points (1, 3, 5, 8, 12 and 26 weeks after repeated irradiation), their lung was harvested out, sliced and dyed with HE stain. The histological changes, levels of TNF-alpha and TGF-beta expression in the lung tissue were then observed by immunohistochemical technique. RESULTS: The most serious acute radiation pneumonia was seen in the 5th week and pulmonary fibrosis was remarkable in the 26th week in the simple irradiation group, with the expressions of TNF-alpha and TGF-beta at different time phases enhanced significantly (P < 0.01). While in the TCM herbs treatment group, the pneumonia was milder, pulmonary fibrosis in late stage was not so obvious, and the expressions of TNF-alpha and TGF-beta significantly lower than those in the simple irradiation group (P < 0.01). CONCLUSION: Blood-activating and stasis-dissipating drugs can inhibit expression of inflammation-inducing factors and fibrosis-inducing factors to lessen the inflammatory reaction of early radiation pneumonia, prolong the progression of radiation lung fibrosis, showing preventive and treating action on radiation lung injury.

Animals↗

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